Limited evidence indicates that the use of  combined oral contraceptives  is associated with a reduced risk of endometriosis, as is regular exercise and the avoidance of alcohol and caffeine. [ 3 ]  There is little known information on preventing endometriosis. [ 129 ]


While there is no cure for endometriosis, there are treatments for pain and endometriosis-associated infertility. [ 130 ]  Pain can be treated with hormones, painkillers or, in severe cases, surgery. [ 131 ]


In most cases, the symptoms disappear or improve with menopause (natural or surgical). [ 132 ]  In the reproductive years, endometriosis is merely managed: the goal is to provide pain relief, to restrict progression of the process, and to restore or preserve fertility where needed. In younger individuals, some surgical treatment attempts to remove endometriotic tissue and preserve the ovaries without damaging normal tissue. [ 17 ] [ 133 ]


Pharmacotherapy for pain management can be initiated based on the presence of symptoms and examination and ultrasound findings that rule out other potential causes. [ 134 ]


In general, the diagnosis of endometriosis is confirmed during surgery, at which time removal can be performed. Further steps depend on circumstances: someone without infertility can manage symptoms with pain medication and hormonal medication that suppresses the natural cycle, while an infertile individual may be treated expectantly after surgery, with fertility medication, or with  in vitro fertilisation  (IVF).


A 2020 Cochrane systematic review found that for all types of endometriosis, "it is uncertain whether laparoscopic surgery improves overall pain compared to diagnostic laparoscopy". [ 135 ]


Based on strong evidence, experts recommend that surgery be performed laparoscopically (through keyhole surgery) rather than open. [ 113 ]  Treatment consists of the ablation or excision of the endometriosis,  electrocoagulation , [ 136 ]  lysis of adhesions, resection of endometriomas, and restoration of normal pelvic anatomy as much as is possible. [ 113 ] [ 137 ]  When laparoscopic surgery is used, small instruments are inserted through the incisions to remove the endometriosis tissue and adhesions. Because the incisions are very small, there will only be small scars on the skin after the procedure, and most individuals recover from surgery quickly and have a reduced risk of adhesions. [ 138 ]  Many endometriosis specialists believe that excision is the ideal surgical method to treat endometriosis. [ 139 ]  A 2017 literature review found excision improved some outcomes over ablation. [ 140 ]  In the United States, some specialists trained in excision for endometriosis do not accept health insurance, because insurance companies do not reimburse the higher costs of this procedure over ablation. [ 141 ]


As for deep endometriosis, a  segmental resection  or shaving of nodules is effective but is associated with an increased rate of complications, of which about 4.6% are major. [ 142 ]


Historically, a  hysterectomy  (removal of the uterus) was thought to be a cure for endometriosis in individuals who do not wish to conceive. Removal of the uterus may be beneficial as part of the treatment, if the uterus itself is affected by adenomyosis. However, this should only be done in combination with removal of the endometriosis by excision. If endometriosis is not also removed at the time of hysterectomy, pain may persist. [ 113 ]  A study of hysterectomy patients found those with endometriosis were not using less pain medication 3 years after the procedure. [ 143 ]


Presacral neurectomy  may be performed where the nerves to the uterus are cut. However, this technique is not usually used due to the high incidence of associated complications including presacral hematoma and irreversible problems with urination and constipation. [ 113 ]


The underlying process that causes endometriosis may not cease after a surgical or medical intervention. Even though surgery can improve symptoms, the resurgence of pain is common. [ 144 ]  A study has shown that dysmenorrhea recurs at a rate of 30 percent within a year following laparoscopic surgery. Resurgence of lesions tend to appear in the same location if the lesions were not completely removed during surgery. It has been shown that laser ablation resulted in higher and earlier recurrence rates when compared with endometrioma cystectomy; and recurrence after repetitive laparoscopy was similar to that after the first surgery. Endometriosis has a 10% recurrence rate after hysterectomy and bilateral salpingo-oophorectomy. [ 145 ]


Endometriosis recurrence following conservative surgery is estimated as 21.5% at 2 years and 40-50% at 5 years. [ 146 ]


Recurrence rate for DIE after surgery is less than 1%. [ 147 ]


Risk of developing complications following surgery depend on the type of the lesion that has undergone surgery. [ 136 ]  55% to 100% of individuals develop adhesions following pelvic surgery, [ 148 ]  which can result in infertility, chronic abdominal and pelvic pain, and difficult reoperative surgery. Trehan's temporary ovarian suspension, a technique in which the ovaries are suspended for a week after surgery, may be used to reduce the incidence of adhesions after endometriosis surgery. [ 149 ] [ 150 ]  Removal of cysts on the ovary without removing the ovary is a safe procedure. [ 136 ]


The overall effectiveness of manual physical therapy to treat endometriosis has not yet been identified. [ 173 ]


A 2021 meta-analysis found that GnRH analogues and combined hormonal contraceptives were the best treatment for reducing dyspareunia, menstrual and non menstrual pelvic pain. [ 174 ]  A 2018 Swedish systematic review found a large number of studies but a general lack of scientific evidence for most treatments. [ 117 ]  There was only one study of sufficient quality and relevance comparing the effect of surgery and non-surgery. [ 175 ]  Cohort studies indicate that surgery is effective in decreasing pain. [ 175 ]  Most complications occurred in cases of low intestinal anastomosis, while risk of fistula occurred in cases of combined abdominal or vaginal surgery, and urinary tract problems were common in intestinal surgery. [ 175 ]  The evidence was found to be insufficient regarding surgical intervention. [ 175 ]


The advantages of physical therapy techniques are decreased cost, absence of major side-effects, it does not interfere with fertility, and near-universal increase of sexual function. [ 176 ]  Disadvantages are that there are no large or long-term studies of its use for treating pain or infertility related to endometriosis. [ 176 ]


Surgery is more effective than medicinal intervention for addressing infertility associated with endometriosis. [ 133 ]  Surgery attempts to remove endometrium-like tissue [ 17 ]  and preserve the ovaries without damaging normal tissue. [ 133 ]  Receiving hormonal suppression therapy after surgery might be positive regarding endometriosis recurrence and pregnancy. [ 177 ]  In-vitro fertilization (IVF) procedures are effective in improving fertility in many individuals with endometriosis. [ 1 ]


During fertility treatment, the ultralong pretreatment with GnRH-agonist has a higher chance of resulting in pregnancy for individuals with endometriosis, compared to the short pretreatment. [ 117 ]


Determining how many people have endometriosis is challenging because definitive diagnosis requires surgical visualization through laparoscopic surgery. [ 178 ]  Criteria that are commonly used to establish a diagnosis include pelvic pain, infertility, surgical assessment, and in some cases, magnetic resonance imaging. An ultrasound can identify large clumps of tissue as potential endometriosis lesions and ovarian cysts but it is not effective for all patients, especially in cases with smaller, superficial lesions. [ 179 ]


Ethnic differences in endometriosis have been observed. The condition is more common in women of  East Asian  and  Southeast Asian  descent than in White women. [ 17 ]  Risk factors include having a family history of the condition. [ 18 ]


One estimate is that 10.8 million people are affected globally as of 2015 [update] . [ 6 ]  Other sources estimate 6 to 10% of the general female population [ 1 ]  and 2 to 11% of asymptomatic women [ 17 ]  are affected. In addition, 11% of women in a general population have undiagnosed endometriosis that can be seen on magnetic resonance imaging (MRI). [ 180 ] [ 178 ]  Endometriosis is most common in those in their thirties and forties; however, it can begin in girls as early as eight years old. [ 3 ] [ 4 ]  It results in few deaths with unadjusted and age-standardized death rates of 0.1 and 0.0 per 100,000. [ 6 ]  Endometriosis was first determined to be a separate condition in the 1920s. [ 181 ]  Before that time, endometriosis and  adenomyosis  were considered together. [ 181 ]  It is unclear who first described the disease.


It chiefly affects adults from premenarche to postmenopause, regardless of race or ethnicity or whether or not they have had children and is estimated to affect over 190 million women in their reproductive years. [ 182 ]  Incidences of endometriosis have occurred in postmenopausal individuals, [ 183 ]  and in less common cases, individuals may have had endometriosis symptoms before they even reach menarche. [ 184 ] [ 80 ]


The rate of recurrence of endometriosis is estimated to be 40-50% for adults over a 5-year period. [ 185 ]  The rate of recurrence has been shown to increase with time from surgery and is not associated with the stage of the disease, initial site, surgical method used, or post-surgical treatment. [ 185 ]


Endometriosis was first discovered microscopically by  Karl von Rokitansky  in 1860, [ 186 ]  although the earliest antecedents may have stemmed from concepts published almost 4,000 years ago. [ 187 ]  The  Hippocratic Corpus  outlines symptoms similar to endometriosis, including uterine ulcers, adhesions, and infertility. [ 187 ]  Historically, women with these symptoms were treated with  leeches ,  straitjackets ,  bloodletting , chemical  douches ,  genital mutilation , pregnancy (as a form of treatment), hanging upside down, surgical intervention, and even killing due to suspicion of  demonic possession . [ 187 ]  Hippocratic doctors recognized and treated chronic pelvic pain as a true organic disorder 2,500 years ago, but during the Middle Ages, there was a shift into believing that women with pelvic pain were mad, immoral, imagining the pain, or simply misbehaving. [ 187 ]  The symptoms of inexplicable chronic pelvic pain were often attributed to imagined madness, female weakness, promiscuity, or  hysteria . [ 187 ]  The historical diagnosis of hysteria, which was thought to be a psychological disease, may have indeed been endometriosis. [ 187 ]  The idea that chronic pelvic pain was related to mental illness influenced modern attitudes regarding individuals with endometriosis, leading to delays in correct diagnosis and indifference to the patients' true pain throughout the 20th and into the 21st century. [ 187 ]


Hippocratic doctors believed that delaying childbearing could trigger diseases of the uterus, which caused endometriosis-like symptoms. Women with dysmenorrhea were encouraged to marry and have children at a young age. [ 187 ]  The fact that Hippocratics were recommending changes in marriage practices due to an endometriosis-like illness implies that this disease was likely common, with rates higher than the 5-15% prevalence that is often cited today. [ 187 ]  If indeed this disorder was so common historically, this may point away from modern theories that suggest links between endometriosis and dioxins,  PCBs , and chemicals. [ 187 ]


The early treatment of endometriosis was  surgical  and included  oophorectomy  (removal of the ovaries) and hysterectomy (removal of the uterus). [ 188 ]  In the 1940s, the only available hormonal therapies for endometriosis were high-dose  testosterone  and  high-dose estrogen  therapy. [ 189 ]  High-dose estrogen therapy with  diethylstilbestrol  for endometriosis was first reported by Karnaky in 1948 and was the main  pharmacological  treatment for the condition in the early 1950s. [ 190 ] [ 191 ] [ 192 ]   Pseudopregnancy  (high-dose estrogen–progestogen therapy) for endometriosis was first described by Kistner in the late 1950s. [ 190 ] [ 191 ]  Pseudopregnancy as well as progestogen monotherapy dominated the treatment of endometriosis in the 1960s and 1970s. [ 192 ]  These agents, although efficacious, were associated with intolerable side effects.  Danazol  was first described for endometriosis in 1971 and became the main therapy in the 1970s and 1980s. [ 190 ] [ 191 ] [ 192 ]  In the 1980s  GnRH agonists  gained prominence for the treatment of endometriosis and by the 1990s had become the most widely used therapy. [ 191 ] [ 192 ]  Oral GnRH antagonists such as  elagolix  were introduced for the treatment of endometriosis in 2018. [ 193 ]


A number of public figures have spoken about their experience with endometriosis, including:


The economic burden of endometriosis is widespread and multifaceted. [ 236 ]  Endometriosis is a chronic disease that has direct and indirect costs which include loss of work days, direct costs of treatment, symptom management, and treatment of other associated conditions such as depression or chronic pain. [ 236 ]  One factor which seems to be associated with especially high costs is the delay between onset of symptoms and diagnosis.


Costs vary greatly between countries. [ 237 ]  Two factors that contribute to the economic burden include healthcare costs and losses in productivity. A Swedish study of 400 endometriosis patients found "Absence from work was reported by 32% of the women, while 36% reported reduced time at work because of endometriosis". [ 238 ]  An additional cross sectional study with Puerto Rican women, "found that endometriosis-related and coexisting symptoms disrupted all aspects of women's daily lives, including physical limitations that affected doing household chores and paid employment. The majority of women (85%) experienced a decrease in the quality of their work; 20% reported being unable to work because of pain, and over two-thirds of the sample continued to work despite their pain." [ 239 ]


There are a number of barriers that those affected face to receiving diagnosis and treatment for endometriosis. Some of these include outdated standards for laparoscopic evaluation, stigma about discussing menstruation and sex, lack of understanding of the disease, primary-care physicians' lack of knowledge, and assumptions about typical menstrual pain. [ 240 ]  On average, those later diagnosed with endometriosis waited 2.3 years after the onset of symptoms before seeking treatment and nearly three quarters of women receive a misdiagnosis prior to endometriosis. [ 241 ]  Self-help groups say practitioners delay making the diagnosis, often because they do not consider it a possibility. There is a typical delay of 7–12 years from symptom onset in affected individuals to professional diagnosis. [ 242 ]  There is a general lack of knowledge about endometriosis among primary care physicians. Half of general health care providers surveyed in a 2013 study were unable to name three symptoms of endometriosis. [ 243 ]  Health care providers are also likely to dismiss described symptoms as normal menstruation. [ 244 ]  Younger patients may also feel uncomfortable discussing symptoms with a physician. [ 244 ]


Race and ethnicity may play a role in how endometriosis affects one's life. Endometriosis is less thoroughly studied among Black people, and the research that has been done is outdated. [ 245 ]
 [ 246 ]
Cultural differences among ethnic groups also contribute to attitudes toward and treatment of endometriosis, especially in Hispanic or Latino communities. A study done in Puerto Rico in 2020 found that health care and interactions with friends and family related to discussing endometriosis were affected by stigma. [ 247 ]  The most common finding was a referral to those expressing pain related to endometriosis as "changuería" or "changas", terms used in Puerto Rico to describe pointless whining and complaining, often directed at children. [ 247 ]


The existing stigma surrounding women's health, specifically endometriosis, can lead to patients not seeking diagnoses, lower quality of healthcare, increased barriers to care and treatment, and negative reception from members of society. [ 248 ]  Additionally,  menstrual stigma  significantly contributes to the broader issue of endometriosis stigma, creating an interconnected challenge that extends beyond reproductive health. [ 249 ] [ 250 ]
Widespread  awareness campaigns , developments and implementations aimed to multilevel anti-stigma organizational and structural changes, as well as more qualitative studies of the endometriosis stigma, help to overcome the harm of the phenomenon. [ 251 ]


Preliminary research on mouse models showed that monoclonal antibodies, as well as inhibitors of  MyD88  downstream signaling pathway, can reduce lesion volume. Thanks to that, clinical trials are being done on using a monoclonal antibody directed against IL-33 and using  anakinra , an IL-1 receptor antagonist. [ 172 ]


Taking the contraceptive pills or getting long-acting progestogen injections seems to be equally effective for preventing recurring pain after endometriosis surgery. Compared to taking the pill, progestogen might result in reduced risk of needing further treatments or surgery. [ 144 ] [ 252 ]


Clinical trials are exploring the potential benefits of cannabinoid extracts,  dichloroacetic acid  and  curcuma  capsules. [ 172 ]


This article incorporates text in the  public domain  as a Swedish government "utterance" by  URL§9


Flo  is a health  app  that provides  menstrual cycle  and  ovulation  tracking. [ 1 ]


The application is available on  iOS  and  Android . [ 2 ]  Application's development hubs are in  London ,  Amsterdam  and  Vilnius . [ 3 ] [ 4 ]  Flo has over 350 million downloads worldwide and 60 million monthly active users as of February 2024. [ 5 ]  In mid-2024, it reached  unicorn  status. [ 6 ]


Flo was co-founded in 2015 by Dmitry and  Yuri Gurski , in  Belarus . [ 7 ]  Dmitry serves as the company's CEO. [ 8 ]


In 2016, the company raised $1 million in seed round funding from Flint Capital and Haxus Venture Fund. [ 9 ]


In 2017, Flo received an investment of $5 million from Flint Capital and model  Natalia Vodianova . [ 7 ]  Vodianova also helped develop Flo's "Let’s Talk About it. Period" worldwide awareness campaign. [ 10 ]  In December of that year, Flo began working with the  United Nations Population Fund  (UNFPA) to spread awareness about women's reproductive and sexual health issues. [ 11 ]  Also in 2017, Flo launched a question and answer service within the app. [ 7 ]


In 2018, Flo received an investment of $6 million from Mangrove Capital Partners, with participation from Flint Capital and Haxus, giving the company a valuation of $200 million. [ 12 ]


In mid-2019, Flo received an additional investment of $7.5 million.  Founders Fund  was one of the main investors in the round. [ 13 ]  In September 2019, Privacy International published a report regarding data sharing for a number of period-tracking  apps . [ 14 ]  Following a number of data-sharing controversies in the industry, Flo and four other  apps  implemented measures to protect user's data from third parties. [ 15 ]


In early September 2021, Flo announced it closed $50M in a Series B financing, bringing the total capital raised to $65 million and company valuation to $800M. [ 16 ]  VNV Global and Target Global both led the round. [ 17 ]


Flo was initially created as a period and  ovulation  tracking application, but later, it developed into a health partner for women. The application covers all phases of the reproductive cycle, from menstruation to preparations for conception, pregnancy, early motherhood, perimenopause and menopause. [ 1 ]


Flo provides reminders of upcoming menstrual cycles and a place to record various other health symptoms such as contraceptive methods, vaginal discharge, water intake, pains, mood swings, and sexual activity. [ 1 ]


A community section was added in 2017, which allows users to anonymously answer and ask questions on health issues. In 2023, Flo launched Symptom Checker in the United States, a digital tool developed by a multidisciplinary team of doctors, scientists, and engineers. It focuses on helping women by encouraging awareness and understanding of their symptoms and filtering this information to present at appropriate times. It covers several reproductive health conditions, such as polycystic ovary syndrome (PCOS). Flo's Symptom Checker is not a diagnostic tool, it does not provide medical advice, and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. [ 18 ]


Content on the app is reviewed by a board of medical professionals, on behalf of Flo Health. The board advises the developers on medical-related issues, with advisors consisting of medical experts such as professional GB/GYN's and MDs. The purpose of the board is to ensure that Flo Health's content is accurate and based on scientific evidence. [ 19 ]  The app also aims to increase awareness of conditions that can often be confused for period symptoms, such as Heavy Menstrual Bleeding and PCOS. [ 19 ] [ 20 ]


Flo Health has invested in researching taboos and cultural differences for women. In 2019, Flo announced they had completed a survey of 200,000 women globally, as a wider study into  period poverty . The study found a number of common problems, such as 34% of those surveyed believing that period poverty is only an issue in  developing countries . [ 21 ]


Flo collaborated with the  United Nations Population Fund 's (UNFPA) sexual and reproductive health agency in a project to assist women with disabilities. As a UNFPA partner, Flo took part in the Nairobi Summit for  International Conference on Population and Development  (ICPD) and committed to advancing women's reproductive health. [ 22 ] [ non-primary source needed ]  Similar partnerships were agreed with European Board and College of Obstetrics and Gynaecology (EBCOG) to develop educational materials and also contribute to awareness about women's health. [ 23 ]


In February 2019, it was alleged in reports that Flo had been sending users' health data to Facebook [ 24 ]  without users' informed consent, [ 25 ]  and in violation of Facebook's developer policies. [ 26 ]  In response to the allegations of private data misuse, a complaint was filed against Flo Health, Inc by the FTC. [ 27 ]


Flo responded that it never sold any data point to Facebook as well as never used data from Facebook Analytics for advertisements. Flo nevertheless deleted Facebook SDK from app, filed the request to delete all user data from Facebook Analytics and released an app update. [ 26 ] [ 28 ]


The FTC complaint ultimately led to Flo and the FTC reaching a settlement. [ 29 ]  This resolution was reached not as an admission of wrongdoing on Flo's part but as a means to avoid prolonged legal proceedings and associated costs, thereby enabling closure on the matter. The agreement obliged Flo to undertake an independent privacy audit. In March 2022, Flo successfully completed it. Independent auditors did not identify any material gaps or weaknesses in Flo's privacy practices and found that Flo's own practices were consistent with its publicly stated Privacy Policy. [ 26 ] [ 28 ]


Since then, Flo has reinforced its privacy and security measures and underwent further third-party independent audits. It obtained international standards in privacy and security, including security ISO 27001 and Privacy ISO 27701 certifications. Flo was independently tested against various security and privacy controls in the ISO framework. In 2023, Flo Health established a Privacy and Security Advisory Board composed of experts across various fields focused on privacy and security practices, particularly in the femtech industry. [ 27 ] [ 29 ] [ 30 ]


In March 2024, the  Supreme Court of British Columbia  certified a class action against Flo for allegedly sharing intimate data with Facebook and other third parties without user knowledge. [ 31 ]


In September, 2022, as a response to  Roe v. Wade  being  overturned , Flo sped up the release of a feature called “Anonymous Mode”. This mode allows users to access the app without any personal identifiers such as name, email address, and technical identifiers from being associated with their health data. [ 32 ] [ 33 ]


Flo has partnered with  Cloudflare , the same company that Apple worked with for the  iCloud Private Relay , to integrate an Oblivious HTTP system, App Relay Gateway, which ensures that no single party processing user data for Anonymous Mode accounts has complete information on both who the user is and what they are trying to access. [ 34 ] [ 35 ]


The feature has received positive feedback and was praised by Andrew Crawford, Senior Policy Counsel at the center for  Democracy  & Technology. [ 36 ]


In 2023, Flo Health open-sourced the technology behind its Anonymous Mode feature. The company also added post-quantum cryptography, safeguarding sensitive health information from potential security risks posed by quantum computers.


Flo's Anonymous Mode feature was recognized on both  Fast Company's  World Changing Ideas 2023 [ 37 ]  and TIME's Best Inventions List 2023. [ 38 ]


Flo's Anonymous Mode won International Association of Privacy Professionals’ (“IAPP”) Legal Innovation Awards 2022. [ 30 ]


Flo is a  CES 2019  Innovation Awards Honouree in the Software and Mobile Applications category. [ 39 ]


Free bleeding  is the practice of  menstruating  without blocking or collecting the period flow. In recent years it has become a subject of public debate. [ 1 ]


The movement started in the 1970s as a reaction to  toxic shock syndrome , a rare and sometimes fatal condition that can be caused when bacteria grow in  tampons  worn to absorb menstrual bleeding. [ 2 ]  It regained popularity in 2014 as a result of a prank originating on the internet site  4chan . [ 3 ]   Kiran Gandhi  ran in the  London Marathon  while free bleeding as a symbolic act to combat menstrual stigma around the world. [ 4 ] [ 5 ]  The movement focuses on women's and gender minorities' own comfort. [ 6 ]


Free bleeding underwear, a result of the free bleeding movement, has received media attention. [ 7 ]  These products are in response to the use of tampons. [ 8 ]


Functional periodicity  is a term that emerged around the late 19th century around the belief, later to be found invalid, that women suffered from physical and mental impairment during their  menstrual cycle . Men held a higher status and were regarded as superior to women at this period in time. Many prominent male psychologists promoted the idea of functional periodicity. Women were not seen as being fit for certain types of work, responsibilities, and roles because of this idea. [ 1 ]  The idea of functional periodicity stems from ancient taboos and rituals that were passed on from generation to generation. It then developed into an actual theory in the twentieth century. [ 1 ]


Functional periodicity was investigated by a female psychologist named Leta Hollingworth. She made key contributions in the research of functional periodicity, as well as in the feminist movement at the time. Hollingworth, along with her husband Harry Hollingworth, established exceptional research on the idea of functional periodicity and created research studies investigating the science of motor/learning tasks involving the human body. [ 2 ]  Her research impacted how society viewed women, despite the patriarchal opinions held by many.


Functional periodicity was the idea of women being functionally impaired during their menstruation cycle. The untested hypothesis of the time was supported by men, because at this time they dominated society, and this idea helped to keep women in a subordinate position. Women were viewed as not qualified for certain types of work, achievements, and certain responsibilities. The belief also reinforced the stereotype of women being fragile in physical and emotional well-being. [ 2 ]  Multiple studies were performed to look at mental and physical (motor) abilities during menstruation. Many men concluded that women were not fit for certain work and responsibilities. For example, in the eighteenth and nineteenth century, there was debate about whether or not women should participate in higher education. Many argued that women should not go on to pursue higher education because of the dangers that may be involved relating to physiological circumstances. [ 1 ]  An example of reasoning using functional periodicity is a quote by  Henry Maudsley  in 1874. He further states: [ 1 ]


This is a matter of physiology, not a matter of sentiment... not a question of two bodies and minds that are in equal physical condition, but if one body and mind capable of sustained and regular hard labor, and of another body and mind which for one quarter of each month, during the best years of life, is more or less sick and unfit for hard work.


This quote exemplifies the sexist beliefs expressed during this time period. Because of these opinions and beliefs, the idea of functional periodicity became more relevant in American society.


The idea of functional periodicity stems from past cultural superstitions. In the past, menstruation has been thought of as superstitious and taboo. [ 1 ]  An example of this line of thought comes from the British Medical Journal, which discusses the question of whether or not a menstruating woman can contaminate or damage food by touching it. Many individuals believed in this superstition and reinforced it. [ 1 ]


Leta Hollingworth  was born on the Nebraska frontier in 1886. When she was an adolescent, her mother died, which lead to rough household conditions within the family. [ 2 ]  Despite the difficulties, she did exceptionally well in school. This drove her to pursue her education further, which resulted in her graduating from University of Nebraska. While studying there, she met Harry Hollingworth and married him soon after. [ 2 ]  She began teaching while her husband enrolled in a doctoral program at Columbia University, but because she was married she could no longer teach in the state of New York. At the time, this was against the law. [ 2 ]  This barrier fueled Hollingworth's feminist activism. When she finally got the opportunity to enroll in the psychology program at Columbia University under  Edward Thorndike , she took it. At the end of the program, she decided to study functional periodicity for her dissertation research. [ 2 ]


Hollingworth wanted to investigate the idea of functional periodicity and its assumptions about women. [ 2 ]  She started by designing two separate studies. The first study that was designed tested men and women on a series of mental and motor tasks while the second study monitored only females over a 30-day period. Her results showed there was no significant difference in physical and emotional tasks when a woman is menstruating and when she is not. [ 2 ]


Leta Hollingworth was a clinical psychologist and feminist activist who conducted psychological research on several theories involving women. Some of these theories included the  variability hypothesis  and functional periodicity. She was quite instrumental in disproving the theory of functional periodicity, which was widely believed to be true by scientists as well as the general public.


For her dissertation research at Columbia Teacher's College, Hollingworth decided to conduct an investigation on functional periodicity, which she considered to be an unfair assumption about women that lacked any scientific grounds to justify itself. [ 2 ]  Hollingworth completed her dissertation under the supervision of the psychologist Edward Thorndike, a major proponent of the variability hypothesis. Though they held conflicting views, Hollingworth thanked him for aiding her. Hollingworth saw it as her duty as a feminist to prove through scientific study that women were equally as capable and intelligent as men in all of their pursuits, even during menstruation. Her dissertation included three studies dealing with functional periodicity among women, two of which were intensive  and one which was extensive. Her studies on functional periodicity helped to expand the view of menstruation and reduce bias towards women.


Leta Hollingworth decided to use tests that had been used previously by psychologists to complete her study. She decided to use a familiar tapping test and steadiness test to assess motor ability. [ 3 ]  She had a total of eight participants, including six women and two men. The participants ranged from 23–45 years old.


The tapping test was administered by having each participant tap a brass rod that was connected to a brass plate 400 times with their right hand to record maximal speed. Stanley Hall approved of this apparatus and stated how important it was for measuring muscle control. This is important because G.S. Hall is one of the leading male figures who stated, "Women... can make less accurate and energetic movements, and the mental activities are less brilliant."


After the data was analyzed, the researchers noted that there is no data from this study that suggests that women are experiencing more fatigue, less will power, and diminished energy during their menstrual cycle. Fatigue from the tests occurred similarly for men and women. The first 200 taps were faster compared to the last 200 taps.


The steadiness test was measured by having each participant hold a brass rod 2.5 mm in diameter at arm's length. This rod was in a hole 6 mm in diameter. While standing they were asked to hold it for 30 seconds and make the least amount of contact with the hole. Each contact was measured by an electric counter. Due to high variability of the averages the data was deemed unreliable. This was proved by the fact that outside or external forces could affect the outcome greatly. Examples of this would be if the participant coughed, took a breath or got startled by a noise.


Not only did Leta Hollingworth study motor ability, she also sought to study mental ability as well. This was done by using two specific tests, color naming and saying opposites. Color naming was observed by having a card face down laid in front of the participant. [ 2 ]  Each participant was to name the color on the card as quickly as possible. The opposites test used a list of 50 words to test for mental ability as well. The words were presented to the individual in two columns and the words were typed. The participants went through the list as quickly as possible, naming the opposite to each word.


Lastly, she decided to do one more experiment involving 17 females. This study was to observe steadiness, tapping, and the opposites test. In this study, ages ranged from 20 to 40 years old. This extensive experiment was much the same as the intensive experiments involving the 8 participants. They were conducted every 3rd day for 30 days. Two trials were administered at every sitting to help with reliability. The experiment provided results that were very similar to her prior intensive experiment.


Aditi Gupta  ( Hindi :  अदिति गुप्ता ) is an Indian author and co-founder of  Menstrupedia Comic . [ 1 ]  She and her husband, both  National Institute of Design  Alumni, co-founded  Menstrupedia Comic  in 2012. [ 2 ]  In 2014, she was named in the  Forbes  India 30 Under 30  2014 list. [ 3 ]


Aditi Gupta is an engineering graduate and a post-graduate in new media design from the  National Institute of Design ,  Ahmedabad . She was born in  Garhwa  in  Jharkhand ,  India . [ 4 ]  Aditi met her husband, Tuhin Paul in the  National Institute of Design  where they both worked on several projects together. They found a severe lack of awareness about menstruation even among the most educated people, and that many still believed and followed menstrual myths. [ 5 ]  Drawing from her experiences during her teen-age she started Menstrupedia.


She started menstruating at the age of 12, [ 6 ]  however, she was taught about  menstruation  it in school at the age of 15 like other schools in India. She had to also abide by the age-old traditions while menstruating, such as, not allowed to touch a place of worship, and sit on other people’s beds, and wash and dry her clothes separately. [ 6 ]  Even, She was not allowed to use the  sanitary napkins  available in the market as buying them would jeopardise the family’s dignity. [ 7 ]  She bought her first sanitary napkin at the age of 15.


The lack of awareness and education about menstruation motivated her to undergo research on the subject for one year. [ 7 ]   She collated information from doctors and girls which gave her an idea to start a comic book with three young girls and a doctor as the main characters. She put up the comic books on a website (www.talesofchange.in). In November 2012, Gupta and her husband, Paul started Menstrupedia to spread more knowledge and awareness about the subject. [ 8 ]  It originally began as a thesis project while they were in  National Institute of Design ,  Ahmedabad . The website has developed into a platform ‘providing information on puberty and sexuality for pre-teens and teenagers.’


Menstrupedia provides a user-friendly guide to menstruation, hygiene and puberty and helps break myths associated to them. The aim of the website is to present this information in a  culturally sensitive  and an easy-to-understand way through  digital media . The website contains various  comic books ,  blogs , Q&A section and a Learn section. As of 2018, the comics are available in fourteen languages and have been utilised in more than 18 countries. [ 9 ]  Gupta prepared the materials used in schools in five states of North India currently. [ 10 ]  Gupta distributed these comics, in schools in  Mehsana ,  Gandhinagar ,  Ahmedabad  and  Ranchi , where the girls, their parents and teachers liked them a lot. [ 11 ]   Menstrupedia  has started several campaigns in collaboration with Whisper India such as Touch the Pickle movement in collaboration with many actresses like  Shraddha Kapoor ,  Parineeti Chopra ,  Kalki Koechlin ,  Neha Dhupia ,  Mandira Bedi  among others. She was listed on the  Forbes  India U-30 list. [ 3 ]


Menstrupedia  receives one  lakh  visitors every month. [ citation needed ]  Her comic books have been used by NGOs like Protsahan, Munshi Jagannath Bhagwan Smriti Sansthan, Instincts, Kanha along with two Buddhists monasteries in Ladakh.


Humans For Humanity  ( HFH ) is  a  non-governmental organization , founded by renowned  social worker  Anurag Chauhan , headquartered in  Dehradun , India. It is working to bring awareness about  menstrual health , hygiene among women across India. It is providing health, hygiene and comfort to women, especially in poverty-stricken and rural areas in India. The organization empowers women by educating women and young girls on  menstruation  and menstrual hygiene, and by conducting workshops to produce low-cost sanitary pads. [ 1 ] [ 2 ] [ 3 ]  The WASH project started by Humans For Humanity has reached over 3 million women in over 6 states in India in the last 6 years, as of October 2020. [ 4 ] [ 5 ]


It was founded in 2014 by  Anurag Chauhan . For his work with Humans For Humanity, Chauhan honored with the International Women Empowerment Award by the  Ministry of Women and Child Development ,  Ministry of Drinking Water and Sanitation ,  Government of India  and  UNICEF  in 2019. [ 6 ]
During the pandemic the organisation has been providing aid & essentials to over 8000 families in various parts of the country, supporting communities, low income group families, trans men, widows, maids, etc. [ 7 ] [ 8 ]  The NGO has started an employment generation programs to uplift and empower communities, making them financially stable & independent even during the pandemic. [ 9 ]  The WASH project which is a pilot project of the organisation has been working to promote menstrual hygiene among the women of rural areas of six states of the country including Uttarakhand, Delhi, Rajasthan, Haryana and others, decided to work on the initiative for trans men since last year. [ 10 ]


It was founded in 2014 by social activist  Anurag Chauhan . [ 3 ]


The NGO runs a project WASH – Women, Sanitation, Hygiene, which educates rural women about  Menstrual hygiene  and provides training to them for making bio-degradable  Sanitary napkin . It is an initiative to bring awareness among menstruating women. The initiative received support from  Bollywood  actress   Twinkle Khanna . [ 11 ]  The project is being run in many villages, slums, government schools and colleges across India. It organized hundreds of such workshops and reached out to over 3 million women in India. [ 12 ] [ 4 ] [ 3 ] [ 13 ] [ 14 ]


It trains women to make bio-degradable sanitary pads at an affordable cost. The women-centric workshop is headed by experienced doctors to make women aware of the biological reasons behind menstruation, stages from teenage to  menopause , and several hormonal changes. In the community, counseling is provided to women in need who are dealing with menopause. With a separate team of nutritionists, the workshop provides information related to importance of a healthy diet and food. Affordability and quality are the two big concerns in sanitary napkins. Therefore, the organization trains women on how to make good sanitary napkins at their homes. It also covers the adverse effects of poor menstrual hygiene and spreads awareness about the proper disposal of napkins in the waste bin. [ 1 ] [ 3 ]


In May 2016, Humans For Humanity launched an initiative called 'Stree-The Woman'. [ 15 ]  It is a one-day event that focuses on self-growth, self-empowerment and self-love. [ 16 ]
In 2019, the event was organized by the NGO, in association with Sipping Thoughts and  BW Businessworld , which was attended by personalities like  Rita Bahuguna Joshi , Liza Verma, Dr. Varun Katyal,  Ambika Pillai , Malini Ramani and  Sandip Soparrkar . [ 17 ]


In the year 2018, the organization started a new campaign named 'Breaking the Bloody Taboo.' The main aim of this campaign is to stop the old-age taboo against women. In one of the campaigns in  Rajasthan , the team members of Humans For Humanity organized a session with young girls and women of menstruating age. In another session, the founder of Humans for Humanity,  Anurag Chauhan  talked about the importance of holy plant  Tulsi  and handed over a few leaves to women and asked them to nurture the sampling and observe the results after a month. [ 1 ] [ 2 ] [ 12 ]


During the difficult times of nationwide lockdown in India, Human for Humanity came forward to help women and train them to make hygienic sanitary napkins at home safely. [ 18 ]  Under the WASH project by Humans for Humanity, the NGO is actively worked in six different states across India to serve and employ women from villages. The initiative has made hundreds of women financially independent and empowered. [ 19 ] [ 20 ] [ 21 ] [ 22 ]


During the lockdown in 2020, the workshop fed more than 1200 families in and around the slums of  Delhi  for six months. Humans For Humanity set up a transit camp and served people in the  Kathputli Colony  in the Anand Parbat area. Amid the  COVID-19 pandemic  and lockdown, schools have adapted themselves to online teaching. During these times, Humans for Humanity took the initiative to organize an online traditional puppetry program to give children interactive learning. The aim was to innovate the online learning methods and revive the centuries-old traditional art form. As soon as the lockdown was lifted in  Delhi , the NGO started an employment program for street artists. Under the program, the community introduced artists to several schools and helped them generate income through various performances and online events. [ 23 ]


In 2020, Humans For Humanity launched 'Red Cloth Campaign' during the  COVID-19 pandemic , to spread awareness about menstruation and bust the taboos. Actor  Lisa Ray  and singer  Shibani Dandekar ,  Kirti Kulhari ,  Kubra Sait ,  Divya Seth  supported the campaign along with thousands of social media users. [ 24 ]


In April 2022, the WASH project was launched in Telangana by Humans For Humanity and has successfully conducted menstrual hygiene management & health workshops in many villages such as Challur village, Pochampalli village, Ghanmukla village, Reddipalli village, Keshavpatnam and many more. [ 25 ]


In September 2019, Humans for Humanity hosted an event called 'The Conversation Fest', in association with Sipping Thoughts, where  Karan Johar  interviewed  Ma Anand Sheela , former spokesperson of  Rajneesh movement . [ 26 ]


In December 2019, the NGO organized a talk, BW Dialogue in association with  BusinessWorld  and Sipping Thoughts, where  Ma Anand Sheela , candidly recounted her feelings for  Bhagwan Shree Rajneesh . [ 27 ]


The  hypothalamic–pituitary–gonadal axis  ( HPG axis , also known as the  hypothalamic–pituitary–ovarian/testicular axis ) refers to the  hypothalamus ,  pituitary gland , and  gonadal glands  as if these individual  endocrine glands  were a single entity. Because these glands often act in concert,  physiologists  and  endocrinologists  find it convenient and descriptive to speak of them as a single system.


The HPG axis plays a critical part in the development and regulation of a number of the body's systems, such as the reproductive and immune systems. Fluctuations in this axis cause changes in the hormones produced by each gland and have various local and systemic effects on the body.


The axis controls development, reproduction, and aging in animals.  Gonadotropin-releasing hormone  (GnRH) is secreted from the  hypothalamus  by  GnRH-expressing neurons . The anterior portion of the  pituitary gland  produces  luteinizing hormone  (LH) and  follicle-stimulating hormone  (FSH), and the gonads produce  estrogen  and  testosterone .


In  oviparous  organisms (e.g. fish, reptiles, amphibians, birds), the HPG axis is commonly referred to as the hypothalamus-pituitary-gonadal-liver axis (HPGL-axis) in females. Many egg-yolk and chorionic proteins are synthesized heterologously in the liver, which are necessary for ovocyte growth and development. Examples of such necessary liver proteins are  vitellogenin  and choriogenin.


The  HPA , HPG, and  HPT  axes are three pathways in which the hypothalamus and pituitary direct neuroendocrine function.


The  hypothalamus  is located in the brain and secretes GnRH. [ 1 ]  GnRH travels down the anterior portion of the pituitary via the  hypophyseal portal system  and binds to receptors on the secretory cells of the  adenohypophysis . [ 2 ]  In response to GnRH stimulation these cells produce LH and FSH, which travel into the blood stream. [ 3 ]


The pulsatile release of GnRH by hypothalamic neurons is necessary for adequate gonadotropin production by the pituitary. Continuous secretion of GnRH uncouples the gonads from pituitary regulation and leads to decreased synthesis of gonadotropins and hypogonadism. [ 4 ]  The frequency and amplitude of GnRH pulses are tightly regulated, particularly in women, over the course of the reproductive cycle. For instance, the FSHβ gene exhibits ultrasensitive behavior in response to GnRH pulse frequency, with its expression sharply increasing at lower pulse frequencies and decreasing at higher frequencies. This ultrasensitive response is enhanced by the involvement of multiple mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, p38, and ERK5, which form a complex network of feedback and feedforward loops. Different pulse frequencies of GnRH affect the production of gonadotropins, with rapid GnRH pulsatility promoting LH synthesis and slower pulsatility favoring FSH production. [ 5 ]  This ultrasensitive mechanism ensures that small changes in GnRH pulse frequency can lead to significant alterations in gonadotropin synthesis, thereby fine-tuning the reproductive endocrine system.


These two hormones play an important role in communicating to the gonads. In females FSH and LH act primarily to activate the  ovaries  to produce estrogen and inhibin and to regulate the  menstrual cycle  and  ovarian cycle . Estrogen forms a  negative feedback loop  by inhibiting the production of GnRH in the hypothalamus.  Inhibin  acts to inhibit  activin , which is a peripherally produced hormone that positively stimulates GnRH-producing cells.  Follistatin , which is also produced in all body tissue, inhibits activin and gives the rest of the body more control over the axis. Interestingly, follistatin has been shown to also be upregulated by exercise to inhibit the inhibition of muscle growth by myostatin. [ 6 ]  This dual role of exercise in modulating activin inhibition and influencing the HPO axis presents a compelling direction for future exercise physiology research.


Kisspeptin helps to regulate the HPO axis by acting as a mediator. This neuropeptide, encoded by the KISS1 gene, primarily exerts its effects by binding to its receptor, KISS1R (also known as GPR54), on GnRH neurons in the hypothalamus. [ 7 ]  By stimulating GnRH release, kisspeptin indirectly promotes the secretion of LH and FSH from the pituitary gland. Two main populations of kisspeptin neurons have been identified in the hypothalamus: one in the arcuate nucleus (ARC) and another in the anteroventral periventricular nucleus (AVPV) in rodents, or the preoptic area (POA) in humans. [ 7 ]  These neurons are involved in both the negative and positive feedback mechanisms of estrogen on GnRH secretion, with ARC kisspeptin neurons mediating negative feedback and AVPV/POA neurons facilitating the preovulatory LH surge. [ 8 ]  Kisspeptin's influence extends beyond the hypothalamus, as it has been shown to have direct effects on the pituitary and ovaries, regulating processes such as follicle development, oocyte maturation, and ovulation. Dysregulation of the kisspeptin system has been implicated in various reproductive disorders, including polycystic ovary syndrome (PCOS) and infertility, highlighting its importance in maintaining normal reproductive function. [ 9 ]  These kisspeptin neurons act as central processors for relaying signals from the periphery to GnRH neurons and are essential for the onset of puberty and maintenance of normal reproductive function.


In addition,  leptin  and  insulin  have stimulatory effects and  ghrelin  has inhibitory effects on  gonadotropin-releasing hormone  (GnRH) secretion from the  hypothalamus . [ 10 ]   Kisspeptin  also influences GnRH secretion. [ 11 ]


Leptin, an adipocyte-derived hormone, exerts a stimulatory effect on GnRH secretion through multiple mechanisms. While GnRH neurons do not express leptin receptors directly, leptin influences GnRH neuronal activity indirectly via regulation of downstream mediators such as neuropeptide Y, α-melanocyte-stimulating hormone, and agouti-related peptide. [ 12 ]  Furthermore, leptin promotes GnRH function by acting on kisspeptin neurons, which regulate GnRH release as discussed previously. In the hypothalamus, leptin has been shown to accelerate GnRH secretion dose-dependently, specifically affecting pulse frequency rather than amplitude. At the pituitary level, leptin directly stimulates the release of LH and, to a lesser extent, FSH via nitric oxide synthase activation in gonadotropes. [ 12 ]


Insulin, another metabolic hormone, also plays a significant role in modulating GnRH secretion. Central infusion of insulin has been associated with increased LH secretion in diabetic male sheep and female rats, suggesting a neuronal action of insulin in regulating LH release. Insulin receptor signaling in GnRH neurons has been shown to increase GnRH pulsatile secretion and consequent LH secretion, particularly in the context of obesity. This effect appears to be sexually dimorphic, with a more pronounced response observed in female rodents compared to males. [ 13 ]


In contrast to the stimulatory effects of leptin and insulin, ghrelin exerts predominantly inhibitory effects on GnRH secretion. Ghrelin, commonly known as the “hunger hormone,” has been shown to decrease the firing rate and burst frequency of GnRH neurons in a sex- and estrous cycle-dependent manner.This inhibitory effect is mediated through the growth hormone secretagogue receptor (GHS-R) expressed on GnRH neurons. Ghrelin's action on GnRH neurons involves a decrease in the frequency of GABAergic miniature postsynaptic currents and is dependent on retrograde endocannabinoid signaling. At the hypothalamic level, ghrelin has been demonstrated to inhibit GnRH secretion from hypothalamic fragments of ovariectomized female rats. [ 14 ]


The integration of these metabolic signals ensures that reproduction occurs under favorable energetic conditions. Leptin serves as a permissive signal for puberty onset, with a threshold level necessary for normal pubertal progression. Insulin sensitivity in GnRH neurons is important for maintaining normal reproductive function, particularly in the face of metabolic challenges such as obesity. Ghrelin, on the other hand, acts as a signal of energy insufficiency, with persistently elevated levels potentially delaying the normal timing of puberty. Evolutionarily speaking, this makes sense as it is unwise for the body to spend excess energy that it does not have to grow the body larger. Additionally, the effects of these hormones on GnRH secretion can vary depending on the stage of the estrous cycle, nutritional status, and other physiological factors.


From a larger picture, the HPO axis exhibits a concept known as bistability which is responsible for the maintenance of a cyclical pattern in ovarian activity. This bistability is most obvious in the transition between the follicular and luteal phases, and arises from interactions between positive and negative feedback loops involving GnRH, LH, FSH, estrogen, and progesterone. The kisspeptin system creates a switch-like mechanism driving the transition from negative to positive feedback. The distinct hormone profiles characterizing each phase represent two stable states, with sharp transitions between them ensuring proper timing of ovulation and endometrial preparation.


As previously stated, during the follicular phase, estrogen and LH levels rise, and entry into the luteal phase does not occur unless a surge in these hormones occurs up to a certain threshold. Progesterone levels remain low until after the surge, when they rise in the luteal phase. Throughout this cycle, inhibins provide a clear picture of bistability. These dimeric glycoprotein hormones, primarily produced by granulosa cells in the ovary, act as negative feedback regulators of FSH secretion from the anterior pituitary. During the follicular phase, inhibin B is the predominant form, with its levels rising in parallel to the growth of the dominant follicle. This increase in inhibin B, along with rising estrogen levels, contributes to the suppression of FSH secretion, which is critical for the selection of a single dominant follicle. As the cycle progresses to the luteal phase, inhibin A becomes the primary form produced by the corpus luteum. The declining steroid production by the corpus luteum and the dramatic fall of inhibin A towards the end of the luteal phase allow for FSH to rise during the last few days of the menstrual cycle. This elevation in FSH is important for the recruitment of a new cohort of ovarian follicles in the subsequent cycle. [ 15 ]


After menstruation begins, FSH levels decrease due to estrogen's negative feedback and inhibin B produced by the developing follicle. FSH stimulates aromatase activity in granulosa cells, converting androgens to estrogen. As FSH levels drop, the surrounding follicles develop a more androgen-rich environment. Additionally, the granulosa cells of the dominant follicle release peptides that may inhibit the growth of nearby follicles through autocrine and paracrine mechanisms. The development of the dominant follicle occurs in three stages: recruitment, selection, and dominance. Recruitment happens during the first four days of the menstrual cycle when FSH stimulates the recruitment of a group of follicles from the non-growing pool. Between days 5 and 7, one follicle is selected to continue development while the others undergo atresia, a process influenced by anti-Müllerian hormone (AMH). By day 8, the selected follicle dominates by promoting its growth and inhibiting the development of others. [ 15 ]


During the follicular phase, estradiol levels rise with follicle growth and granulosa cell proliferation. FSH receptors, present only on granulosa cells, increase in number due to cell population expansion, not receptor concentration per cell. Rising FSH and estradiol levels induce LH receptor formation on granulosa cells, enabling small progesterone and 17-OHP production, which enhances LH secretion. FSH also activates steroidogenic enzymes like aromatase and 3β-HSD. Meanwhile, LH receptors on theca cells stimulate androstenedione and testosterone production, which granulosa cells convert to estradiol, demonstrating the two-cell, two-gonadotropin hypothesis of estrogen synthesis. Follicular development then progresses through stages: primordial follicles enlarge into preantral follicles surrounded by granulosa and theca cells, acquiring FSH receptors. These develop into antral follicles and eventually preovulatory follicles. Early follicles produce more androgens due to 5α-reductase activity, but dominant follicles, with high aromatase levels, shift to an estrogen-rich environment, crucial for their selection. [ 15 ]


The LH surge, as previewed earlier, is triggered by rising estradiol levels and occurs about 34-36 hours before ovulation. LH induces granulosa cell luteinization, progesterone synthesis, meiosis resumption, and oocyte release. Proteolytic enzymes and prostaglandins, activated by LH and progesterone, break down the follicular wall, releasing the oocyte. Ovulation typically occurs randomly between ovaries, with some studies suggesting higher fertility potential in right-sided ovulation. [ 15 ]


Post-ovulation, the corpus luteum forms and secretes progesterone and estradiol episodically, regulated by LH. The corpus luteum's lifespan is influenced by LH pulse frequency and amplitude, gonadotropin levels, and luteotropic factors like prolactin, oxytocin, and prostaglandins. Luteolysis involves factors such as endothelin-1 and TNFα, which inhibit steroidogenesis and induce apoptosis. Estrogen and matrix metalloproteinases also contribute to luteal regression. [ 15 ]


Disruptions in the bistable nature of the HPO axis have been implicated in various reproductive disorders. For instance, in polycystic ovary syndrome (PCOS), alterations in the GnRH pulse generator and abnormal androgen feedback may lead to a persistent high-LH state. The GnRH pulse generator in PCOS then becomes less sensitive to the normal inhibitory effects of estrogen and progesterone leading to hyperandrogenism. The hyperandrogenism creates a self-perpetuating cycle, in which the increased GnRH pulse frequency promotes LH secretion over FSH, resulting in a high LH/FSH ratio. Elevated LH stimulates theca cells in the ovaries to produce excess androgens. These elevated androgens further impair the sensitivity of the GnRH pulse generator to negative feedback from estrogen and progesterone. [ 16 ]


Conversely, hypothalamic amenorrhea is characterized by a failure to transition from the low-gonadotropin state to the active reproductive state, due to metabolic or stress-related factors such as overtraining commonly seen in elite athletes. In such a state, menses does not occur at all, rather than partially occur. Even upon return to normal diet or physical activity, the body may take months to years for menses to return to normal, almost as if the body hysterically remembers the previous state of energy deficiency. By preventing menses, the body initiates infertility so that a pregnancy does not occur and cause another source of energy demand. [ 17 ]


Understanding the bistable nature of the HPO axis has significant implications for developing novel therapeutic approaches to restore normal reproductive function. For example, pulsatile GnRH administration has shown promise in restoring normal reproductive function in certain cases of hypothalamic amenorrhea by nudging the system back into its active state. Similarly, novel kisspeptin analogs are being developed to modulate the HPO axis more precisely, potentially offering new treatments for infertility and hormone-dependent cancers. [ 17 ]


One of the most important functions of the HPG axis is to regulate reproduction by controlling the uterine and ovarian cycles. [ 18 ]  In females, the  positive feedback  loop between estrogen and luteinizing hormone help to prepare the follicle in the ovary and the uterus for ovulation and implantation. When the egg is released, the empty follicle sac begins to produce progesterone to inhibit the hypothalamus and the anterior pituitary thus stopping the estrogen-LH positive feedback loop.


During the follicular phase, rising estrogen levels from developing follicles exert positive feedback on the hypothalamus and pituitary, leading to the LH surge that triggers ovulation. After ovulation, the corpus luteum produces progesterone, which inhibits GnRH secretion from the hypothalamus and gonadotropin release from the anterior pituitary, thus terminating the estrogen-LH positive feedback loop.


If conception occurs, the placenta will take over the secretion of progesterone; therefore the mother cannot ovulate again. If conception does not occur, decreasing excretion of progesterone will allow the hypothalamus to restart secretion of GnRH. These hormone levels also control the uterine (menstrual) cycle causing the proliferation phase in preparation for ovulation, the secretory phase after ovulation, and menstruation when conception does not occur. The activation of the HPG axis in both males and females during puberty also causes individuals to acquire secondary sex characteristics. This process, known as gonadarche, is preceded by adrenarche, the maturation of the adrenal glands, which contributes to the production of androgens responsible for some pubertal changes. [ 19 ]


In males, the production of GnRH, LH, and FSH are similar, but the effects of these hormones are different. [ 20 ]  FSH stimulates  sustentacular cells  to release  androgen-binding protein , which promotes  testosterone  binding. LH binds to the interstitial cells, causing them to secrete testosterone. Testosterone is required for normal spermatogenesis and inhibits the hypothalamus. Inhibin is produced by the spermatogenic cells, which, also through inactivating activin, inhibits the hypothalamus. After puberty these hormones levels remain relatively constant. [ citation needed ]


The activation and deactivation of the HPG axis also helps to regulate life cycles. [ 18 ]  At birth FSH and LH levels are elevated, and females also have a lifetime supply of primary oocytes. These levels decrease and remain low through childhood. During  puberty  the HPG axis is activated by the secretions of estrogen from the ovaries or testosterone from the  testes . This activation of  estrogen  and testosterone causes physiological and psychological changes. Once activated, the HPG axis continues to function in men for the rest of their life but becomes deregulated in women, leading to  menopause . This deregulation is caused mainly by the lack of oocytes that normally produce estrogen to create the positive feedback loop. Over several years, the activity the HPG axis decreases and women are no longer fertile. [ 21 ]  Beyond infertility, the diminished level of estrogen causes other effects such as increased bone resorption, unfavorable lipid profiles, hair loss, and skin dryness.


Although males remain fertile until death, the activity of the HPG axis decreases. As males age, the  testes  begin to produce less testosterone, leading to a condition known as post-pubertal  hypogonadism . [ 20 ]  The cause of the decreased testosterone is unclear and a current topic of research. Post-pubertal hypogonadism results in progressive muscle mass decrease, increase in visceral fat mass, loss of libido, impotence, decreased attention, increased risk of fractures, and abnormal sperm production. [ citation needed ]


Sex steroids  also affect behavior, because sex steroids affect the brains structure and functioning. During development, hormones help determine how neurons  synapse  and  migrate  to result in  sexual dimorphisms . [ 22 ]  These physical differences lead to differences in behavior. While GnRH has not been shown to have any direct influence on regulating brain structure and function, gonadotropins, sex steroids, and activin have been shown to have such effects. It is thought that FSH may have an important role in brain development and differentiation.


Testosterone levels have been shown to relate to  prosocial behavior . [ 23 ]  This helps create synaptogenesis by promoting neurite development and migration. Activin promotes neural plasticity throughout the lifespan and regulates the neurotransmitters of peripheral neurons. Environment can also affect hormones and behavior interaction. [ 24 ]


Disorders of the hypothalamic–pituitary–gonadal axis are classified by the World Health Organization (WHO) as: [ 25 ]


Genetic mutations and chromosomal abnormalities are two sources of HPG axis alteration. [ 27 ]  Single mutations usually lead to changes in binding ability of the hormone and receptor leading to inactivation or over activation. These mutations can occur in the genes coding for GnRH, LH, and FSH or their receptors. Depending on which hormone and receptor are unable to bind different effects occur but all alter the HPG axis. [ citation needed ]


For example, the male mutation of the GnRH coding gene could result in hypogonadotrophic hypogonadism. A mutation that cause a gain of function for LH receptor can result in a condition known as testotoxicosis, which cause puberty to occur between ages 2–3 years. Loss of function of LH receptors can cause male pseudohermaphroditism. In females mutations would have analogous effects. Hormone replacement can be used to initiate puberty and continue if the gene mutation occurs in the gene coding for the hormone. Chromosomal mutations tend to affect the androgen production rather than the HPG axis. [ citation needed ]


The HPG axis can be suppressed by  hormonal birth control  administration. Although often described as preventing pregnancy by mimicking the pregnancy state, hormonal birth control is effective because it works on the HPG axis to mimic the luteal phase of a woman's cycle. The primary active ingredients are synthetic  progestins , which mimic biologically derived progesterone. The synthetic progestin prevents the hypothalamus from releasing GnRH and the pituitary from releasing LH and FSH; therefore it prevents the ovarian cycle from entering the menstrual phase and prevents follicle development and ovulation. Also as a result, many of the side effects are similar to the symptoms of pregnancy. Alzheimer's has been shown to have a hormonal component, which could possibly be used as a method to prevent the disease. [ 28 ]   Male contraceptives  utilizing sex hormones approach the problem in a similar way.


The HPG axis can also be suppressed by  GnRH antagonists  or continuous administration of  GnRH agonist , such as in the following applications


Ovulation induction  is usually initially performed by giving an  antiestrogen  such as  clomifene citrate  or  letrozole  in order to decrease negative feedback on the pituitary gland, resulting in an increase in FSH with the aim of increasing  folliculogenesis . It is the main initial medical treatment for  anovulation .


Environment can have large impact on the HPG axis. For example, women with eating disorders tend to have oligomenorrhea (prolonged menstrual cycles greater than 35 days) and secondary amenorrhea (absence of menstruation for at least three consecutive months). Starvation from anorexia nervosa or bulimia causes the HPG axis to deactivate causing women's ovarian and uterine cycles to stop. Stress, physical exercise, and weight loss have been correlated with oligomenorrhea and secondary amenorrhea. [ 29 ]  Similarly environmental factors can also affect men such as stress causing  impotence . Prenatal exposure to alcohol can affect the hormones regulating fetal development resulting in foetal alcohol spectrum disorder. [ 30 ]


These menstrual irregularities are primarily caused by the deactivation of the HPG axis due to chronic energy deficiency and malnutrition associated with these disorders:


In anorexia nervosa, severe caloric restriction and subsequent weight loss lead to a suppression of the HPG axis. This suppression results in changes to the pulsatile release of GnRH from the hypothalamus, reverting the LH secretion pattern to pre-pubertal levels. The altered GnRH pulsatility leads to a decrease in the frequency and amplitude of LH and FSH release from the pituitary gland. Without adequate stimulation from these gonadotropins, ovarian follicles fail to develop properly, leading to insufficient estrogen production and anovulation. [ 31 ]  The starvation state in anorexia nervosa also affects other hormones important ore productive regulation. Leptin, an adipocyte-derived hormone discussed under the Regulation section of this Wikipedia page, is significantly reduced in patients with anorexia nervosa due to the loss of body fat. Low leptin levels contribute to the disruption of normal GnRH secretion, as leptin is needed  for proper hypothalamic function and the initiation of puberty. [ 32 ]


In bulimia nervosa, while patients may not always present with significant weight loss, the cycle of binge eating and purging can still lead to metabolic disturbances that affect the HPG axis. The irregular eating patterns and potential nutritional deficiencies can cause hormonal imbalances, particularly in insulin and testosterone levels, which may contribute to menstrual irregularities. Furthermore, the psychological stress associated with bulimia nervosa can activate the HPA axis, leading to elevated cortisol levels that can interfere with normal reproductive function. [ 32 ]


The HPG axis is highly conserved in the animal kingdom. [ 33 ]  While reproductive patterns may vary, the physical components and control mechanisms remain the same. The same hormones are used with some minor evolutionary modifications. Much of the research is done on animal models, because they mimic so well the control mechanism of humans. It is important to remember humans are the only species to hide their fertile period, but this effect is a difference in the effect of the hormones rather than a difference in the HPG axis.


Khushi  (meaning "Happiness" in  Odia ) is a female health and hygiene program run by the  Government of Odisha  to provide free  sanitary pads  to girl students in Odisha. [ 1 ]  It was launched on February 26, 2018, by the Chief Minister of Odisha  Naveen Patnaik . The Government of Odisha will spend 70 Crore Indian rupees annually for running this program in the state. [ 2 ]


Under this scheme, the Health Department of Odisha Government aims to provide free sanitary pads to 1.7 million girl students from grade 6th to 12th in government and government-aided schools. [ 3 ]  Also, it aims to promote health and hygiene among school going girls and higher retention of girls in school. [ 4 ]


Menstrual leave  is a type of  leave  where a person may have the option to take paid or unpaid leave from their employment if they are  menstruating  and are unable to go to work because of this. [ 1 ] [ 2 ]  Throughout its history, menstrual leave has been associated with controversy and discrimination against men, with very few countries enacting policies. In these countries, menstrual leave is still associated with low uptake. [ 1 ]  It is seen by some as a criticism of women's work efficiency or as  sexism [ 3 ] [ 4 ] [ 5 ]  against men. Supporters of menstrual leave policies compare its function to that of  maternity leave  and view it as a promoter of gender equality. [ 6 ]


Some women experience a condition called  dysmenorrhea  that causes pain during  menstruation . [ 7 ]  Up to 90% of women do not experience problems sufficient to disrupt daily functioning as a result of menstruation, although they may report having some issues prior to menstruation.  Symptoms interfere with normal life, qualifying as  premenstrual syndrome , in 20–30% of women. In 3–8%, symptoms are severe. [ 8 ]   Premenstrual dysphoric disorder  (PMDD) is a severe and disabling form of  premenstrual syndrome  affecting 1.8–5.8% of menstruating women. [ 9 ]


A menstrual leave policy was first applied in some job sectors in post-Revolutionary Russia at the turn of the 20th century. However, because of the resulting discrimination against female workers, the policy was removed in 1927. [ 1 ]


A girls' school in the south  Indian  state of  Kerala  had granted its students menstrual leave as early as 1912. [ 10 ]


In the 1920s, Japanese labor unions started to demand leave (seiri kyuka) for their female workers. In 1947, a  law  was brought into force by the Japanese Labor Standards that allowed menstruating women to take days off work.  Debate  continues as to whether it is a  medical necessity  or a discriminatory measure. [ 11 ] [ 12 ] [ 13 ]


There is a stigma related to menstrual leave. According to Levitt and Barnack-Tavlaris (2020), it may perpetuate stereotypes and further the medicalization of menstruation. [ 2 ]  Taking leave may require telling managers who are males about something the woman believes to be a personal issue. It may portray women as less able than men and could, therefore, lead to further discrimination against women. One suggestion to remove the stigma is to provide additional medical leave for people of all genders. [ 14 ]


In Indonesia, under the Labor Act No. 13 in 2003, women have a right to two days of menstrual leave per month, though these are not additional leaves. [ 15 ]


In Japan, since 1947, Article 68 of the Labour Standards Law states "When a woman for whom work during menstrual periods would be specially difficult has requested leave, the employer shall not employ such woman on days of the menstrual period." [ 16 ] [ 17 ]  While Japanese law requires that a woman going through especially difficult menstruation be allowed to take leave, it does not require companies to provide paid leave or extra pay for women who choose to work during menstruation.


In South Korea, female employees are entitled to menstrual leave according to Article 71 of the Labour Standards Law, [ 18 ]  and are ensured additional pay if they do not take the menstrual leave that they are entitled to. [ 19 ]


In Taiwan, the Act of Gender Equality in Employment [ 20 ]  gives women three days of "menstrual leave" per year, which will not be calculated toward the 30 days of "common sick leave", giving women up to 33 days of "health-related leaves" per year. The extra three days do not come with half-pays once a woman employee exceeds the regulated 30. [ 21 ]


In Europe, as of 2023, there was one country, Spain, with national menstrual leave. [ 1 ] [ 22 ]  Since February 2023, Spain has provided three to five days per month of paid menstrual leave. [ 22 ]


A proposal by the  Italian Parliament  to introduce a menstrual leave policy in 2017 sparked debate in Europe on how menstrual health impacts women in the workforce. The bill would have introduced a policy for companies to offer three days paid leave to women who suffer severe menstrual cramps; the policy was not enacted. [ 1 ]


In Zambia, as of 2015, women are legally entitled to a day off each month due to their menstrual leave policy, known as "Mother's Day". [ 23 ]  If a woman employee is denied this entitlement, she can rightfully prosecute her employer.


Coexist, a  Bristol  community interest firm, introduced a "period policy" in order to give women more flexibility and a healthier work environment. Hoping to break down the menstruation taboo, Coexist became the first company in the United Kingdom to implement this policy. [ 24 ]


Nike  has been widely reported as supporting menstrual leave wherever it operates, but this policy was misrepresented by the media; Nike follows the local labor laws where it operates. [ 1 ]


The  menstrual cycle  is on average 28 days in length. It begins with  menses  (day 1–7) during the  follicular phase  (day 1–14), followed by  ovulation  (day 14) and ending with the  luteal phase  (day 14–28). [ 1 ]  while historically, medical experts believed the luteal phase to be relatively fixed at approximately 14 days (i.e. days 14–28), [ 1 ]  recent research suggests that there can be wide variability in luteal phase lengths not just from person to person, but from cycle to cycle within one person. [ 2 ]  The luteal phase is characterized by changes to hormone levels, such as an increase in  progesterone  and  estrogen  levels, decrease in  gonadotropins  such as  follicle-stimulating hormone  (FSH) and  luteinizing hormone  (LH), changes to the  endometrial lining  to promote  implantation  of the fertilized egg, and development of the  corpus luteum . In the absence of fertilization by sperm, the corpus luteum degenerates leading to a decrease in progesterone and estrogen, an increase in FSH and LH, and shedding of the endometrial lining (menses) to begin the menstrual cycle again. [ 1 ]


After  ovulation  and release of the  oocyte , the  anterior pituitary hormones – follicle-stimulating hormone  (FSH) and  luteinizing hormone  (LH) are released and cause the remaining parts of the dominant  follicle  to transform into the  corpus luteum . It continues to grow during the luteal phase after ovulation and produces significant amounts of hormones, particularly progesterone, and, to a lesser extent,  estrogen  and  inhibin . Progesterone plays a vital role in making the  endometrium   receptive  to  implantation  of the  embryo  and supportive of early pregnancy. High levels of progesterone inhibit the follicular growth. The increase in estrogen and progesterone also lead to increased basal body temperature during the luteal phase. [ 3 ]


The  LH surge  that occurs during ovulation triggers the release of the oocyte and its cumulus oophorus from the ovary and into the fallopian tube and triggers the oocyte to divide and enter metaphase of meiosis II (46 or 2n chromosome) and extrude its first polar body. The oocyte will only continue through meiosis and extrude its second polar body once it is fertilized. Ovulation occurs ~35 hours after the beginning of the LH surge or ~10 hours following the LH surge. Several days after  ovulation , the increasing amount of estrogen produced by the corpus luteum may cause one or two days of fertile  cervical mucus , lower basal body temperatures, or both. This is known as a "secondary estrogen surge". [ 4 ]


The hormones released by the corpus luteum suppress production of the FSH and LH from the anterior pituitary gland. The corpus luteum relies on LH activation on its receptors in order to survive. The loss of the corpus luteum can be prevented by implantation of an  embryo : after implantation, human embryos produce  human chorionic gonadotropin  (hCG), [ 5 ]  which is structurally similar to LH and can preserve the corpus luteum. If implantation occurs, the corpus luteum will continue to produce progesterone for eight to twelve weeks, after which the  placenta  takes over this function. [ 6 ]  In the absence of fertilization, hCG is not produced and the corpus luteum will atrophy in 10–12 days (Luteolysis or luteal regression). The death of the corpus luteum results in falling levels of progesterone and estrogen. The drop in ovarian hormones releases negative feedback on LH and FSH, thereby increasing LH and FSH concentrations and leading to shedding of the endometrium and another round of ovarian follicle selection. [ 7 ]


During the follicular phase in the menstrual cycle, the uterine endometrium is in the proliferative phase which is characterized by an increase in circulating estrogen produced by the developing follicle. Increased estradiol alters the endometrial lining and promotes proliferation of epithelial cells, thickening of the tissue, and elongation of the spiral arteries that provide nutrients to the growing tissue. Estrogen also makes the endometrium more sensitive to progesterone in preparation for the luteal phase. [ citation needed ]


After ovulation and during the luteal phase, the uterine endometrium is in the secretory phase which is characterized by the production of progesterone from the growing corpus luteum. Progesterone inhibits endometrial proliferation, and preserves uterine tissue in preparation for fertilized egg implantation. At the end of the luteal phase, progesterone levels fall and the corpus luteum atrophies. The drop in progesterone leads to endometrial ischemia which will subsequently shed in the beginning of the next cycle at the start of menses. [ 1 ]  This last stage in the luteal or secretory phase may be called the  ischemic phase  and lasts just for one or two days. [ 8 ]


Changes in the level of progesterone during this phase may cause typical symptoms of  pre-menstrual syndrome  (PMS), such as:


Luteolysis [ 1 ]  (also known as  luteal regression ) is the structural and functional degradation of the  corpus luteum , which occurs at the end of the  luteal phase  of both the  estrous  and  menstrual cycles  in the absence of  pregnancy .


Prostaglandin F2 alpha  (PGF2α) has been identified as the key luteolytic hormone in many species. [ 2 ]  PGF2α is released from uterine endometrial cells in a pulsatile pattern when stimulated by oxytocin [ 3 ]  to stimulate both luteolytic activity and further release of oxytocin from the corpus luteum. [ 4 ]


In domestic animals, luteolysis is initiated by the hormones  prostaglandin F2alpha  and  oxytocin  and is dependent on the presence of the uterus. In sheep, communication between the pars nervosa (posterior lobe of the pituitary gland), corpus luteum, and the uterus  endometrium  via the circulatory system is required for luteolysis. Studies with sheep have found that, if the uterine horn is ipsilateral to the ovary possessing the CL is surgically removed, the lifespan of the corpus luteum will increase drastically. [ citation needed ]


Removal of the uterus in primates (including humans) does not prolong the life of the corpus luteum, indicating that a different stimulatory mechanism and source of PGF2α is responsible for luteolysis in these species.  [ 5 ]  It has been proposed that PGF2α is made locally within the ovary and the corpus luteum may be the source of luteolytic PGF2α. [ 6 ]  Asthmatics should take great care when handling this hormone as PGF2α is bronchoconstrictor. [ citation needed ]


During a pregnancy, the corpus luteum remains on the ovary releasing  progesterone  which will maintain a state of uterine quiescence and close the  cervix  until the delivery of the fetus. Alternatively if no implantation of a  blastocyst  occurs, the corpus luteum is degraded to a  corpus albicans  (scar tissue) by PGF2α released by uterine endometrial cells. [ citation needed ]


Degradation of the corpus luteum will result in reduced levels of progesterone, promoting an increase in  follicle-stimulating hormone  (FSH) secretion by the adenohypophysis, which will trigger the development of a new  follicle  on the  ovary . [ citation needed ]


In humans, the placental hormone  human chorionic gonadotropin  continues to maintain the corpus luteum. This is the hormone tested for by the pregnancy test.


If pregnancy occurs in  equine , the placental hormone  equine chorionic gonadotropin  released by  endometrial cup  acts like LH and FSH and stimulates additional ovulations, although the oocytes released during these ovulations are not fertilized. The resulting accessory corpora lutea produce progesterone and keep levels of progesterone high during pregnancy.


Freweini Mebrahtu  ( Ge'ez :  ፍሬወይኒ መብራህቱ ,  romanized:  Frēweyinī Mebrahtu ) is an Ethiopian  chemical engineer  and inventor who won the 2019  CNN Hero  of the year award for her activism in improving girls' access to education. [ 1 ]


Freweini was born in  Ethiopia  and educated in the  United States , studying  chemical engineering  at  Prairie View A&M University . In 2005, she patented a reusable menstrual pad that can be used for up to 2 years with proper care. As of 2019, she employs hundreds of locals in  Tigray region  of  Ethiopia , and makes more than 700,000 of the reusable pads that are mainly provided to non-governmental organizations. [ 1 ]


Her  menstrual product  plus her educational campaign has helped in removing the stigma surrounding menstruation and stopped girls from dropping out of schools due to the stigma. [ 2 ]  The non profit organization Dignity Period has distributed more than 150,000 free menstrual supplies purchased from Freweni's factory. It was reported that attendance among girls improved by 24% due to this effort. [ 2 ]


Menarche  ( / m ə ˈ n ɑːr k i /   mə- NAR -kee ; from  Ancient Greek     μήν  (mēn)  'month' and    ἀρχή  (arkhē)  'beginning') is the first  menstrual cycle , or first  menstrual bleeding , in female  humans . From both social and medical perspectives, it is often considered the central event of female  puberty , as it signals the possibility of  fertility.  Girls experience menarche at different ages. [ 1 ] [ 2 ]  Having menarche occur between the ages of 9–14 in the West is considered normal. [ 3 ]


The timing of menarche is influenced by female  biology , as well as  genetic ,  environmental factors , and  nutritional  factors. [ 4 ]  The mean age of menarche has declined over the last century, but the magnitude of the decline and the factors responsible remain subjects of contention. The worldwide average age of menarche is very difficult to estimate accurately, and it varies significantly by geographical region, race, ethnicity and other characteristics, and occurs mostly during a span of ages from 8 to 16, with a small percentage of girls having menarche by age 10, and the vast majority having it by the time they were 14. [ 3 ]
There is a later age of onset in  Asian  populations compared to the West, but it too is changing with time. For example a Korean study in 2011 showed an overall average age of 12.7, with around 20% before age 12, and more than 90% by age 14. [ 5 ]  A Chinese study from 2014 published in  Acta Paediatrica  showed similar results (overall average of age 12.8 in 2005 down to age 12.3 in 2014) and a similar trend in time, but also similar findings about ethnic, cultural, and environmental effects. [ 6 ]  The average age of menarche was about 12.7 years in  Canada  in 2001, [ 7 ]  and 12.9 in the  United Kingdom . [ 8 ]  A study of girls in  Istanbul , Turkey, in 2011 found the  median age at menarche to be 12.7 years. [ better source needed ] [ 9 ]  In the United States, an analysis of 10,590 women aged 15–44 taken from the 2013–2017 round of the CDC's National Survey of Family Growth
found a median age of 11.9 years (down from 12.1 in 1995), with a mean of 12.5 years (down from 12.6). [ 10 ]


Menarche is the culmination of a series of  physiological  and anatomic processes of  puberty :


No specific hormonal signal for menarche is known; menarche as a discrete event is thought to be the relatively chance result of the gradual thickening of the endometrium induced by rising but fluctuating pubertal estrogen. [ citation needed ]


The  menstruum , or  flow , consists of a combination of fresh and clotted blood with endometrial tissue. The initial flow of menarche is usually brighter than mature menstrual flow. It is often scanty in amount and may be very brief, even a single instance of "spotting". Like other  menses , menarche may be accompanied by  abdominal cramping . [ citation needed ]


In most girls, menarche does not mean that  ovulation  has occurred. In post-menarchal girls, about 80% of the cycles were  anovulatory  in the first year after menarche, 50% in the third and 10% in the sixth year. [ 13 ]  Regular ovulation is usually indicated by predictable and consistent intervals between menses, and predictable and consistent patterns of flow (e.g., heaviness or cramping). Continuing ovulation typically requires a  body fat percentage  of at least 22%. [ 11 ]  An  anthropological  term for this state of potential fertility is nubility. [ citation needed ]


On the other hand, not every girl follows the typical pattern, and some girls ovulate before the first  menstruation . Although unlikely, it is possible for a girl who has engaged in  sexual intercourse  shortly before her menarche to  conceive  and become  pregnant , which would delay her menarche until after the end of the pregnancy. This goes against the widely held assumption that a woman cannot become pregnant until after menarche. A young age at menarche is not correlated with a young age at first sexual intercourse. [ 14 ]


When menarche occurs, it confirms that the girl has had a gradual  estrogen -induced growth of the  uterus , especially the  endometrium , and that the "outflow tract" from the uterus, through the  cervix  to the  vagina , is open.


When a woman experiences menarche, the blood flow can vary from a slow and spotty discharge to a consistent blood flow for 3–7 days. While the color of the blood does range from a brown to bright red color, this is normal; some women have light periods while others have heavy ones; no two women will have an identical experience. [ 15 ]


In very rare instances, menarche may occur at an unusually early age, preceding  thelarche  and other signs of puberty. This is termed  isolated premature menarche , but other causes of  vaginal bleeding  must be investigated and excluded. Growth is usually normal. [ 16 ]  Isolated premature menarche is rarely the first manifestation of  precocious puberty . [ citation needed ]


When menarche has failed to occur for more than three years after thelarche, or beyond 16 years of age, the delay is referred to as  primary amenorrhea .


Certain systemic or chronic illness can delay menarche, such as undiagnosed and untreated  celiac disease  (which often occurs without gastrointestinal symptoms),  asthma ,  diabetes mellitus type 1 ,  cystic fibrosis  and  inflammatory diseases , among others. [ 17 ] [ 18 ] [ 19 ] [ 20 ]  In some cases, because  biochemical tests  are not always discriminatory, underlying pathologies are not identified and the girl is classified as  constitutional growth delay . [ 21 ]  Short stature, delayed growth in height and weight, and/or delayed menarche may be the only clinical manifestations of  celiac disease , in absence of any other symptoms. [ 19 ] [ 22 ] [ 23 ] [ 24 ]  According to a review article, there may also be an association between early age at menarche and  breast cancer  risk. [ 25 ]


Studies have been conducted to observe the association of the timing of menarche with various conditions and diseases. Some studies have shown that there may be an association between early or late-age menarche and  cardiovascular disease , although the mechanism of the association is not well understood. [ 26 ]  A systematic review has concluded that early age at menarche is also a risk factor for the  insulin resistance  condition. [ 27 ]  There is conflicting evidence regarding the association between  obesity  and timing of menarche; a meta-analysis and systematic review has determined that more studies must be conducted to make any definitive conclusions about this association. [ 28 ]


Some of the aspects of family structure and function reported to be independently associated with earlier menarche [antenatal and early childhood]


Other research has focused on the effect of childhood  stress  on timing of puberty, especially female. Stress is a vague term and studies have examined conditions ranging from family tensions or conflict to wartime refugee status with threat to physical survival. The more dire social conditions have been found to be associated with delay of maturation, an effect that may be compounded by dietary inadequacy. There is more uncertainty and mixed evidence as to whether milder degrees of stress or early-life under-nutrition can accelerate puberty in girls as would be predicted by  life history theory  and demonstrated in many other mammals. [ 31 ]


The understanding of these environmental effects is incomplete and the following observations and cautions are relevant:


There were few systematic studies of timing of menarche before the later half of the 20th century. Most older estimates of average timing of menarche were based on observation of a small homogeneous population not necessarily representative of the larger population, or based on recall by adult women, which is also susceptible to various forms of error. Most sources agree that the average age of menarche in girls in modern societies has declined, though the reasons and the degree remain subjects of controversy. From the sixth to the fifteenth centuries in Europe, most women reached menarche on average at about 14, between the ages of 12 and 15. [ 34 ]  The average age of menarche dropped from 14-15 years in the nineteenth century to 12-13 years in the present, but it seems that girls in the nineteenth century had a later age at menarche compared to girls in earlier centuries. [ 35 ]  A large North American survey reported only a 2–3 month decline from the mid-1970s to the mid-1990s. [ 36 ]  A 2011 study found that each 1 kg/m 2  increase in childhood  body-mass index  (BMI) can be expected to result in a 6.5% higher absolute risk of early menarche (before age 12 years). [ 37 ]


This is called the secular trend. [ 38 ] [ 39 ]


Fewer than 10% of U.S. girls start to menstruate before 11 years of age, and 90% of all U.S. girls are menstruating by 13.8 years of age, with a median age of 12.4 years. This age at menarche is not much different (0.3 years earlier) than that reported for U.S. girls in 1973. Age at menarche for non-Hispanic black girls was significantly earlier than that of white girls at 10%, 25%, and 50% of those who had attained menarche, whereas non-white Mexican American girls were only slightly earlier than the white girls at 25%. [ 40 ]


Menstruation is a cultural as well as scientific phenomenon as many societies have specific rituals and cultural norms associated with it. These rituals typically begin at menarche and some are enacted during each menstruation cycle. The rituals are important in determining a status change for girls. Upon menarche and completion of the ritual, they have become a woman as defined by their culture.


For young women in many cultures, the first menstruation is a marker that signifies a change in status. Post-menarche, the young woman enters a stage called maidenhood, the stage between menarche and marriage. [ 41 ]  There are cultures that have in past centuries, and in present, practiced rites of passage for a girl experiencing menarche. [ 42 ]  Canadian psychological researcher Niva Piran claims that menarche or the perceived average age of puberty is used in many cultures to separate girls from activity with boys, and to begin transition into womanhood. [ 43 ]


In some cultures, a party, or celebration is thrown to show the girl's transition to womanhood. This party is similar to the  quinceañera  in Latin America, except that a specific age marks the transition rather than menarche. In  Morocco , the girl is thrown a celebration. All of her family members are invited and the girl is showered with money and gifts.


When a  Japanese girl  had her first period, the family sometimes celebrated by eating red-colored rice and beans  ( sekihan ) . The color of blood and the red of  sekihan  are not related. All the rice of ancient times of Japan was red. Since rice was precious in ancient Japan (usually,  millet  was eaten), it was eaten only during the celebration.  Sekihan  was the tradition of an ancient custom. The celebration was kept a secret from extended family until the rice was served. [ 44 ]


In some  Indian  communities, young women are given a special menarche ceremony called  Ruthu Sadangu . [ 45 ]


The  Mescalero  Apaches place high importance on their menarche ceremony and it is regarded as the most important ritual in their tribe. Each year, there is an eight-day event celebrating all of the girls who have menstruated in the past year. The days are split between feasting and private ceremonies reflecting on their new womanly status. [ 46 ]


In  Australia , the  Aboriginals [ which? ]  treat a girl to "love magic". She is taught the ways of womanhood by the other women in her tribe. Her mother builds her a  menstruation hut  to which she confines herself for the remainder of her menses. The hut is burned and she is bathed in the river at the end of menstruation. When she returns to the village [ clarification needed ] , she is paired with a man who will be her husband. [ 44 ]


In the  United States , some public schools have a  sex education  program that teaches girls about menstruation and what to expect at the onset of menarche (often this takes place during the fourth grade). Historically menstruation has been a social taboo and girls were taught about menarche and menstruation by their mothers or a female role model. Then, and to an extent now, menstruation was a private matter and a girl's menarche was not a community phenomenon. [ 47 ]


The  Ulithi  tribe of  Micronesia  call a girl's menarche  kufar . She goes to a  menstrual house , where the women bathe her and recite spells. She will have to return to the menstruation hut every time she menstruates. Her parents build her a private hut that she will live in until she is married. [ 44 ]


In  Sri Lanka , an  astrologer  is contacted to study the alignment of stars when the girl experiences menarche because it is believed that her future can be predicted. The women of the family then gather in her home and scrub her in a  ritual bathing  ceremony. Her family then throws a familial party at which the girl wears white and may receive gifts. [ 44 ]


In  Ethiopia ,  Beta Jewish  women were separated from male society and sent to menstruation huts during menarche and every menstruation following as the blood associated with menstruation in the Beta Jewish culture was  believed to be impure . The Beta Jews built their villages surrounding and near bodies of water specifically for their women to have a place to clean themselves. The menstruation huts were built close to these bodies of water. [ 48 ]