Teratomas are also classified by their content; a solid teratoma contains only tissues (perhaps including more complex structures); a cystic teratoma contains only pockets of fluid or semifluid such as  cerebrospinal fluid ,  sebum , or fat; a mixed teratoma contains both solid and cystic parts. Cystic teratomas usually are grade 0 and, conversely, grade 0 teratomas usually are cystic.


Grades 0, 1, and 2 pure teratomas have the potential to become malignant (grade 3), and malignant pure teratomas have the potential to  metastasize .  These rare forms of teratoma with malignant transformation may contain elements of somatic (not germ cell) malignancy such as  leukemia ,  carcinoma , or  sarcoma . [ 35 ]
A teratoma may contain elements of other germ cell tumors, in which case it is not a pure teratoma, but rather is a mixed  germ cell tumor  and is malignant.  In infants and young children, these elements usually are  endodermal sinus tumor , followed by  choriocarcinoma .  Finally, a teratoma can be pure and not malignant yet highly aggressive;  this is exemplified by growing teratoma syndrome, in which chemotherapy eliminates the malignant elements of a mixed tumor, leaving pure teratoma, which paradoxically begins to grow very rapidly. [ 36 ]


A "benign" grade 0 (mature) teratoma nonetheless has a risk of malignancy.  Recurrence with malignant  endodermal sinus tumor  has been reported in cases of formerly benign mature teratoma, [ 37 ] [ 38 ]  even in fetiform teratoma and fetus in fetu. [ 39 ] [ 40 ]   Squamous cell carcinoma  has been found in a mature cystic teratoma at the time of initial surgery. [ 41 ]  A grade 1 immature teratoma that appears to be benign (e.g., because AFP is not elevated) has a much higher risk of malignancy, and requires adequate follow-up. [ 42 ] [ 43 ] [ 44 ] [ 45 ]
This grade of teratoma also may be difficult to diagnose correctly.  It can be confused with other small round cell neoplasms such as neuroblastoma, small cell carcinoma of hypercalcemic type, primitive neuroectodermal tumor, Wilm's tumor, desmoplastic small round cell tumor, and non-Hodgkin  lymphoma . [ 46 ]


A teratoma with malignant transformation  is a very rare form of teratoma that may contain elements of somatic malignant tumors such as leukemia, carcinoma, or sarcoma. [ 35 ]  Of 641 children with pure teratoma, nine developed TMT: [ 47 ]  five carcinoma, two  glioma , and two embryonal carcinoma (here, these last are classified among germ cell tumors).


Extraspinal  ependymoma , usually considered to be a glioma (a type of nongerm cell tumor), may be an unusual form of mature teratoma. [ 48 ]


The treatment of choice is complete surgical removal ( i.e.,  complete resection). [ 49 ] [ 50 ]  Teratomas are normally well-encapsulated and noninvasive of surrounding tissues, hence they are relatively easy to resect from surrounding tissues. Exceptions include teratomas in the brain, and very large, complex teratomas that have pushed into and become interlaced with adjacent muscles and other structures.


Prevention of recurrence does not require  en bloc  resection of surrounding tissues.


For malignant teratomas, usually, surgery is followed by chemotherapy.


Teratomas that are in surgically inaccessible locations, or are very complex, or are likely to be malignant (due to late discovery and/or treatment) sometimes are treated first with chemotherapy.  [ citation needed ]


Although often described as benign, a teratoma does have malignant potential.  A UK study of 351 infants and children diagnosed with "benign" teratoma reported 227 with MT, 124 with IT.  Five years after surgery, event-free survival was 92.2% and 85.9%, respectively, and overall survival was 99% and 95.1%. [ 51 ]   A similar study in Italy reported on 183 infants and children diagnosed with teratoma.  At 10 years after surgery, event-free and overall survival were 90.4% and 98%, respectively. [ 52 ]


Depending on which tissue(s) it contains, a teratoma may secrete a variety of chemicals with systemic effects. Some teratomas secrete the "pregnancy hormone"  human chorionic gonadotropin  (βhCG), which can be used in clinical practice to monitor the successful treatment or relapse in patients with a known HCG-secreting teratoma. This hormone is not recommended as a diagnostic marker, because most teratomas do not secrete it. Some teratomas secrete  thyroxine , in some cases to such a degree that it can lead to clinical  hyperthyroidism  in the patient. Of special concern is the secretion of  alpha-fetoprotein  (AFP); under some circumstances, AFP can be used as a diagnostic marker specific for the presence of  yolk sac  cells within the teratoma.  These cells can develop into a frankly malignant tumor known as  yolk sac tumor  or  endodermal sinus tumor .


Adequate follow-up requires close observation, involving repeated physical examination, scanning (ultrasound, MRI, or CT), and measurement of AFP and/or βhCG. [ 53 ] [ 54 ]


Embryonal teratomas most commonly occur in the sacrococcygeal region;  sacrococcygeal teratoma  is the single most common tumor found in newborn humans.


Of teratomas on the skull sutures, about 50% are found in or adjacent to the  orbit . [ 56 ]  Limbal dermoid is a  choristoma , not a teratoma.


Teratoma qualifies as a  rare disease , but is not extremely rare.  Sacrococcygeal teratoma alone is diagnosed at birth in one out of 40,000 humans.  Given the current human population and birth rate, this equals five per day or 1800 per year.  Add to that number sacrococcygeal teratomas diagnosed later in life, and teratomas in other locales, and the  incidence  approaches 10,000 new diagnoses of teratoma per year. [ citation needed ]


Ovarian teratomas have been reported in  mares , [ 57 ]
 mountain lions , [ 58 ] [ 59 ]  and canines. [ 60 ]  Teratomas also occur, rarely, in other species. [ 61 ]


Pluripotent stem cells including human induced pluripotent stem cells have a unique property of being able to generate teratomas when injected in rodents in the research laboratory. [ 62 ]  The roots of this observation has been attributed to  Leroy Stevens  of the  Jackson Laboratory . [ 63 ]  In 1970, Stevens noticed that the cell populations that gave rise to teratomas were very similar to the cells of very early embryos.
For this reason, the so-called "teratoma assay" is one of the gold-standard validation assays for pluripotent stem cells. [ 64 ]  Because differentiated human pluripotent stem cells are being developed as the basis for numerous regenerative medicine therapies, there is concern that residual undifferentiated stem cells could lead to teratoma formation in injected patients, and researchers are working to develop methods to address this concern. [ 65 ]


New research has looked at utilizing the human teratoma in chimeric animal studies as a promising platform for modeling multi-lineage human development, pan-tissue functional genetic screening, and tissue engineering. [ 66 ]


This article incorporates  public domain material  from  Dictionary of Cancer Terms .  U.S. National Cancer Institute .


Tocolytics  (also called  anti-contraction medications  or  labor suppressants ) are medications used to suppress  premature labor  (from Greek τόκος  tókos , " childbirth ", and λύσις  lúsis , "loosening"). Preterm birth accounts for 70% of neonatal deaths. [ 1 ]  Therefore, tocolytic therapy is provided when delivery would result in  premature birth , postponing delivery long enough for the administration of  glucocorticoids , which accelerate fetal lung maturity but may require one to two days to take effect.


Commonly used tocolytic medications include  β 2  agonists ,  calcium channel blockers ,  NSAIDs , and  magnesium sulfate . These can assist in delaying preterm delivery by suppressing uterine muscle contractions and their use is intended to reduce fetal  morbidity  and  mortality  associated with preterm birth. [ 2 ]  The suppression of contractions is often only partial and tocolytics can only be relied on to delay birth for a matter of days. Depending on the tocolytic used, the pregnant woman or fetus may require monitoring (e.g., blood pressure monitoring when  nifedipine  is used as it reduces blood pressure;  cardiotocography  to assess fetal well-being). In any case, the risk of preterm labor alone justifies hospitalization.


Tocolytics are used in preterm labor, which refers to when a baby is born too early before 37 weeks of pregnancy. As  preterm birth  represents one of the leading causes of neonatal morbidity and mortality, the goal is to prevent neonatal morbidity and mortality through delaying delivery and increasing  gestational age  by gaining more time for other management strategies like  corticosteroids  therapy that may help with fetus lung maturity. [ 3 ] [ 4 ]  Tocolytics are considered for women with confirmed preterm labor between 24 and 34 weeks of gestation age and used in conjunction with other therapies that may include corticosteroids administration, fetus  neuroprotection , and safe transfer to facilities. [ 5 ]


There is no clear  first-line  tocolytic agent. [ 6 ] [ 7 ]  Current evidence suggests that first line treatment with β 2  agonists, calcium channel blockers, or NSAIDs to prolong pregnancy for up to 48 hours is the best course of action to allow time for glucocorticoid administration. [ 1 ]


Various types of agents are used, with varying success rates and side effects. Some medications are not specifically approved by the  U.S. Food and Drug Administration  (FDA) for use in stopping uterine contractions in preterm labor, instead being used  off-label . [ citation needed ]


According to a 2022 Cochrane review, the most effective tocolytics for delaying preterm birth by 48 hours, and 7 days were the nitric oxide donors, calcium channel blockers, oxytocin receptor antagonists and combinations of tocolytics. [ 8 ]


Calcium-channel blockers  (such as  nifedipine ) and  oxytocin antagonists  (such as  atosiban ) may delay delivery by 2 to 7 days, depending on how quickly the medication is administered. [ 45 ]   NSAIDs  (such as  indomethacin ) and  calcium channel blockers  (such as  nifedipine ) are the most likely to delay delivery for 48 hours, with the least amount of maternal and neonatal side effects. [ 46 ]  Otherwise, tocolysis is rarely successful beyond 24 to 48 hours because current medications do not alter the fundamentals of labor activation. [ 47 ]  However, postponing premature delivery by 48 hours appears sufficient to allow pregnant women to be transferred to a center specialized for management of preterm deliveries, and thus administer corticosteroids for the possibility to reduce neonatal organ immaturity. [ 46 ]


The efficacy of  β-adrenergic agonists , atosiban, and  indomethacin  is a decreased  odds ratio  (OR) of delivery within 24 hours of 0.54 (95%  confidence interval  (CI): 0.32-0.91) and 0.47 within 48 hours (OR 0.47, 95% CI: 0.30-0.75). [ 6 ]


Antibiotics were thought to delay delivery, but no studies have shown any evidence that using antibiotics during preterm labor effectively delays delivery or reduces neonatal morbidity. [ 41 ]  Antibiotics are used in people with  premature rupture of membranes , but this is not characterized as tocolysis. [ 48 ]


In addition to drug-specific contraindications, [ 41 ]  several general factors may contraindicate delaying childbirth with the use of tocolytic medications.


Most tocolytics are currently being used off-label. The future direction of the development of tocolytics agents should be directed toward better efficacy in intentionally prolonging pregnancy. This will potentially result in less maternal, fetal, and neonatal adverse effects when delaying preterm childbirth. A few tocolytic alternatives worth pursuing include  Barusiban , a last generation of oxytocin receptor antagonists, as well as  COX-2 inhibitors . [ 50 ]  More studies on the use of multiple tocolytics must be directed to research overall health outcomes rather than solely pregnancy prolongation. [ 51 ]


Trial of labor after caesarean (TOLAC)  is the term for an attempted birth in a patient who has had a previous  caesarean section . It may result in a successful  VBAC  (vaginal birth after caesarean) or a repeat caesarean section. In approximately 20-40% of TOLACs, a caesarean is performed. TOLAC is recommended when a patient has had one previous caesarean section using a low transverse uterine incision.  The main risks of TOLAC are emergency caesarean section and  uterine rupture . [ 1 ] [ 2 ]


Twilight sleep  (English translation of the German word  Dämmerschlaf ) [ 1 ] [ 2 ]  is an  amnesic  state characterized by insensitivity to pain with or without the loss of consciousness, induced by an injection of  morphine  and  scopolamine , with the purpose of  pain management during childbirth . [ 3 ]  The obstetric method originated in Germany and gained large popularity in New York City in the early 20th century. [ 4 ]


In the Freiburg technique, considered the gold standard of twilight birth, patients were first given an  intramuscular injection  of  1 ⁄ 150   grain  (0.432  mg ) of  scopolamine  and  1 ⁄ 2  grain (32.4 mg) of  morphine . Forty five minutes later, a second scopolamine injection of the same dosage was administered. [ 4 ]  A memory test was then given, and subsequent smaller doses of scopolamine were given based on the individual's performance on the memory tests. [ 4 ]  When performed properly, the drug combination caused a drowsy state and relieved the pain only partially, whilst creating  amnesia  such that the woman giving birth sometimes would not remember any pain, although these results were variable. [ 4 ] [ 5 ] [ 6 ]  Because of how variable the scopolamine dosages are between patients, and the need for accurate assessment of performance on the memory test, the twilight sleep method required skillful, well-trained practitioners for proper execution. [ 7 ]


To effectively keep women in an amnesic state,  sensory isolation  was necessary. [ 7 ]  Women gave birth in a darkened room, and the  birth attendants  wore uniforms designed to minimize noise. [ 4 ]  Women were sometimes blind-folded, had their ears plugged with oil-soaked cotton, or were tied to padded beds with leather straps to "promote sleep." [ 6 ] [ 8 ]  Sensory deprivation also prevented  delirium , one of the adverse side effects of scopolamine. [ 7 ]


Prior to the 20th century, childbirth predominantly happened in the home, without access to any medical interventions for  pain management . [ 8 ]  Doctors (primarily, if not all men) were now managing the vast majority of childbirths as opposed to midwives or Doulas. Many women were fearful of the process of giving birth, creating a large desire for pain management. [ 4 ]  But despite the demands of female patients, little relief was offered before the mid-19th century. Chemical  anesthesia  during labor was first introduced in 1847, receiving support from women and reluctance from physicians. [ 4 ]  The legacy of the Bible in the  Anglo-American  medical community was clear. While pain relief was seen as a necessary part of surgery, many physicians viewed painful childbirth as a natural, divinely ordained punishment for  Eve ’s behavior in the  Garden of Eden . [ 4 ]  Anesthesia's use was popularized in 1853 by  Queen Victoria ’s decision to use  chloroform  for pain relief during the birth of her eighth child,  Prince Leopold, Duke of Albany . [ 4 ]


In 1899, a Dr Schneiderlin recommended the use of  hyoscine  and morphine for surgical anesthesia, and it began to be used as such sporadically. [ 3 ] [ 9 ]  The use of this combination to ease birth was first proposed by Austrian physician Richard von Steinbuchel in 1902, before being picked up and further developed by Carl Gauss and Bernhardt Kronig in  Freiburg , Germany, beginning in 1903. [ 10 ] [ 8 ]  The method came to be known as  "Dämmerschlaf"  ("twilight sleep") or the "Freiburg method" when performed according to Gauss and Kronig's specific technique. [ 3 ] [ 10 ]  Gauss and Kronig's research showed that the use of  scopolamine  during childbirth resulted in fewer complications and a faster recovery. The two presented their findings on the use of scopolamine during childbirth at the 1906 National Obstetrics Conference in Berlin, Germany. [ 8 ]  They recorded preferred dosages and adverse side effects of scopolamine, which included slowed pulse,  bradypnea ,  delirium ,  dilated pupils ,  flushed skin , and thirst. [ 7 ] [ 8 ]


Its usage spread slowly, and different clinics experimented with different dosages and ingredients. By 1907, Gauss was performing the Freiburg method on all of his pregnant patients, and wealthy German women began to travel to Freiburg for childbirth to receive Kronig and Gauss's twilight sleep method. [ 8 ]  The Women's Clinic of the  State University of Baden , where Gauss was a physician, had the city's lowest rates of maternal and neonatal mortality, further increasing the procedure's popularity. [ 8 ]  Eventually, wealthy pregnant women from the United States began traveling to Germany to receive twilight sleep during childbirth. [ 8 ]


A June 1914  McClure's Magazine  article titled, "Painless Childbirth" published by Marguerite Tracy and Constance Leupp about twilight sleep was instrumental in increasing awareness of the procedure in the United States. [ 4 ]  The article garnered a massive public response, prompting thousands of women to write the magazine asking for information about doctors able to perform the method. [ 7 ]  In the year after the publication of the  McClure  article, several books such as  Motherhood without Pain  were published that universally praised the procedure. [ 6 ]  Newspapers and magazines began pressuring American  obstetricians  to adopt the method of pain management in their own clinics. [ 8 ]  Twilight sleep gained a " faddish " popularity in New York City from 1914 to 1916. [ 7 ]


In 1915, the  New York Times  published an article on twilight sleep and the work of Hanna Rion Ver Beck, who had recently written a book entitled  The Truth About Twilight Sleep . In that article, Beck said that the consensus of 69 medical reports she had looked at said that "scopolamin-morphin is without danger to the child". [ 10 ]


Despite its popularity among patients, twilight sleep faced serious resistance from American doctors. Many physicians accused Gauss and Kronig of  propagandizing  women for financial gain. Because the treatment's greatest popularity overlapped with  World War I , women who advocated for the German technique were also accused of being disloyal to the United States. [ 4 ]


The use of twilight sleep began to decline in the United States after 1916 due to a number of factors. In the setting of New York City, it was extremely difficult to perform properly according to the Freiburg method. The dosages of  morphine  and  scopolamine  needed to be precise to avoid overdose, and NYC hospitals typically lacked the private, quiet birthing rooms like those used in Freiburg for sensory isolation. [ 7 ]  At its peak, there was such demand from women for twilight sleep that many physicians who were not adequately trained in the technique felt that the success of their obstetric practices depended on offering it. [ 4 ]  Thus, many untrained  nurses  and physicians were administering morphine and scopolamine at improper dosages, leading to a high rate of errors. [ 8 ]  Also contributing was the fact that twilight sleep did not actually cause a painless childbirth—the scopolamine produced amnesia, so the user did not remember the pain.


Twilight sleep spread in popularity in New York through a grassroots female-led campaign that was closely connected to the  first-wave feminism  movement. [ 6 ] [ 7 ]  Many of those active in the campaign were also suffragists, and they used techniques learned in the  suffrage movement  to increase awareness of twilight sleep. [ 7 ]


The procedure was initially heralded as the dawning of "a new era for woman and through her for the whole human race." [ 10 ]  Advocates of twilight birth, including Hanna Rion, saw the fight for pain management in childbirth as strongly connected to the fight for  gender equality . They described childbirth as "unnatural" and "unnecessary" and believed that male physicians did not adequately recognize the difficulties of maternity. [ 4 ]  Twilight sleep was seen as liberating women from the danger and pain imposed on them by their own bodies. [ 4 ]


Early feminists in  Manhattan  formed the National Twilight Sleep Association in 1914, which advocated for wider use. They organized pro-twilight sleep materials, lectures, and encouraged local New York physicians to offer the practice; articles appeared in the  New York Times ,  The Ladies' Home Journal , and  Reader's Digest  praising twilight birth. [ 5 ]  A  moving picture  showing the procedure, one of the first medical movies, was also created and screened for interested women. [ 11 ] [ 12 ]  Prominent NTSA member Mary Boyd's lectures about twilight sleep would draw crowds of nearly 300 women. She would end her lectures with the campaign's popular saying: “You women… will have to fight for it, for the mass of doctors are opposed to it.” [ 7 ]  Boyd and Tracy saw twilight sleep as a turning point in medicine, describing it as the “first time… that the whole body of patients have risen to dictate to the doctors.” [ 13 ]


The campaign dwindled after one of its leaders,  Frances X. Carmody, [ 14 ]  died of  hemorrhage  giving birth while using twilight sleep, though her husband and doctor asserted that her death was unrelated to the use of twilight sleep. [ 5 ] [ 8 ]


While twilight sleep began to wane in popularity after 1915, it permanently altered  obstetric  care and created irrevocable changes in the role of obstetricians in the United States. Obstetricians could no longer have a financially viable practice that did not include  pain management during childbirth . [ 4 ]  The use of morphine and scopolamine in twilight birth also positioned drug intervention as the main measure used in pain management during labor. [ 4 ]  Because twilight birth was performed in a hospital setting, it greatly contributed to changing childbirth from a home event to a medicalized hospital procedure. [ 4 ] [ 8 ]  The twilight birth fad accelerated the decrease in perceived importance of  midwives  and presented male physicians as those best qualified to assist in delivery, giving doctors more control over the birthing process. [ 4 ] [ 7 ]  The twilight birth movement also illustrates the power of public demand and media coverage in shaping the popularity of certain obstetric techniques. [ 7 ]


Uterine contractions  are  muscle contractions  of the  uterine smooth muscle  that can occur at various intensities in both the non-pregnant and pregnant uterine state. The non-pregnant uterus undergoes small, spontaneous contractions in addition to stronger, coordinated contractions during the  menstrual cycle  and orgasm. Throughout  gestation , [ 1 ]  the uterus enters a state of uterine quiescence due to various neural and hormonal changes. During this state, the uterus undergoes little to no contractions, though spontaneous contractions still occur for the uterine myocyte cells to experience  hypertrophy . [ 1 ]  The pregnant uterus only contracts strongly during orgasms,  labour , and in the postpartum stage to return to its natural size. [ 2 ]


Uterine contractions that occur throughout the  menstrual cycle , also termed  endometrial waves  or  contractile waves , [ 3 ]  appear to involve only the sub- endometrial  layer of the  myometrium . [ 3 ]


In the early  follicular phase , uterine contractions in the non-pregnant woman occur 1–2 times per minute and last 10–15 seconds with a low intensity of usually 30  mmHg  or less. This sub- endometrial  layer is rich in  estrogen  and  progesterone  receptors. [ 3 ]  The frequency of contractions increases to 3–4 per minute towards  ovulation . During the  luteal phase , the frequency and intensity decrease, possibly to facilitate any  implantation .


If implantation does not occur, the frequency of contractions remains low; but at  menstruation  the intensity increases dramatically to between 50 and 200  mmHg  producing labor-like contractions. [ 3 ]  These contractions are sometimes termed  menstrual cramps , [ 4 ]  although that term is also used for  menstrual pain  in general. These contractions may be uncomfortable or even painful, [ 5 ]  but they are generally significantly less painful than contractions during labour. Painful contractions are called  dysmenorrhea .


A shift in the  myosin  expression of the  uterine smooth muscle  has been hypothesized as arising for changes in the directions of uterine contractions during the menstrual cycle. [ 3 ]


Uterine contractions are a vital part of natural  childbirth , [ 6 ]  which occur during the process of labour and delivery, (typically this excludes  caesarean section ). These labour contractions are characterized by their rhythmic tightening and relaxation of the  myometrium , the most prominent uterine muscle. Labour contractions primarily serve the purpose of opening and dilating the  cervix , [ 7 ]  which leads to the assisting of the passage of the baby through the  vaginal canal  during the first stage of labour.


Throughout pregnancy, the uterus experiences motor denervation, thus inhibiting spontaneous contractions. The remaining contractions are predominantly hormonally controlled. The decrease in the coordination of uterine smooth muscles cells reduces the effectiveness of contractions, causing the uterus to enter a state of uterine quiescence. [ 8 ]  During the beginning of labour, contractions may initially be intermittent and irregular, [ 7 ]  but will transition into a more coordinated pattern as the labour progresses. [ 7 ]  This transition is governed by various myogenic, neurogenic, and hormonal factors working together. [ 8 ]  As labour progresses, contractions will typically increase in frequency and intensity, which leads to a significant rise in intrauterine pressure. [ 7 ]


Otherwise, not all contractions experienced by pregnant individuals are indications of the beginning of labour. Some women experience what are commonly called  Braxton Hicks contractions  before their initial due date, which are characterized as “false labour." Though similar to labour uterine contractions, these contractions do not play a prominent role in cervical dilation or the progression of childbirth.


The  hormone  oxytocin has been identified as inducing uterine contractions, and labour in general. [ 9 ]  Oxytocin is produced by the body naturally and since the 1950s has also been available in  synthetic   pharmaceutical form . [ 10 ] [ 11 ]   In either form, oxytocin stimulates uterine contractions to accelerate the process of  childbirth . Production and secretion of oxytocin is controlled by a  positive feedback  mechanism, where its initial release, either naturally or in pharmaceutical form, stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the duration, intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases.


The concentration of prostaglandins in the  blood plasma  and  amniotic fluid  increases during labor. [ 5 ]  These  inflammatory mediators  encourage myometrial contractions to induce labor. [ 5 ]  Prostaglandins are also related to the changes in  gap junction  formation and  connexin-43  expression during labor. [ 9 ]


Uterine and  vaginal contractions  usually take place during female  sexual stimulation , including  sexual arousal , and  orgasm . [ 12 ]


Uterine contractions can be  monitored  by  cardiotocography , in which a device is affixed to the skin of the mother or directly to the fetal scalp. The pressure required to flatten a section of the uterine wall correlates with the internal pressure, thereby providing an estimate of it. [ 13 ]


A type of monitoring technology under development at  Drexel University  embeds conductive threads in the knitted fabric of a bellyband. When the fibers stretch in response to a contraction, the threads function like an antenna, and send the signals they pick up to an embedded RFID ( radio-frequency identification  device) chip that reports the data. [ 14 ]


The  resting membrane potential  (V rest ) of uterine smooth muscle has been recorded to be between −35 and −80  mV . [ 3 ]  As with the resting membrane potential of other cell types, it is maintained by a  Na + /K +  pump  that causes a higher concentration of  Na +  ions in the extracellular space than in the  intracellular space , and a higher concentration of  K +  ions in the intracellular space than in the extracellular space. Subsequently, having  K +  channels  open to a higher degree than  Na +  channels  results in an overall  efflux  of positive ions, resulting in a negative potential.


This resting potential undergoes rhythmic oscillations, which have been termed  slow waves , and reflect intrinsic activity of  slow wave potentials . [ 3 ]  These slow waves are caused by changes in the distribution of  Ca 2+ , Na + , K +  and  Cl −  ions between the intracellular and extracellular spaces, which, in turn, reflects the permeability of the plasma membrane to each of those ions. [ 3 ]  K +  is the major ion responsible for such changes in  ion flux , reflecting changes in various K +  channels. [ 3 ]


As the uterus becomes essentially denervated during gestation, it is unlikely that any coordinated nervous regulation of the myometrium is centrally orchestrated. [ 15 ]


The  excitation-contraction coupling  of the uterine smooth muscle is also very similar to that of other  smooth muscles  in general, with intracellular increase in  calcium  (Ca 2+ ) leading to contraction.


Nitric oxide (NO) is particularly effective in relaxing the myometrium and in fact has a lower inhibitory concentration 50% (Ki) in human than guinea pig or non-human primate myometrium. [ 15 ]


Uterine smooth muscle mechanisms of relaxation differ significantly from those of other human smooth muscles. [ 15 ]  Removal of Ca 2+  after contraction induces relaxation of the smooth muscle, and restores the molecular structure of the  sarcoplasmic reticulum  for the next contractile stimulus. [ 3 ]


Ethically donated human uterine tissues can be used to measure uterine contractility  ex vivo . In these experiments, sections of  myometrium  are set up in an  organ bath  system that to measure changes in isometric force production. Following functional checks to ensure the tissue is physiologically active, compounds can be added to the organ bath in increasing concentrations to create a cumulative concentration-response curve (CCRC).


A key advantage of measuring uterine contractility  ex vivo  is the ability to eliminate species differences. For example, while magnesium reduces myometrial contractility in  animal studies  and  in vitro , it does not demonstrate the same effect in  clinical studies . [ 16 ]  And while the peptide hormone  relaxin  has been shown to inhibit uterine contractility in rats, mice, and pigs, it does not prevent uterine contractility in humans. [ 17 ]


Uterine Tachysystole  is a condition of excessively frequent  uterine contractions  during pregnancy. [ 1 ]  It is most often seen in  induced or augmented labor , though it can also occur during  spontaneous labor , [ 2 ]  and this may result in fetal  hypoxia  and  acidosis . This may have serious effects on both the mother and the fetus including  hemorrhaging  and  death . [ citation needed ]  There are still major gaps in understanding treatment as well as clinical outcomes of this condition. [ 3 ]  Uterine tachysystole is defined as more than 5 contractions in 10 minutes, averaged over a 30-minute period. [ 1 ]


Excessive contractions may be a sign of  placental abruption  or obstructed labor potentially leading to Uterine Tachysystole. [ 3 ]  Fetal hypoxia is often associated with uterine tachysystole as well as  neonatal brachial plexus  injury. [ citation needed ]


Researchers have determined that uterine tachysystole is not able to be predicted by either demographic or clinical factors, [ 4 ]  but there are factors that may correlate with the diagnosis.  Misoprostol  use and  high-dose oxytocin  use positively correlate highly with uterine tachysystole. [ 5 ]  Oxytocin is suspected to be a contributor to abnormally increased uterine contractions and uterine tachysystole, but further research is needed for this suspicion to be confirmed. [ 6 ]  There has been practice of using  nipple stimulation  to induce labor. However, one study reveals that this may be dangerous because of the uncontrolled release of oxytocin which has shown to correlate to the onset of uterine tachysystole. [ 7 ]  Prostaglandins, commonly used for initial stages of labor induction or augmentation, have been associated with tachysystole as well as fetal distress. [ 8 ]


The presence of uterine  leiomyomas  have shown to correlate with the incidence of uterine tachysystole. [ 9 ]


Antepartum hemorrhage  and  chorioamnionitis  are potential pathological causes for spontaneous Uterine Tachysystole. [ citation needed ]  Previous  cesarean sections  could potentially be a precursor to future uterine tachysystole as well. [ citation needed ]  There are no confirmed significant predictors for this condition. [ 4 ]


The function of the  placenta  is to act as the lungs and be a vessel of  gas exchange  for the fetus as this is where oxygen is exchanged for carbon dioxide. [ 1 ]  In the absence of laboring and contracting, blood flow into the  intervillous space  results from  spiral arterial pressure  exceeding intramyometrial pressure, or uterine pressure. [ 1 ]  During a contraction, uterine blood flow becomes disrupted as myometrial pressure elevates to a higher level than spiral arterial pressure, and this disallows oxygen to reach the fetus through the placenta during these contractions. [ 1 ]  During normal labor contractions, there is adequate time for a fetus to recover its  levels of oxygenation  during the relaxation time between contractions. [ 3 ]


Contractions that are stronger than normal and have a shortened relaxation time disallow for the placenta to receive adequate levels of blood flow which likely leads to the fetus receiving lower levels of oxygen through the placenta. [ 3 ]  A contraction with 30 mmHg or more leads to reduced placental blood flow and a potentially hypoxic fetus. [ 3 ]  The duration of the contraction affects the length of time in which the spiral arteries are compressed, and the strength of the contraction affects the degree of arterial compression. [ 1 ]  Throughout the laboring processing, this leads to progressive decrease in fetal oxygen saturation and fetal intracerebral oxygen saturation [ 3 ]  as fetal hypoxia occurs when contractions are either too long or too strong. [ 1 ]


The fetal oxygen reserve functions to supply the fetus with the oxygen that it needs to maintain adequate oxygen levels during transient stages of decreased oxygen  partial pressure  such as during contractions so that the fetus is able to tolerate the contractions. [ 1 ]  This fetal oxygen reserve is effective during normal laboring, but as contractions become more frequent, there is less and less time for oxygen levels to be replenished which then leads to fetal hypoxia. This reduced relaxation period between contractions also results in an inability to clear  acidotic metabolites  from the cells which may lead to fetal  acidosis . [ 1 ]


Fetal pulse oximetry  gave researchers the means to quantify the effects that result from uterine tachysystole. [ 1 ]  In 2008, 1,493 contractions were studied across 30 patients. The conclusion of this study revealed that there is a 6% decrease in fetal partial pressure of oxygen every 8 minutes during uterine tachysystole. [ 1 ]  The fetus’ oxygen saturation levels begin to deplete within about 5 minutes of the onset of uterine tachysystole and their hypoxic states exacerbated until the UT was able to be stopped. [ 1 ]  Several other factors may worsen the clinical presentation of uterine tachysystole such as pregnancy or labor complications that compound hypoxia or acidosis in the fetus, a fetus with a already compromised baseline oxygenation due to  intrauterine growth restriction ,  oligohydramnios , and  cord compression , and preexisting  uteroplacental insufficiency  due to  hypertensive disorders ,  post-term pregnancy , or  diabetes . [ 1 ]


Uterine Tachysystole is diagnosed upon the presence of several different clinical presentations of a laboring patient. If a patient experiences any of the following presentations during labor, they may receive a diagnosis of Uterine Tachysystole: [ 1 ]


When fetal distress and hypoxia results from uterine tachysystole,  tocolytic  medications may be used to attempt to improve the baby’s oxygen levels. There is not sufficient research that gives a clear indication as to which tocolytic drug is safer for the patient. [ 3 ]  An  emergency delivery  or  cesarean section  may also be an effective treatment option, tocolytic drugs are very important in low-resource environments when a C-section may not be available. [ 3 ]  Methods such as inserting a  transcervical foley catheter  are also effective in reducing the incidence of uterine tachysystole. [ citation needed ]


Serious effects may result in hypoxic babies that suffer through Uterine Tachysystole such as  cerebral palsy ,  organ damage , acidemia/acidosis,  brain damage  and death. [ 3 ]  Some of these consequences may be life-long for the mother or the fetus. [ 1 ]  Newborns born to mothers that experiences tachysystole were two times as likely to be admitted into  NICU . [ 10 ]  There are also risks that are posed to the mother as well resulting from UT including increased C-section rates,  cervical laceration , placental abruption or uterine rupture (for women with history of C-sections), infection,  antepartum  or  postpartum  hemorrhage, increased risk of  amniotic fluid embolism , and death. [ citation needed ]


A study of 890 patients revealed that about 11.1% of the sample had a minimum of one episode of uterine tachysystole with the incidence being higher in non-whites. [ 10 ]  The adjusted  odds ratio  for UT in Hispanics was about 1.66 with a 95%  confidence interval  of 1.28-2.05, 1.58 for African Americans with a 95% confidence interval of about 1.05-2.38, and 1.51 for Asians with a 95% confidence interval of about 1.13-2.0. [ 10 ]  The subjects in the study with uterine tachysystole had a higher usage of  epidural analgesia  with 62.2% of those with UT having taken an epidural compared to the 40.9% of the subjects in the group without UT having taken an epidural (  p < 0.001 ). [ 10 ]  Uterine Tachysystole was found in higher rates among women who had yet to have previously born a viable child as well as in women carrying heavier fetuses. [ 10 ]


Further research is needed on Uterine Tachysystole with larger sample sizes of women. [ 3 ]  Future directions of research may include the measure of clinically relevant outcomes for the mother and the baby resulting from Uterine Tachysystole such as death, well-being, and safety of the mother and/or the baby. [ 3 ]  Future research on the administration of misoprostol is needed so that this medication may be able to be safely administered to induce labor while simultaneously minimizing the risk of developing Uterine Tachysystole. [ 4 ]


A  vertically transmitted infection  is an  infection  caused by  pathogenic bacteria  or  viruses  that use  mother-to-child transmission , that is,  transmission  directly from the mother to an  embryo ,  fetus , or baby during  pregnancy  or  childbirth . It can occur when the mother has a   pre-existing disease  or becomes infected during pregnancy. Nutritional deficiencies may exacerbate the risks of perinatal infections. Vertical transmission is important for the  mathematical modelling of infectious diseases , especially for diseases of animals with large litter sizes, as it causes a wave of new infectious individuals. [ 1 ]


Bacteria, viruses, and other organisms are able to be passed from mother to child. Several vertically transmitted infections are included in the  TORCH complex : [ 2 ]


Other infections include:


Hepatitis B  may also be classified as a vertically transmitted infection.  The  hepatitis B virus  is large and does not cross the placenta.  Hence, it cannot infect the fetus unless breaks in the  maternal-fetal barrier  have occurred, but such breaks can occur in bleeding during  childbirth  or  amniocentesis . [ 13 ]


The TORCH complex was originally considered to consist of the four conditions mentioned above, [ 14 ]  with the "TO" referring to  Toxoplasma . The four-term form is still used in many modern references, [ 15 ]  and the capitalization "ToRCH" is sometimes used in these contexts. [ 16 ]  The acronym has also been listed as TORCHES, for TOxoplasmosis, Rubella, Cytomegalovirus, HErpes simplex, and Syphilis. [ citation needed ]


A further expansion of this acronym, CHEAPTORCHES, was proposed by Ford-Jones and Kellner in 1995: [ 17 ]


The signs and symptoms of a vertically transmitted infection depend on the individual pathogen.  In the mother, it may cause subtle signs such as an  influenza-like illness , or possibly no symptoms at all.  In such cases, the effects may be seen first at birth. [ citation needed ]


Symptoms of a vertically transmitted infection may include fever and flu-like symptoms. The newborn is often  small for gestational age . A  petechial  rash on the skin may be present, with small reddish or purplish spots due to bleeding from capillaries under the skin. An enlarged liver and spleen ( hepatosplenomegaly ) is common, as is  jaundice . However, jaundice is less common in hepatitis B because a newborn's immune system is not developed well enough to mount a response against liver cells, as would normally be the cause of jaundice in an older child or adult.  Hearing impairment , eye problems,  mental retardation ,  autism , and death can be caused by vertically transmitted infections. [ citation needed ]


The genetic conditions of  Aicardi-Goutieres syndrome  are possibly present in a similar manner. [ 19 ] [ 20 ]


The main routes of transmission of vertically transmitted infections are across the  placenta  (transplacental) and across the  female reproductive tract  during childbirth. Transmission is also possible by breaks in the  maternal-fetal barrier  such by  amniocentesis [ 13 ]  or  major trauma .


The embryo and fetus have little or no  immune function . They depend on the immune function of their mother. Several  pathogens  can cross the  placenta  and cause perinatal infection. Often,  microorganisms  that produce minor illness in the mother are very dangerous for the developing embryo or fetus. This can result in  spontaneous abortion  or major  developmental disorders . For many infections, the baby is more at risk at particular stages of pregnancy. Problems related to perinatal infection are not always directly noticeable. [ citation needed ]


Apart from infecting the fetus, transplacental pathogens may cause  placentitis  (inflammation of the placenta) and/or  chorioamnionitis  (inflammation of the  fetal membranes ). [ citation needed ]


Babies can also become infected by their mothers during  birth . Some infectious agents may be transmitted to the embryo or fetus in the uterus, while passing through the birth canal, or even shortly after birth. The distinction is important because when transmission is primarily during or after birth, medical intervention can help prevent infections in the infant. [ citation needed ] During birth, babies are exposed to maternal  blood ,  body fluids , and to the maternal genital tract without the placental barrier intervening. Because of this, blood-borne microorganisms (hepatitis B, HIV), organisms associated with  sexually transmitted infections  (e.g.,  Neisseria gonorrhoeae  and  Chlamydia trachomatis ), and normal  fauna  of the  genitourinary tract  (e.g.,  Candida albicans ) are among those commonly seen in infection of newborns. [ citation needed ]


In the spectrum of  optimal virulence , vertical transmission tends to evolve benign  symbiosis , so is a critical concept for  evolutionary medicine . Because a pathogen's ability to pass from mother to child depends significantly on the hosts' ability to reproduce, pathogens' transmissibility tends to be inversely related to their virulence. In other words, as pathogens become more harmful to, and thus decrease the reproduction rate of, their host organism, they are less likely to be passed on to the hosts' offspring since they will have fewer offspring. [ 21 ]


Although HIV is sometimes transmitted through perinatal transmission, its virulence can be accounted for because its primary mode of transmission is not vertical. Moreover, medicine has further decreased the frequency of vertical transmission of HIV. The incidence of perinatal HIV cases in the United States has declined as a result of the implementation of recommendations on HIV counselling and voluntary testing practices and the use of  zidovudine  therapy by providers to reduce perinatal HIV transmission. [ 22 ]


The price paid in the evolution of symbiosis is, however, great:  for many generations, almost all cases of vertical transmission continue to be pathological—in particular if any other routes of transmission exist. Many generations of random mutation and selection are needed to evolve symbiosis. During this time, the vast majority of vertical transmission cases exhibit the initial virulence. [ citation needed ]


In  dual inheritance theory , vertical transmission refers to the passing of cultural traits from parents to children. [ 23 ]


When physical examination of the newborn shows signs of a vertically transmitted infection, the examiner may test blood, urine, and spinal fluid for evidence of the infections listed above. Diagnosis can be confirmed by culture of one of the specific pathogens or by increased levels of  IgM  against the pathogen. [ citation needed ]


A vertically transmitted infection can be called a  perinatal infection  if it is transmitted in the  perinatal period , which starts at  gestational ages  between 22 [ 24 ]  and 28 weeks [ 25 ]  (with regional variations in the definition) and ending seven completed days after birth. [ 24 ]


The term  congenital infection  can be used if the vertically transmitted infection persists after childbirth. [ citation needed ]


Some vertically transmitted infections, such as toxoplasmosis and syphilis, can be effectively treated with antibiotics if the mother is diagnosed early in her pregnancy. Many viral vertically transmitted infections have no effective treatment, but some, notably rubella and varicella-zoster, can be prevented by  vaccinating  the mother prior to pregnancy. [ citation needed ]


Pregnant women living in malaria-endemic areas are candidates for  malaria prophylaxis . It clinically improves the anemia and  parasitemia  of the pregnant women, and birthweight in their infants. [ 26 ]


If the mother has active herpes simplex (as may be suggested by a  pap test ), delivery by  Caesarean section  can prevent the newborn from contact, and consequent infection, with this virus. [ citation needed ]


IgG 2  antibody may play a crucial role in prevention of intrauterine infections and extensive research is going on for developing IgG 2 -based therapies for treatment and vaccination. [ 27 ]


Each type of vertically transmitted infection has a different prognosis. The stage of the pregnancy at the time of infection also can change the effect on the newborn. [ citation needed ]


Water birth  is  childbirth  that occurs in water, usually a birthing pool. It may include the use of water for relaxation and pain relief during the first stage of labour, birth into water in the second stage of labour, and the delivery of the placenta in the third stage of labour.


Approximately 10% of births in the UK take place in water, and approximately 20% of births include the use of water for pain relief. [ 1 ]  A cohort study carried out in the UK of 73,229 women concluded that there was no association with adverse fetal or maternal outcomes. [ 2 ]


Health policy in England stipulates women should be given the opportunity to labour in water through the publication of Intrapartum care guidelines issued in 2007 by the  National Institute for Health and Care Excellence (NICE) .  The  Royal College of Obstetricians and Gynaecologists  and the  Royal College of Midwives  have jointly supported labour and birthing in water, and encourage hospitals to ensure birth pools are available to all women. [ 3 ]


Birthing pools are available in many public hospitals in the UK. [ 4 ] [ 5 ] [ 6 ] [ 7 ] [ 8 ]


The  Royal Australian and New Zealand College of Obstetricians and Gynaecologists  supports the use of water immersion during labour within safety and clinical guidelines, noting that there is evidence of benefits to the mother and no evidence of adverse effects to the mother or baby. [ 9 ]  The New Zealand College of Midwives supports water immersion during labour when there are no factors that would prevent it, noting that there is no evidence for adverse fetal or maternal outcomes, but that further evidence is required for the delivery of the placenta. [ 10 ]  The  Australian College of Midwives  also supports immersion in water during labour and/or birth. [ 11 ]


Birthing pools are available at many public and private hospitals in Australia [ 12 ]  and New Zealand. [ 13 ] [ 14 ] [ 15 ]


Water birth is not commonly available in hospitals in the  United States , and American clinical opinion is generally skeptical of the practice. The  American College of Obstetricians and Gynecologists  does not recommend birthing in water, although its 2016 Committee Opinion on the matter states that immersion in water during the first stage of labour may be offered to women with uncomplicated pregnancies. [ 16 ]


In a 2005 commentary, the Committee on Fetus and Newborn of the  American Academy of Pediatrics  (AAP) released an analysis of the scientific literature regarding underwater births. The Committee noted several positive studies for underwater birth but went on to criticize them for lacking proper  scientific controls , a significant number of infant deaths and diseases, and the general lack of information to support the use of water births. [ 17 ]


Proponents believe  childbirth  in water results in a more relaxed, less painful experience. [ 18 ]  A 2018  Cochrane Review  of water immersion in the first stages of labour found evidence of fewer  epidurals  and few  adverse effects  but insufficient information regarding giving birth in water. [ 19 ]
A moderate to weak level of evidence indicates that water immersion during the  first stage of childbirth  reduces the pain of labour. [ 19 ]   A 2018  Cochrane Review  found that immersion at this stage reduces the use of  epidural   analgesia ; however, there is no clear evidence on the benefits of immersion for the  second stage of labour , namely delivery (sometimes called full water birth). [ 19 ]  There is no evidence of increased  adverse effects  for immersion during the first or second stages of labour. [ 19 ]


Water birth may offer perineal support for the mother, and some theorize that this may decrease the risk of tearing and reduce the use of  episiotomy . [ 20 ]  Evidence for this is not strong. [ 19 ]


A 2014 review reported that water immersion during the first stage of labour can reduce the length of that stage, labour pain, and the use of epidural or  spinal anaesthesia . It is also associated with a lower rate of  cesarean delivery  and  stress urinary incontinence  symptoms  42 days after delivery .  The review reported that immersion during labour did not appear to increase the rate of infections for the mother or the baby, and  Apgar  scores for the newborn infant were similar to those of conventional births. [ 21 ]


Waterbirth may lead to a higher rate of cord avulsion, or the snapping of the umbilical cord. [ 22 ]  Statements on water birth by peak gynaecological and midwifery bodies in the UK, Australia and New Zealand all stipulate that exclusion criteria apply for high risk births. [ 23 ] [ 24 ] [ 25 ]


There is limited evidence for some of the purported benefits of waterbirth.


A birth pool is a specially designed vessel for waterbirth. [ 26 ]  They are generally larger than bathtubs to enable buoyancy and freedom of movement during labour. [ 27 ]  A birth pool can either be permanently installed or portable.


Before birth pools became readily available there were many stories of women labouring and birthing in re-purposed tub-like products including animal watering troughs. [ 28 ]


The original circular birth pool used by  Michel Odent , the originator of the concept of birthing pools, at Pithiviers hospital in France in the early 1980s was 2 metres (6 ft 7 in) in diameter and 60 centimetres (24 in) deep, large enough to comfortably accommodate two people. [ 29 ]   Modern birth pools are somewhat smaller, with a diameter between 110–150 cm (43–59 in) and at least 50 cm (20 in), preferably 56 cm (22 in), of water. [ 30 ]


Menopause , also known as the  climacteric , is the time when  menstrual periods  permanently stop, marking the end of reproduction. [ 1 ] [ 6 ] [ 7 ]  It typically occurs between the ages of 45 and 55, although the exact timing can vary. [ 8 ]  Menopause is usually a natural change related to a decrease in circulating blood estrogen levels. [ 3 ]  It can occur earlier in those who  smoke tobacco . [ 2 ] [ 9 ]  Other causes include surgery that removes both  ovaries , some types of  chemotherapy , or anything that leads to a decrease in hormone levels. [ 10 ] [ 2 ]  At the physiological level, menopause happens because of a decrease in the ovaries' production of the hormones  estrogen  and  progesterone . [ 1 ]  While typically not needed, a diagnosis of menopause can be confirmed by measuring hormone levels in the blood or urine. [ 11 ]  Menopause is the opposite of  menarche , the time when a girl's periods start. [ 12 ]


In the years before menopause, a woman's periods typically become irregular, [ 13 ] [ 14 ]  which means that periods may be longer or shorter in duration or be lighter or heavier in the amount of flow. [ 13 ]  During this time, women often experience  hot flashes ; these typically last from 30 seconds to ten minutes and may be associated with shivering,  night sweats , and reddening of the skin. [ 13 ]  Hot flashes [ 13 ]  can recur for four to five years. [ 6 ]  Other symptoms may include  vaginal dryness , [ 15 ]  trouble sleeping, and mood changes. [ 13 ] [ 16 ]  The severity of symptoms varies between women. [ 6 ]
Menopause before the age of 45 years is considered to be "early menopause" and when ovarian failure/surgical removal of the ovaries occurs before the age of 40 years this is termed " premature ovarian insufficiency ". [ 17 ]


In addition to symptoms (hot flushes/flashes, night sweats, mood changes,  arthralgia  and vaginal dryness), the physical consequences of menopause include bone loss, increased central abdominal fat, and adverse changes in a woman's cholesterol profile and vascular function. [ 17 ]  These changes predispose postmenopausal women to increased risks of  osteoporosis  and bone fracture, and of  cardio-metabolic disease  ( diabetes  and  cardiovascular disease ). [ 17 ]


Medical professionals  often define menopause as having occurred when a woman has not had any menstrual bleeding for a year. [ 2 ]  It may also be defined by a decrease in  hormone  production by the  ovaries . [ 18 ]  In those who have had  surgery  to remove their  uterus  but still have functioning ovaries, menopause is not considered to have yet occurred. [ 17 ]  Following the removal of the uterus, symptoms of menopause typically occur earlier. [ 19 ]  Iatrogenic menopause occurs when both ovaries are surgically removed ( Oophorectomy ) along with uterus for medical reasons.


The primary indications for treatment of menopause are symptoms and prevention of bone loss. [ 20 ]  Mild symptoms may be improved with treatment. With respect to hot flashes, avoiding smoking, caffeine, and alcohol is often recommended; sleeping naked in a cool room and using a fan may help. The most effective treatment for menopausal symptoms is  menopausal hormone therapy  (MHT). [ 15 ] [ 20 ]  Non-hormonal therapies for hot flashes include  cognitive-behavioral therapy ,  clinical hypnosis ,  gabapentin ,  fezolinetant  or  selective serotonin reuptake inhibitors . [ 21 ] [ 22 ]  These will not improve symptoms such as joint pain or vaginal dryness which affect over 55% of women. [ 20 ]  Exercise may help with sleeping problems. Many of the concerns about the use of MHT raised by older studies are no longer considered barriers to MHT in healthy women. [ 20 ]  High-quality evidence for the effectiveness of  alternative medicine  has not been found. [ 6 ]


During early menopause transition, the  menstrual cycles  remain regular but the interval between cycles begins to lengthen. Hormone levels begin to fluctuate. Ovulation may not occur with each cycle. [ 23 ]


The term  menopause  refers to a point in time that follows one year after the last  menstruation . [ 23 ]  During the menopausal transition and after menopause, women can experience a wide range of symptoms. [ 13 ]  However, for women who enter the menopause transition without having regular menstrual cycles (due to prior surgery, other medical conditions or ongoing hormonal contraception) the menopause cannot be identified by bleeding patterns and is defined as the permanent loss of ovarian function. [ 20 ]


During the transition to menopause,  menstrual patterns  can show shorter cycling (by 2–7 days); [ 23 ]  longer cycles remain possible. [ 23 ]  There may be  irregular bleeding  (lighter, heavier, spotting). [ 13 ] [ 23 ]   Dysfunctional uterine bleeding  is often experienced by women approaching menopause due to the hormonal changes that accompany the menopause transition. Spotting or bleeding may simply be related to vaginal  atrophy , a benign sore ( polyp  or lesion), or may be a functional endometrial response. The  European Menopause and Andropause Society  has released guidelines for assessment of the  endometrium , which is usually the main source of spotting or bleeding. [ 24 ]


In post-menopausal women, however, any unscheduled vaginal  bleeding  is of concern and requires an appropriate investigation to rule out the possibility of malignant diseases.


Urogenital symptoms may appear during menopause and continue through  postmenopause  and include  painful intercourse ,  vaginal dryness  and  atrophic vaginitis  (thinning of the membranes of the  vulva , the  vagina , the  cervix  and the outer  urinary tract ). There may also be considerable shrinking and loss in elasticity of all of the outer and inner genital areas.  Urinary urgency  may also occur and  urinary incontinence  in some women. [ 23 ] [ 25 ]


The most common physical symptoms of menopause are heavy  night sweats , and  hot flashes  (also known as vasomotor symptoms). [ 26 ]  Sleeping problems and  insomnia  are also common. [ 27 ]  Other physical symptoms may be reported that are not specific to menopause but may be exacerbated by it, such as  lack of energy ,  joint soreness ,  stiffness ,  back pain , breast enlargement,  breast pain ,  heart palpitations ,  headache ,  dizziness ,  dry ,  itchy  skin, thinning,  tingling  skin,  rosacea ,  weight gain . [ 23 ] [ 28 ]


Psychological symptoms are often reported but they are not specific to menopause and can be caused by other factors. [ 29 ] [ 30 ]  They include  anxiety , poor memory, inability to concentrate, depressive mood,  irritability ,  mood swings , and less  interest in sexual activity . [ 23 ] [ 31 ] [ 13 ]


Menopause-related cognitive impairment  can be confused with the  mild cognitive impairment  that precedes  dementia . [ 32 ]  There is evidence of small decreases in verbal memory, on average, which may be caused by the effects of declining estrogen levels on the brain, [ 33 ]  or perhaps by reduced blood flow to the brain during  hot flashes . [ 34 ]  However, these tend to resolve for most women during the postmenopause. Subjective reports of memory and concentration problems are associated with several factors, such as lack of sleep, and stress. [ 30 ] [ 29 ]


Exposure to endogenous  estrogen  during reproductive years provides women with protection against  cardiovascular disease , which is lost around 10 years after the onset of menopause. The menopausal transition is associated with an increase in  fat mass  (predominantly in  visceral fat ), an increase in  insulin resistance ,  dyslipidaemia , and  endothelial dysfunction . [ 35 ]   Women with  vasomotor symptoms  during menopause seem to have an especially unfavorable cardiometabolic profile, [ 36 ]  as well as women with premature onset of menopause (before 45 years of age). [ 37 ]  These risks can be reduced by managing risk factors, such as tobacco smoking,  hypertension , increased  blood lipids  and body weight. [ 38 ] [ 39 ]


The annual rates of  bone mineral density  loss are highest starting one year before the final menstrual period and continuing through the two years after it. [ 40 ]  Thus, post menopausal women are at increased risk of  osteopenia ,  osteoporosis  and  fractures .


Menopause is a normal event in a woman's life and a natural part of aging. [ 25 ]  Menopause can also be induced early. [ 41 ]  Induced menopause occurs as a result of medical treatment such as  chemotherapy ,  radiotherapy ,  oophorectomy , or complications of  tubal ligation ,  hysterectomy , unilateral or bilateral salpingo-oophorectomy or  leuprorelin  usage. [ 42 ]


Menopause typically occurs at some point between 47 and 54 years of age. [ 8 ]  According to various data, more than 95% of women have their last period between the ages of 44–56 (median 49–50).  2% of women under the age of 40, 5% between the ages of 40–45 and the same number between the ages of 55–58 have their last bleeding. [ 43 ]  The average age of the last period in the United States is 51 years, in Russia is 50 years, in Greece is 49 years, in Turkey is 47 years, in Egypt is 47 years and in India is 46 years. [ 44 ]  Beyond the influence of genetics, these differences are also due to early-life environmental conditions [ 45 ]  and associated with epigenetic effects. [ 46 ]  The menopausal transition or perimenopause leading up to menopause usually lasts 3–4 years (sometimes as long as 5–14 years). [ 1 ] [ 14 ]


Undiagnosed and untreated  coeliac disease  is a risk factor for early menopause. Coeliac disease can present with several non-gastrointestinal symptoms, in the absence of gastrointestinal symptoms, and most cases escape timely recognition and go undiagnosed, leading to a risk of long-term complications. A strict  gluten-free diet  reduces the risk. Women with early diagnosis and treatment of coeliac disease present a normal duration of fertile life span. [ 47 ] [ 48 ]


Women who have undergone  hysterectomy  with ovary conservation go through menopause on average 1.5 years earlier than the expected age. [ 20 ]


In rare cases, a woman's ovaries stop working at a very early age, ranging anywhere from the age of  puberty  to age 40. This is known as  premature ovarian failure  or premature ovarian insufficiency (POI) and affects 1 to 2% of women by age 40. [ 49 ] [ 50 ] [ 51 ]  It is diagnosed or confirmed by high blood levels of  follicle stimulating hormone  (FSH) and  luteinizing hormone  (LH) on at least three occasions at least four weeks apart. [ 52 ]


Premature ovarian insufficiency may be related to an auto immune disorder and therefore might co-occur with other  autoimmune disorders  such as  thyroid  disease, [adrenal insufficiency], and  diabetes mellitus . [ 51 ]  Other causes include  chemotherapy , being a carrier of the  fragile X syndrome  gene, and  radiotherapy . [ 51 ]  However, in about 50–80% of cases of premature ovarian insufficiency, the cause is unknown, i.e., it is generally  idiopathic . [ 50 ] [ 52 ]


Early menopause can be related to  cigarette  smoking, higher  body mass index , racial and ethnic factors, illnesses, and the removal of the uterus. [ 53 ]


Menopause can be surgically induced by bilateral  oophorectomy  (removal of ovaries), [ 41 ]  which is often, but not always, done in conjunction with removal of the fallopian tubes ( salpingo-oophorectomy ) and uterus ( hysterectomy ). [ 54 ]  Cessation of menses as a result of removal of the ovaries is called "surgical menopause". Surgical treatments, such as the removal of ovaries, might cause periods to stop altogether. [ 55 ]  The sudden and complete drop in hormone levels may produce extreme withdrawal symptoms such as hot flashes, etc. The symptoms of early menopause may be more severe. [ 55 ]


Removal of the uterus  without  removal of the ovaries does  not  directly cause menopause, although pelvic surgery of this type can often precipitate a somewhat earlier menopause, perhaps because of a compromised blood supply to the ovaries. [ medical citation needed ]  The time between surgery and possible early menopause is due to the fact that ovaries are still producing hormones. [ 55 ]


The menopausal transition, and postmenopause itself, is a natural change, not usually a disease state or a disorder. The main cause of this transition is the natural depletion and aging of the finite amount of  oocytes  ( ovarian reserve ). This process is sometimes accelerated by other conditions and is known to occur earlier after a wide range of gynecologic procedures such as  hysterectomy  (with and without  ovariectomy ),  endometrial ablation  and  uterine artery embolisation . The depletion of the ovarian reserve causes an increase in circulating  follicle-stimulating hormone  (FSH) and  luteinizing hormone  (LH) levels because there are fewer  oocytes  and follicles responding to these hormones and producing estrogen. [ citation needed ]


The transition has a variable degree of effects. [ 56 ]


The stages of the menopause transition have been classified according to a woman's reported bleeding pattern, supported by changes in the pituitary  follicle-stimulating hormone  (FSH) levels. [ 57 ]


In younger women, during a normal  menstrual cycle  the ovaries produce  estradiol ,  testosterone  and  progesterone  in a cyclical pattern under the control of FSH and  luteinizing hormone  (LH), which are both produced by the  pituitary gland . During perimenopause (approaching menopause),  estradiol  levels and patterns of production remain relatively unchanged or may increase compared to young women, but the cycles become frequently shorter or irregular. [ 58 ]  The often observed increase in estrogen is presumed to be in response to elevated FSH levels that, in turn, is hypothesized to be caused by decreased feedback by  inhibin . [ 59 ]  Similarly, decreased inhibin feedback after  hysterectomy  is hypothesized to contribute to increased ovarian stimulation and earlier menopause. [ 60 ] [ 61 ]


The menopausal transition is characterized by marked, and often dramatic, variations in FSH and estradiol levels. Because of this, measurements of these hormones are  not  considered to be reliable guides to a woman's exact menopausal status. [ 59 ]


Menopause occurs because of the sharp decrease of estradiol and progesterone production by the ovaries. After menopause, estrogen continues to be produced mostly by  aromatase  in fat tissues and is produced in small amounts in many other tissues such as ovaries, bone, blood vessels, and the brain where it acts locally. [ 62 ]  The substantial fall in circulating estradiol levels at menopause impacts many tissues, from brain to skin.


In contrast to the sudden fall in estradiol during menopause, the levels of total and free testosterone, as well as  dehydroepiandrosterone sulfate  (DHEAS) and  androstenedione  appear to decline more or less steadily with age. An effect of natural menopause on circulating  androgen  levels has not been observed. [ 63 ]  Thus specific tissue effects of natural menopause cannot be attributed to loss of androgenic hormone production. [ 64 ]


Hot flashes and other vasomotor and body symptoms accompanying the menopausal transition are associated with estrogen insufficiency and changes that occur in the brain, primarily the  hypothalamus  and involve complex interplay between the neurotransmitters  kisspeptin ,  neurokinin B , and  dynorphin , which are found in KNDy neurons in the infundibular nucleus. [ 65 ]


Decreased inhibin feedback after  hysterectomy  is hypothesized to contribute to increased ovarian stimulation and earlier menopause. Hastened ovarian aging has been observed after  endometrial ablation . While it is difficult to prove that these surgeries are causative, it has been hypothesized that the  endometrium  may be producing endocrine factors contributing to the endocrine feedback and regulation of the ovarian stimulation. Elimination of these factors contributes to faster depletion of the ovarian reserve. Reduced blood supply to the ovaries that may occur as a consequence of hysterectomy and  uterine artery embolisation  has been hypothesized to contribute to this effect. [ 60 ] [ 61 ]


Impaired  DNA  repair mechanisms may contribute to earlier depletion of the ovarian reserve during aging. [ 66 ]  As women age, double-strand breaks accumulate in the DNA of their primordial follicles. Primordial follicles are immature primary oocytes surrounded by a single layer of granulosa cells. An enzyme system is present in oocytes that ordinarily accurately repairs DNA double-strand breaks. This repair system is called " homologous recombinational  repair", and it is especially effective during meiosis. Meiosis is the general process by which germ cells are formed in all sexual eukaryotes; it appears to be an adaptation for efficiently removing damages in germ line DNA. [ 67 ]


Human primary oocytes are present at an intermediate stage of meiosis, termed prophase I (see  Oogenesis ). Expression of four key DNA repair genes that are necessary for homologous recombinational repair during meiosis (BRCA1, MRE11, Rad51, and ATM) decline with age in oocytes. [ 66 ]  This age-related decline in ability to repair DNA double-strand damages can account for the accumulation of these damages, that then likely contributes to the depletion of the ovarian reserve.


Ways of assessing the impact on women of some of these menopause effects, include the  Greene climacteric scale  questionnaire, [ 68 ]  the Cervantes scale [ 69 ]  and the Menopause rating scale. [ 70 ]


The term "perimenopause", which literally means "around the menopause", refers to the menopause transition years before the date of the final episode of flow. [ 1 ] [ 14 ] [ 71 ] [ 72 ]  According to the  North American Menopause Society , this transition can last for four to eight years. [ 73 ]  The  Centre for Menstrual Cycle and Ovulation Research  describes it as a six- to ten-year phase ending 12 months after the last menstrual period. [ 74 ]


During perimenopause,  estrogen  levels average about 20–30% higher than during premenopause, often with wide fluctuations. [ 74 ]  These fluctuations cause many of the physical changes during perimenopause as well as menopause, especially during the last 1–2 years of perimenopause (before menopause). [ 71 ] [ 75 ]  Some of these changes are  hot flashes ,  night sweats , difficulty sleeping, mood swings,  vaginal dryness  or  atrophy ,  incontinence ,  osteoporosis , and heart disease. [ 74 ]  Perimenopause is also associated with a higher likelihood of depression (affecting from 45 percent to 68 percent of perimenopausal women), which is twice as likely to affect those with a history of depression. [ 76 ]


During this period,  fertility  diminishes but is not considered to reach zero until the official date of menopause. The official date is determined retroactively, once 12 months have passed after the last appearance of menstrual blood.


The menopause transition typically begins between 40 and 50 years of age (average 47.5). [ 77 ] [ 78 ]  The duration of perimenopause may be for up to eight years. [ 78 ]  Women will often, but not always, start these transitions (perimenopause and menopause) about the same time as their mother did. [ 79 ]


Some research appears to show that  melatonin  supplementation in perimenopausal women can improve thyroid function and gonadotropin levels, as well as restoring fertility and menstruation and preventing depression associated with menopause. [ 80 ]


The term "postmenopausal" describes women who have not experienced any menstrual flow for a minimum of 12 months, assuming that they have a  uterus  and are not pregnant or  lactating . [ 54 ]  The reason for this delay in declaring postmenopause is that periods are usually erratic during menopause. Therefore, a reasonably long stretch of time is necessary to be sure that the cycling has ceased. At this point a woman is considered infertile; however, the possibility of becoming pregnant has usually been very low (but not quite zero) for a number of years before this point is reached. [ citation needed ]


In women with or without a uterus, menopause or postmenopause can also be identified by a blood test showing a very high  follicle-stimulating hormone  level, greater than 25 IU/L in a random blood draw; it rises as ovaries become inactive. [ 54 ]  FSH continues to rise, as its counterpart estradiol continues to drop for about 2 years after the last menstrual period, after which the levels of each of these hormones stabilize. The stabilization period after the begin of early postmenopause has been estimated to last 3 to 6 years, so early postmenopause lasts altogether about 5 to 8 years, during which hormone withdrawal effects such as hot flashes disappear. [ 54 ]  Finally, late postmenopause has been defined as the remainder of a woman s lifespan, when reproductive hormones do not change any more. [ citation needed ]


A period-like flow during postmenopause, even spotting, may be a sign of  endometrial cancer .


Perimenopause is a natural stage of life. It is not a disease or a disorder. Therefore, it does not automatically require any kind of medical treatment. However, in those cases where the physical, mental, and emotional effects of perimenopause are strong enough that they significantly disrupt the life of the woman experiencing them, palliative medical therapy may sometimes be appropriate.


In the context of the menopause,  menopausal hormone therapy  (MHT) is the use of  estrogen  in women without a uterus and estrogen plus  progestogen  in women who have an intact uterus. [ 81 ]


MHT may be reasonable for the treatment of menopausal symptoms, such as hot flashes. [ 82 ]  It is the most effective treatment option, especially when delivered as a skin patch. [ 83 ] [ 84 ]  Its use, however, appears to increase the risk of  strokes  and  blood clots . [ 85 ]  When used for menopausal symptoms the global recommendation is MHT should be prescribed for a long as there are defined treatment effects and goals for the individual woman. [ 20 ]


MHT is also effective for preventing bone loss and  osteoporotic  fracture, [ 86 ]  but it is generally recommended only for women at significant risk for whom other therapies are unsuitable. [ 87 ]


MHT may be unsuitable for some women, including those at increased risk of cardiovascular disease, increased risk of thromboembolic disease (such as those with obesity or a history of venous thrombosis) or increased risk of some types of cancer. [ 87 ]  There is some concern that this treatment increases the risk of breast cancer. [ 88 ]  Women at increased risk of cardiometabolic disease and VTE may be able to use transdermal estradiol which does not appear to increase risks in low to moderate doses. [ 20 ]


Adding  testosterone  to hormone therapy has a positive effect on sexual function in postmenopausal women, although it may be accompanied by hair growth or acne if used in excess. Transdermal testosterone therapy in appropriate dosing is generally safe. [ 89 ]


SERMs  are a category of drugs, either synthetically produced or derived from a botanical source, that act selectively as agonists or antagonists on the  estrogen receptors  throughout the body. The most commonly prescribed SERMs are  raloxifene  and  tamoxifen . Raloxifene exhibits oestrogen agonist activity on bone and lipids, and antagonist activity on breast and the endometrium. [ 90 ]  Tamoxifen is in widespread use for treatment of hormone sensitive breast cancer. Raloxifene prevents vertebral fractures in postmenopausal, osteoporotic women and reduces the risk of invasive breast cancer. [ 91 ]


Some of the  SSRIs  and  SNRIs  appear to provide some relief from vasomotor symptoms. [ 22 ] [ 21 ]  The most effective SSRIs and SNRIs are  paroxetine ,  escitalopram ,  citalopram ,  venlafaxine , and  desvenlafaxine . [ 21 ]  They may, however, be associated with appetite and sleeping problems, constipation and nausea. [ 22 ] [ 92 ]


Gabapentin  or  fezolinetant  can also improve the frequency and severity of vasomotor symptoms. [ 22 ] [ 21 ]  Side effects of using gabapentin include drowsiness and headaches. [ 22 ] [ 92 ]


Cognitive behavioural therapy  and  clinical hypnosis  can decrease the amount women are affected by hot flashes. [ 21 ]   Mindfulness  is not yet proven to be effective in easing vasomotor symptoms. [ 93 ] [ 94 ] [ 21 ]


Exercise has been thought to reduce postmenopausal symptoms through the increase of endorphin levels, which decrease as estrogen production decreases. [ 95 ]  However, there is insufficient evidence to suggest that exercise helps with the symptoms of menopause. [ 21 ]  Similarly, yoga has not been shown to be useful as a treatment for vasomotor symptoms. [ 21 ]


However a high  BMI  is a risk factor for vasomotor symptoms in particular. Weight loss may help with symptom management. [ 96 ] [ 21 ]


There is no strong evidence that cooling techniques such as using specific clothing or environment control tools (for example fans) help with symptoms. [ 21 ]  Paced breathing and  relaxation  are not effective in easing symptoms. [ 21 ]


There is no evidence of consistent benefit of taking any  dietary supplements  or  herbal products  for menopausal symptoms. [ 21 ] [ 97 ] [ 98 ]  These widely marketed but ineffective supplements include  soy isoflavones ,  pollen extracts ,  black cohosh ,  omega-3  among many others. [ 21 ] [ 99 ] [ 100 ]


There is no evidence of consistent benefit of  alternative therapies  for menopausal symptoms despite their popularity. [ 98 ] [ 21 ]


As of 2023, there is no evidence to support the efficacy of  acupuncture  as a management for menopausal symptoms. [ 21 ] [ 101 ] [ 98 ]  The  Cochrane review  found not enough evidence in 2016 to show a difference between Chinese herbal medicine and placebo for the  vasomotor  symptoms. [ 102 ]


The menopause transition is a process, involving hormonal, menstrual, and typically vasomotor changes. However, the experience of the menopause as a whole is very much influenced by psychological and social factors, such as past experience, lifestyle, social and cultural meanings of menopause, and a woman's social and material circumstances. Menopause has been described as a  biopsychosocial  experience, with social and cultural factors playing a prominent role in the way menopause is experienced and perceived. [ citation needed ]


The paradigm within which a woman considers menopause influences the way she views it: women who understand menopause as a medical condition rate it significantly more negatively than those who view it as a life transition or a symbol of aging. [ 105 ]  There is some evidence that negative attitudes and expectations, held before the menopause, predict symptom experience during the menopause, [ 106 ]  and beliefs and attitudes toward menopause tend to be more positive in postmenopausal than in premenopausal women. [ 107 ]   Women with more negative attitudes towards the menopause report more symptoms during this transition. [ 106 ]


Menopause is a stage of life experienced in different ways. It can be characterized by personal challenges, changes in personal roles within the family and society. Women's approaches to changes during menopause are influenced by their personal, family and sociocultural background. [ 108 ]  Women from different regions and countries also have different attitudes. Postmenopausal women had more positive attitudes toward menopause compared with peri- or premenopausal women. Other influencing factors of attitudes toward menopause include age, menopausal symptoms, psychological and socioeconomical status, and profession and ethnicity. [ 109 ]


Ethnicity and geography play roles in the experience of menopause. American women of different ethnicities report significantly different types of menopausal effects. One major study found Caucasian women most likely to report what are sometimes described as psychosomatic symptoms, while African-American women were more likely to report vasomotor symptoms. [ 110 ]


There may be variations in experiences of women from different ethnic backgrounds regarding menopause and care. Immigrant women reported more vasomotor symptoms and other physical symptoms and poorer mental health than non-immigrant women and were mostly dissatisfied with the care they had received. Self-management strategies for menopausal symptoms were also influenced by culture. [ 111 ]


Two multinational studies of Asian women, found that hot flushes were not the most commonly reported symptoms, instead body and joint aches, memory problems, sleeplessness, irritability and migraines were. [ 112 ]  In another study comparing experiences of menopause amongst White Australian women and women in Laos, Australian women reported higher rates of depression, as well as fears of aging, weight gain and cancer – fears not reported by Laotian women, who positioned menopause as a positive event. [ 113 ]   Japanese women  experience menopause effects, or  kōnenki  (更年期), in a different way from American women. [ 114 ]  Japanese women report lower rates of hot flashes and night sweats; this can be attributed to a variety of factors, both biological and social. Historically,  kōnenki  was associated with wealthy middle-class housewives in Japan, i.e., it was a "luxury disease" that women from traditional, inter-generational rural households did not report. Menopause in Japan was viewed as a symptom of the inevitable process of aging, rather than a "revolutionary transition", or a "deficiency disease" in need of management. [ 114 ]  As of 2005, in Japanese culture, reporting of vasomotor symptoms has been on the increase, with research finding that of 140 Japanese participants, hot flashes were prevalent in 22.1%. [ 115 ]  This was almost double that of 20 years prior. [ 116 ]  Whilst the exact cause for this is unknown, possible contributing factors include dietary changes, increased medicalisation of middle-aged women and increased media attention on the subject. [ 116 ]  However, reporting of vasomotor symptoms is still "significantly" lower than in North America. [ 117 ]


Additionally, while most women in the United States apparently have a negative view of menopause as a time of deterioration or decline, some studies seem to indicate that women from some Asian cultures have an understanding of menopause that focuses on a sense of liberation and celebrates the freedom from the risk of pregnancy. [ 118 ]  Diverging from these conclusions, one study appeared to show that many American women "experience this time as one of liberation and  self-actualization ". [ 119 ]


In some women, menopause may bring about a sense of loss related to the end of fertility. In addition, this change often aligns with other stressors, such as the responsibility of looking after elderly parents or dealing with the emotional challenges of " empty nest syndrome " when children move out of the family home. This situation can be accentuated in cultures where  being older is negatively perceived .


Midlife is typically a life stage when men and women may be dealing with demanding life events and responsibilities, such as work, health problems, and caring roles. For example, in 2018 in the UK women aged 45–54 report more work-related stress than men or women of any other age group. [ 120 ]  Hot flashes are often reported to be particularly distressing at work and lead to embarrassment and worry about potential  stigmatisation . [ 121 ]  A June 2023 study by the Mayo Clinic estimated an annual loss of $1.8 billion in the United States due to workdays missed as a result of menopause symptoms. [ 122 ]   This was one of the largest studies to date examining the impact of menopause symptoms on work outcomes. The research concluded there was a strong need to improve medical treatment for menopausal women and make the workplace environment more supportive to avoid such productivity losses.


Menopause literally means the "end of monthly cycles" (the end of  monthly periods  or  menstruation ), from the Greek word  pausis  ("pause") and  mēn  ("month"). This is a medical coinage; the Greek word for  menses  is actually different. In Ancient Greek, the menses were described in the plural,  ta emmēnia  ("the monthlies"), and its modern descendant has been clipped to  ta emmēna . The Modern Greek medical term is  emmenopausis  in  Katharevousa  or  emmenopausi  in  Demotic Greek . The Ancient Greeks did not produce medical concepts about any symptoms associated with end of menstruation and did not use a specific word to refer to this time of a woman's life. The word menopause was invented by French doctors at the beginning of the nineteenth century. Greek etymology was reconstructed at this time and it was the Parisian student doctor Charles-Pierre-Louis de Gardanne who invented a variation of the word in 1812, which was edited to its final French form in 1821. [ 123 ]


Some of them noted that peasant women had no complaints about the end of menses, while urban middle-class women had many troubling symptoms. Doctors at this time considered the symptoms to be the result of urban lifestyles of sedentary behaviour, alcohol consumption, too much time indoors, and over-eating, with a lack of fresh fruit and vegetables. [ 124 ]


The word "menopause" was coined specifically for female humans, where the end of fertility is traditionally indicated by the permanent stopping of monthly menstruations. However, menopause exists in some other animals, many of which do not have monthly menstruation; [ 125 ]  in this case, the term means a natural end to fertility that occurs before the end of the natural lifespan.


In the 21st century, celebrities have spoken out about their experiences of the menopause, which has led to it becoming less of a taboo as it has boosted awareness of the debilitating symptoms. Subsequently, TV shows have been running features on the menopause to help women experiencing symptoms. In the UK  Lorraine Kelly  has been an advocate for getting women to speak about their experiences including sharing her own. This has led to an increase in women seeking treatment such as HRT. [ 126 ]   Davina McCall  also led an awareness campaign based on a documentary on  Channel 4 . [ 127 ]


In the UK,  Carolyn Harris  sponsored the Menopause (Support and Services) Bill in June 2021. It was to exempt hormone replacement therapy from National Health Service  prescription charges  and to make provisions about menopause support and services, including public education and communication in supporting perimenopausal and post-menopausal women, and to raise awareness of menopause and its effects. The bill was withdrawn on 29 October 2021. [ 128 ]


In the US,  David McKinley , Republican from West Virginia introduced the Menopause Research Act in September 2022 for $100 million in 2023 and 2024, but it stalled. [ 129 ]


The majority of mammal species reach menopause when they cease the production of ovarian follicles, which contain eggs (oocytes), between one-third and two-thirds of their maximum possible lifespan. [ 130 ]  However, few live long enough in the wild to reach this point. Humans are joined by a limited number of other species in which females live substantially longer than their ability to reproduce. Examples of others include  cetaceans :  beluga whales , [ 131 ]   narwhals , [ 131 ]   orcas , [ 132 ]   false killer whales [ 133 ]  and  short-finned pilot whales . [ 134 ]


Menopause has been reported in a variety of other vertebrate species, but these examples tend to be from captive individuals, and thus are not necessarily representative of what happens in natural populations in the wild. Menopause in captivity has been observed in several species of nonhuman  primates , [ 125 ]  including  rhesus monkeys [ 135 ]  and  chimpanzees . [ 136 ]  Some research suggests that wild chimpanzees do not experience menopause, as their fertility declines are associated with declines in overall health. [ 137 ]  Menopause has been reported in elephants in captivity [ 138 ]  and  guppies . [ 139 ]  Dogs do not experience menopause; the  canine estrus cycle  simply becomes irregular and infrequent. Although older female dogs are not considered good candidates for breeding, offspring have been produced by older animals, see  Canine reproduction . Similar observations have been made in cats. [ 140 ]


Life histories  show a varying degree of  senescence ; rapid senescing organisms (e.g.,  Pacific salmon  and  annual plants ) do not have a post-reproductive life-stage. Gradual senescence is exhibited by all  placental mammalian  life histories. [ original research? ]


There are various theories on the origin and process of the  evolution of the menopause . These attempt to suggest evolutionary benefits to the human species stemming from the cessation of women's reproductive capability before the end of their natural lifespan. It is conjectured that in highly social groups  natural selection  favors females that stop reproducing and devote that post-reproductive life span to continuing to care for existing offspring, both their own and those of others to whom they are related, especially their granddaughters and grandsons. [ 141 ]


Atrophic vaginitis  is  inflammation of the vagina  as a result of  tissue thinning  due to low  estrogen  levels. [ 2 ]  Symptoms may include  pain during penetrative sex , vaginal itchiness or dryness, and an  urge to urinate  or  burning with urination . [ 1 ] [ 3 ]  It generally does not resolve without ongoing treatment. [ 1 ]  Complications may include  urinary tract infections . [ 1 ]  Atrophic vaginitis as well as  vulvovaginal atrophy, bladder and urethral dysfunctions are a group of conditions that constitute genitourinary syndrome of menopause (GSM). [ 4 ]  Diagnosis is typically based on symptoms. [ 1 ]


The decrease in estrogen typically occurs following  menopause . [ 1 ]  Other causes may include  breastfeeding  or using specific medications. [ 1 ]  Risk factors include  smoking . [ 2 ]


Treatment for atrophic vaginitis may involve the use of topical estrogen or other estrogen replacement. To treat the symptoms, patients may use lubricants, but it may not help long term as it does not affect the tissues. [ 5 ]


In a majority of postmenopausal women, there are risk factors that can contribute to atrophic vaginitis. Specifically, these risk factors are directly related to decreased estrogen levels and vaginal health. Some risk factors include


All of these factors impact estrogen levels and vaginal health, causing an increase in Atrophic vaginitis development.


Atrophic vaginitis may be caused by tissue thinning, loss of elasticity, and loss of vaginal fluids from low estrogen levels. [ 5 ]  Normally, estrogen helps the vagina shed old cells, which are then converted into lactic acid by good bacteria. [ 15 ]  This keeps the vagina's pH acidic and healthy. [ 15 ]  When estrogen levels drop, this process slows down, leading to thinner vaginal tissue, less moisture, and a less acidic environment. [ 15 ]  As a result, there's a higher risk of getting vaginal and urinary tract infections. [ 15 ]  Normal menopause and treatments such as chemotherapy or medications may result in loss of estrogen.


Those with or had a history of  breast cancer  may be at a higher risk of developing atrophic vaginitis due to chemotherapy and other endocrine treatments. [ 4 ]  Estrogen is crucial for women's sexual and urinary health. [ 16 ]  It supports the tissues in the lower vagina and urinary tracts to keep them thick, elastic, and moist and ensuring good blood flow. [ 16 ] [ 17 ]  Estrogen helps maintain a thick, glycogen-rich vaginal lining, which healthy bacteria use to produce lactic acid to keep the vaginal environment acidic, reducing infection risks. [ 16 ]  In premenopausal women, the main form of estrogen is called estradiol and fluctuates between 40 and 200 pg/mL, rising to 600 pg/mL during ovulation. [ 16 ]  Postmenopause, estrogen levels drop significantly tp 5-18 pg/mL, leading to gradual changes in the urogenital area. [ 16 ]  All tissue types such as connective, epithelial, muscular, blood vessels, and nerves are affected and become thinner and less effective, which increases risk of infections, inflammation, injuries, and sores. [ 16 ]  Blood flow and sensation can decrease, causing pain during sex and the pH level can rise due to decreased lactic acid production, which can allow harmful bacteria and fungi to grow and cause infections. [ 16 ]


Antiestrogen medications may also contribute to the development of atrophic vaginitis. These medications include  danazol ,  nafarelin , and  medroxyprogesterone . Additional risk factors include smokers, those who have not given birth naturally (through the vagina), and increased prolactin levels while lactation. [ 14 ]


After menopause the  vaginal epithelium  changes and becomes a few layers thick. [ 18 ]  Many of the signs and symptoms that accompany menopause occur in atrophic vaginitis. [ 3 ]  The earliest symptoms of atrophic vaginitis may be decreased vaginal lubrication, while other symptoms may appear later. [ 14 ]  Genitourinary symptoms include


It can be challenging to diagnose atrophic vaginitis given that the symptoms are mild and nonspecific for many postmenopausal women. [ 23 ]  Since women can have signs and symptoms that could be attributed to other causes, diagnosis is based upon the symptoms that cannot be better accounted for by another diagnosis. [ 19 ]


To determine if atrophic vaginitis is the cause for a patient's symptoms, differential diagnosis may be used. Other diagnosis include  bacterial vaginosis ,  trichomoniasis , candidiasis, and contact irritation from irritants such as soaps, pantyliners, or tight-fitting clothing. [ 14 ]  For example, a person who does not feel itching is unlikely to have candidiasis and no odor likely rules out bacterial vaginosis. [ 24 ]


Lab tests usually do not provide information that will aid in diagnosing. A visual exam is useful. The observations of the following may indicate lower estrogen levels: little pubic hair, loss of the labial fat pad, thinning and resorption of the  labia minora , and the narrowing of the vaginal opening. An internal exam will reveal the presence of low vaginal muscle tone, the lining of the vagina appears smooth, shiny, pale with loss of folds. The cervical fornices may have disappeared and the  cervix  can appear flush with the top of the  vagina . Inflammation is apparent when the vaginal lining bleeds easily and appears swollen. [ 1 ]


The vaginal  pH  will change from being acidic to a more neutral pH at around 4.5 or higher. This is typically taken by placing Litmus test strip on the wall of the vagina. [ 25 ]  Papillary and reticular, as well as skin and dermal tissue atrophy are observed via histological examinations. Observed reduced vascularization, atrophy of epithelial tissue leading to reduced thickness, and paleness are all apparent in post-menopausal women during histological examinations. [ 26 ]  Microscopy laboratory tests may be used to rule out symptoms caused by trichomoniasis and other bacteria. [ 14 ]  A  Papanicolaou test , also known as a pap test, would not be useful as it does not correlate strongly with the symptoms of atrophic vaginitis. [ 27 ]


The Vaginal Maturation Index (VMI) is a measure used to assess the composition of different types of cells in the vaginal lining. [ 28 ]  It helps to evaluate the hormonal environment in the vagina by calculating the proportion of different types of cells present in the vagina. [ 28 ]  During different life stages, such as before the first menstural cycle, during reproductive years, and after menopause, the distribution of these cell types changes. [ 28 ]  VMI is determined using a specific formula and provides a more comprehensive view of the hormonal effects on the vagina over time than a single hormone level measurement. [ 28 ]  VMI is particularly useful in clinical research for evaluating the impact of hormone therapy and changes in sexual function during menopause. [ 28 ]  VMI is also a better measure of vaginal atrophy than patient-reported symptoms of vaginal dryness. [ 28 ]


Symptoms of genitourinary syndrome of menopause (GSM) will unlikely be resolved without treatment. [ 1 ]  Some individuals may have many or a few symptoms so treatment is provided that best suits each person. If other health problems are also present, these can be taken into account when determining the best course of treatment. For those who have symptoms related to sexual activities, a lubricant may be sufficient. [ 1 ] [ 29 ]  If both urinary and genital symptoms exist, local, low-dose estrogen therapy can be effective. Those individuals who are survivors of hormone-sensitive cancer may need to be treated more cautiously. [ 1 ]  Some people can have symptoms that are widespread and may be at risk for osteoporosis. Estrogen and adjuvants may be best. [ 29 ]  Recent research showed a medication called ospemifene can be an alternative oral treatment if vaginal products or hormone therapy is not suitable for patients surviving gynecological cancer. [ 30 ]  Ospemifene can increase collagen production to improve vaginal tissue, which will help reduce GSM symptoms. [ 30 ]  Studies have shown this medication has helped increase vaginal pH, elasticity, and moisture to improve vaginal health as well as sexual and emotional well-being. [ 30 ]