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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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In the Western world, the typical age of menopause (last period from natural causes) is between 40 and 61 and the average age for last period is 51 years. The average age of natural menopause in Australia is 51.7 years. In India and the Philippines, the median age of natural menopause is considerably earlier, at 44 years.
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 and affects 1 to 2% of women by age 40.
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.
Women who have undergone hysterectomy with ovary conservation go through menopause on average 3.7 years earlier than the expected age. Other factors that can promote an earlier onset of menopause (usually 1 to 3 years early) are smoking cigarettes or being extremely thin.
Breastfeeding is a common cause of secondary amenorrhoea, and often the condition lasts for over six months. Breastfeeding typically lasts longer than lactational amenorrhoea, and the duration of amenorrhoea varies depending on how often a women breastfeeds. Lactational amenorrhoea has been advocated as a method of family planning, especially in developing countries where access to other methods of contraception may be limited. Breastfeeding is said to prevent more births in the developing world than any other method of birth control or contraception. Lactational amenorrhoea is 98% percent effective as a method of preventing pregnancy in the first six months postpartum.
Menopause confers:
- A possible but contentious increased risk of atherosclerosis. The risk of acute myocardial infarction and other cardiovascular diseases rises sharply after menopause, but the risk can be reduced by managing risk factors, such as tobacco smoking, hypertension, increased blood lipids and body weight.
- Increased risk of osteopenia, osteoporosis, and accelerated lung function decline.
Women who experience menopause before 45 years of age have an increased risk of heart disease, death, and impaired lung function.
Certain medications, particularly contraceptive medications, can induce amenorrhoea in a healthy woman. The lack of menstruation usually begins shortly after beginning the medication and can take up to a year to resume after stopping a medication. Hormonal contraceptives that contain only progestogen like the oral contraceptive Micronor, and especially higher-dose formulations like the injectable Depo Provera commonly induce this side-effect. Extended cycle use of combined hormonal contraceptives also allow suppression of menstruation. Patients who use and then cease using contraceptives like the combined oral contraceptive pill may experience secondary amenorrhoea as a withdrawal symptom. The link is not well understood, as studies have found no difference in hormone levels between women who develop amenorrhoea as a withdrawal symptom following the cessation of OCOP use and women who experience secondary amenorrhoea because of other reasons. New contraceptive pills, like continuous oral contraceptive pills (OCPs) which do not have the normal 7 days of placebo pills in each cycle, have been shown to increase rates of amenorrhoea in women. Studies show that women are most likely to experience amenorrhoea after 1 year of treatment with continuous OCP use.
The use of opiates (such as heroin) on a regular basis has also been known to cause amenorrhoea in longer term users.
Anti-psychotic drugs used to treat schizophrenia have been known to cause amenorrhoea as well. New research suggests that adding a dosage of Metformin to an anti-psychotic drug regimen can restore menstruation. Metformin decreases resistance to the hormone insulin, as well as levels of prolactin, testosterone, and lutenizing hormone (LH). Metformin also decreases the LH/FSH ratio. Results of the study on Metformin further implicate the regulation of these hormones as a main cause of secondary amenorrhoea.
For most women, alteration of menstrual periods is the principal indication of chronic anovulation. Ovulatory menstrual periods tend to be regular and predictable in terms of cycle length, duration and heaviness of bleeding, and other symptoms. Ovulatory periods are often accompanied by midcycle symptoms such as mittelschmerz or premenstrual symptoms. In contrast, anovulation usually manifests itself as irregularity of menstrual periods, that is, unpredictable variability of intervals, duration, or bleeding. Anovulation can also cause cessation of periods (secondary amenorrhea) or excessive bleeding (dysfunctional uterine bleeding). Mittelschmerz and premenstrual symptoms tend to be absent or reduced when a woman is anovulatory.
This accounts for around 10-15% of all cases of anovulation. The ovaries can stop working in about 5% of cases. This may be because the ovaries do not contain eggs. However, a complete blockage of the ovaries is rarely a cause of infertility. Blocked ovaries can start functioning again without a clear medical explanation. In some cases, the egg may have matured properly, but the follicle may have failed to burst (or the follicle may have burst without releasing the egg). This is called luteinised unruptured follicle syndrome (LUFS). Physical damage to the ovaries, or ovaries with multiple cysts, may affect their ability to function. This is called ovarian . Patients who are suffering from Stein-Leventhal syndrome (also referred to as polycystic ovary syndrome, or PCOS) can also suffer from anovulation. Up to 90% of cases of anovulation are caused by PCOS; this syndrome is usually hereditary.
Weight loss or anorexia can also cause hormonal imbalance, leading to irregular ovulation (dysovulation). It is possible that this mechanism evolved to protect the mother’s health. A pregnancy where the mother is weak could pose a risk to the baby’s and mother’s health. On the other hand, excess weight can also create ovarian dysfunctions. Dr Barbieri of Harvard Medical School has indicated that cases of anovulation are quite frequent in women with a BMI (body mass index) over 27 /. Unfortunately, not only does excess weight have a negative impact on ovulation itself, but also on treatment efficacy and outcomes of ART (assisted reproductive technique).
A study of a population of French women from 1670 and 1789 shows that those who married at age 20–24 had 7.0 children on average and 3.7% remained childless. Women who married at age 25–29 years had a mean of 5.7 children and 5.0% remained childless. Women who married at 30–34 years had a mean of 4.0 children and 8.2% remained childless. The average age at last birth in natural fertility populations that have been studied is around 40.
In 1957, a study was done on a large population (American Hutterites) that never used birth control. The investigators measured the relationship between the age of the female partner and fertility. (Infertility rates today are believed to be higher in the general population than for the population in this study from the 1950s.)
This 1957 study found that:
- By age 30, 7% of couples were infertile
- By age 35, 11% of couples were infertile
- By age 40, 33% of couples were infertile
- At age 45, 87% of couples were infertile
Oligomenorrhea can be a result of prolactinomas (adenomas of the anterior pituitary). It may be caused by thyrotoxicosis, hormonal changes in perimenopause, Prader–Willi syndrome, and Graves disease.
"Endurance exercises such as running or swimming can affect the reproductive physiology of women athletes. Female runners, swimmers and ballet dancers menstruate infrequently in comparison to nonatheletic women of comparable age or not at all (amenorrhea). The degree of menstrual abnormality is directly proportional to the intensity of the exercise. For example, Malina et al., (1978) have shown menstrual irregularity is more common, and more severe among tennis players than among golfers" (modified by a student paper written by A. Lord)
Breastfeeding has been linked to irregularity of menstrual cycles due to hormones that delay ovulation.
Women with polycystic ovary syndrome (PCOS) are also likely to suffer from oligomenorrhea. PCOS is a condition in which excessive androgens (male sex hormones) are released by the ovaries. Women with PCOS show menstrual irregularities that range from oligomenorrhea and amenorrhea, to very heavy, irregular periods. The condition affects about 6% of premenopausal women.
Eating disorders can result in oligomenorrhea. Although menstrual disorders are most strongly associated with Anorexia nervosa, Bulimia nervosa may also result in oligomenorrhea or amenorrhea. There is some controversy regarding the mechanism for the menstrual dysregulation, since amenorrhea may sometimes precede substantial weight loss in some anorexics. Some researchers hypothesize that some as-yet unrecognized neuroendocrine phenomenon may be involved; the menstrual irregularities may be related to the biological undergirding of the disorders, rather than a result of nutritional deficiencies.
A menstrual disorder is an abnormal condition in a woman's menstrual cycle.
The cause is not entirely clear. Risk factors include having a family history of the condition.
Dysmenorrhea (or dysmenorrhoea), cramps or painful menstruation, involves menstrual periods that are accompanied by either sharp, intermittent pain or dull, aching pain, usually in the pelvis or lower abdomen.
Some factors associated with endometriosis include:
- not having had yet given birth
- prolonged exposure to estrogen - for example, in late menopause or early menarche
- obstruction of menstrual outflow - for example, in Müllerian anomalies
Several studies have investigated the potential link between exposure to dioxins and endometriosis, but the evidence is equivocal and potential mechanisms are poorly understood. A 2004 review of studies of dioxin and endometriosis concluded that "the human data supporting the dioxin-endometriosis association are scanty and conflicting", and a 2009 follow-up review also found that there was "insufficient evidence" in support of a link between dioxin exposure and women developing endometriosis. A 2008 review concluded that more work was needed, stating that "although preliminary work suggests a potential involvement of exposure to dioxins in the pathogenesis of endometriosis, much work remains to clearly define cause and effect and to understand the potential mechanism of toxicity".
Dysmenorrhea is estimated to affect approximately 25% of women. Reports of dysmenorrhea are greatest among individuals in their late teens and 20s, with reports usually declining with age. The prevalence in adolescent females has been reported to be 67.2% by one study and 90% by another. It has been stated that there is no significant difference in prevalence or incidence between races. Yet, a study of Hispanic adolescent females indicated a high prevalence and impact in this group. Another study indicated that dysmenorrhea was present in 36.4% of participants, and was significantly associated with lower age and lower parity. Childbearing is said to relieve dysmenorrhea, but this does not always occur. One study indicated that in nulliparous women with primary dysmenorrhea, the severity of menstrual pain decreased significantly after age 40. A questionnaire concluded that menstrual problems, including dysmenorrhea, were more common in females who had been sexually abused.
A survey in Norway showed that 14 percent of females between the ages of 20 to 35 experience symptoms so severe that they stay home from school or work. Among adolescent girls, dysmenorrhea is the leading cause of recurrent short-term school absence.
The prevalence of PCOS depends on the choice of diagnostic criteria. The World Health Organization estimates that it affects 116 million women worldwide as of 2010 (3.4% of women). One community-based prevalence study using the Rotterdam criteria found that about 18% of women had PCOS, and that 70% of them were previously undiagnosed.
Ultrasonographic findings of polycystic ovaries are found in 8–25% of normal women. 14% women on oral contraceptives are found to have polycystic ovaries. Ovarian cysts are also a common side effect of intrauterine devices (IUDs).
The inverse correlation between age and female fertility in later reproductive life is argued to motivate family planning well before having reached 35 years of age. Mapping of a woman's ovarian reserve, follicular dynamics and associated biomarkers can give an individual prognosis about future chances of pregnancy, facilitating an informed choice of when to have children. Notably, a higher level of anti-Müllerian hormone when tested in women in the general population has been found to have a positive correlation with natural fertility in women aged 30–44 aiming to conceive spontaneously, even after adjusting for age. Thus, AMH measurement is helpful to determine which women may need to conceive at an earlier age, and which women can potentially wait.
Irregular menstruation is a menstrual disorder whose manifestations include irregular cycle lengths as well as metrorrhagia (vaginal bleeding between expected periods).
Oligomenorrhea (or oligomenorrhoea) is infrequent (or, in occasional usage, very light) menstruation. More strictly, it is menstrual periods occurring at intervals of greater than 35 days, with only four to nine periods in a year. Menstrual periods should have been regularly established before the development of infrequent flow. The duration of such events may vary.
10% of cases occur in women who are ovulating, but progesterone secretion is prolonged because estrogen levels are low. This causes irregular shedding of the uterine lining and break-through bleeding. Some evidence has associated Ovulatory DUB with more fragile blood vessels in the uterus.
It may represent a possible endocrine dysfunction, resulting in menorrhagia or metrorrhagia.
Mid-cycle bleeding may indicate a transient estrogen decline, while late-cycle bleeding may indicate progesterone deficiency.
A diagnosis of PCOS suggests an increased risk of the following:
- Endometrial hyperplasia and endometrial cancer (cancer of the uterine lining) are possible, due to overaccumulation of uterine lining, and also lack of progesterone resulting in prolonged stimulation of uterine cells by estrogen. It is not clear whether this risk is directly due to the syndrome or from the associated obesity, hyperinsulinemia, and hyperandrogenism.
- Insulin resistance/Type II diabetes. A review published in 2010 concluded that women with PCOS have an elevated prevalence of insulin resistance and type II diabetes, even when controlling for body mass index (BMI). PCOS also makes a woman, particularly if obese, prone to gestational diabetes.
- High blood pressure, in particular if obese or during pregnancy
- Depression and anxiety
- Dyslipidemia – disorders of lipid metabolism — cholesterol and triglycerides. Women with PCOS show a decreased removal of atherosclerosis-inducing remnants, seemingly independent of insulin resistance/Type II diabetes.
- Cardiovascular disease, with a meta-analysis estimating a 2-fold risk of arterial disease for women with PCOS relative to women without PCOS, independent of BMI.
- Strokes
- Weight gain
- Miscarriage
- Sleep apnea, particularly if obesity is present
- Non-alcoholic fatty liver disease, again particularly if obesity is present
- Acanthosis nigricans (patches of darkened skin under the arms, in the groin area, on the back of the neck)
- Autoimmune thyroiditis
Early diagnosis and treatment may reduce the risk of some of these, such as type 2 diabetes and heart disease.
The risk of ovarian cancer and breast cancer is not significantly increased overall.
Irregular cycles or irregular periods is an abnormal variation in length of menstrual cycles. A female usually experiences cycle length variations of up to eight days between the shortest and longest cycle lengths. Lengths ranging between eight and 20 days are considered moderately irregular. Variation of 21 days or more is considered very irregular.
Alternatively, a single menstruation period may be defined as irregular if it is shorter than 21 days or longer than 36 days. If they are regularly shorter than 21 days or longer than 36 (or 35) days, the condition is termed polymenorrhea or oligomenorrhea, respectively.
Dysmenorrhea can be classified as either primary or secondary based on the absence or presence of an underlying cause. Secondary dysmenorrhea is dysmenorrhea which is associated with an existing condition.
The most common cause of secondary dysmenorrhea is endometriosis, which can be visually confirmed by laparoscopy in approximately 70% of adolescents with dysmenorrhea.
Other causes of secondary dysmenorrhea include leiomyoma, adenomyosis, ovarian cysts, and pelvic congestion.
Unequal leg length might hypothetically be one of the contributors, as it may contribute to a tilted pelvis, which may cause lower back pain, which in turn may be mistaken for menstrual pain, as women with lower back pain experience increased pain during their periods.
Other skeletal abnormalities, such as scoliosis (sometimes caused by spina bifida) might be possible contributors as well.
Menorrhagia is a menstrual period with excessively heavy flow and falls under the larger category of abnormal uterine bleeding (AUB).
Abnormal uterine bleeding can be caused by structural abnormalities in the reproductive tract, anovulation, bleeding disorders, hormone issues (such as hypothyroidism) or cancer of the reproductive tract. Initial evaluation aims at figuring out pregnancy status, menopausal status, and the source of bleeding.
Treatment depends on the cause, severity, and interference with quality of life. Initial treatment often involve contraceptive pills. Surgery can be an effective second line treatment for those women whose symptoms are not well-controlled. Approximately 53 in 1000 women are affected by AUB.
Excessive menstruation between puberty and 19 years of age is called puberty menorrhagia. Excessive menstruation is defined as bleeding over 80 ml per menstrual period or lasting more than 7 days. The most common cause for puberty menorrhagia is dysfunctional uterine bleeding. The other reasons are idiopathic thrombocytopenic purpura, hypothyroidism, genital tuberculosis, polycystic ovarian disease, leukemia and coagulation disorders. The most common physiological reason for puberty menorrhagia is the immaturity of hypothalamic-pituitary-ovarian axis, leading to inadequate positive feedback and sustained high estrogen levels. Most patients present with anemia due to excessive blood loss.
The patient is assessed with a thorough medical history, physical examination (to look for features of anemia), gynaecological examination (to rule out local causes) and laboratory investigations (to rule out coagulopathies and malignancy). It is mandatory to exclude pregnancy. The treatment is determined based on the cause of menorrhagia. In case of puberty menorrhagia due to immaturity of hypothalamic axis, hormonal therapy is beneficial. Treatment for blood loss should be done simultaneously with iron therapy in mild to moderate blood loss and blood transfusion in severe blood loss.
The risk of pregnancy complications increases as the mother's age increases. Risks associated with childbearing over the age of 50 include an increased incidence of gestational diabetes, hypertension, delivery by caesarean section, miscarriage, preeclampsia, and placenta previa. In comparison to mothers between 20 and 29 years of age, mothers over 50 are at almost three times the risk of low birth weight, premature birth, and extremely premature birth; their risk of extremely low birth weight, small size for gestational age, and fetal mortality was almost double.
Where an underlying cause can be identified, treatment may be directed at this. Clearly heavy periods at menarche and menopause may settle spontaneously (the menarche being the start and menopause being the cessation of periods).
If the degree of bleeding is mild, all that may be sought by the woman is the reassurance that there is no sinister underlying cause. If anemia occurs due to bleeding then iron tablets may be used to help restore normal hemoglobin levels.
The condition is often treated with hormones, particularly as abnormal uterine bleeding commonly occurs in the early and late menstrual years when contraception is also sought. Usually, oral combined contraceptive or progesterone only pills may be taken for a few months, but for longer-term treatment the alternatives of injected Depo Provera or the more recent progesterone releasing IntraUterine System (IUS) may be used. Fibroids may respond to hormonal treatment, and if they do not, then surgical removal may be required.
Tranexamic acid tablets that may also reduce loss by up to 50%. This may be combined with hormonal medication previously mentioned.
Anti-inflammatory medication like NSAIDs may also be used. NSAIDs are the first-line medications in ovulatory menorrhagia, resulting in an average reduction of 20-46% in menstrual blood flow. For this purpose, NSAIDs are ingested for only 5 days of the menstrual cycle, limiting their most common adverse effect of dyspepsia.
A definitive treatment for menorrhagia is to perform hysterectomy (removal of the uterus). The risks of the procedure have been reduced with measures to reduce the risk of deep vein thrombosis after surgery, and the switch from the front abdominal to vaginal approach greatly minimizing the discomfort and recuperation time for the patient; however extensive fibroids may make the womb too large for removal by the vaginal approach. Small fibroids may be dealt with by local removal (myomectomy). A further surgical technique is endometrial ablation (destruction) by the use of applied heat (thermoablation).
In the UK the use of hysterectomy for menorrhagia has been almost halved between 1989 and 2003. This has a number of causes: better medical management, endometrial ablation and particularly the introduction of IUS which may be inserted in the community and avoid the need for specialist referral; in one study up to 64% of women cancelled surgery.