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During the transition to menopause, menstrual patterns can show shorter cycling (by 2–7 days); longer cycles remain possible. There may be irregular bleeding (lighter, heavier, spotting). 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.
In post-menopausal women, however, any genital bleeding is an alarming symptom that requires an appropriate study to rule out the possibility of malignant diseases.
Symptoms that may appear during menopause and continue through postmenopause include:
- painful intercourse
- vaginal dryness
- atrophic vaginitis – thinning of the membranes of the vulva, the vagina, the cervix, and the outer urinary tract, along with considerable shrinking and loss in elasticity of all of the outer and inner genital areas.
Symptoms are set into 3 categories: mild, moderate, and severe. Mild symptoms include abdominal bloating and feeling of fullness, nausea, diarrhea, and slight weight gain. Moderate symptoms include excessive weight gain (weight gain of greater than 2 pounds per day), increased abdominal girth, vomiting, diarrhea, darker urine, decreased urine output, excessive thirst, and skin and/or hair feeling dry (in addition to mild symptoms). Severe symptoms are fullness/bloating above the waist, shortness of breath, pleural effusion, urination significantly darker or has ceased, calf and chest pains, marked abdominal bloating or distention, and lower abdominal pains (in addition to mild and moderate symptoms).
OHSS is divided into the categories mild, moderate, severe, and critical.
In mild forms of OHSS the ovaries are enlarged (5–12 cm) and there may be additional accumulation of ascites with mild abdominal distension, abdominal pain, nausea, and diarrhea. In severe forms of OHSS there may be hemoconcentration, thrombosis, distension, oliguria (decreased urine production), pleural effusion, and respiratory distress. Early OHSS develops before pregnancy testing and late OHSS is seen in early pregnancy.
Criteria for severe OHSS include enlarged ovary, ascites, hematocrit > 45%, WBC > 15,000, oliguria, creatinine 1.0-1.5 mg/dl, creatinine clearance > 50 ml/min, liver dysfunction, and anasarca. Critical OHSS includes enlarged ovary, tense ascites with hydrothorax and pericardial effusion, hematocrit > 55%, WBC > 25,000, oligoanuria, creatinine > 1.6 mg/dl, creatinine clearance < 50 ml/min, renal failure, thromboembolic phenomena, and ARDS.
On average, the ovaries supply a woman with eggs until age 51, the average age of natural menopause.
POF is not the same as a natural menopause, in that the dysfunction of the ovaries, loss of eggs, or removal of the ovaries at a young age is not a normal physiological occurrence.
Infertility is the result of this condition, and is the most discussed problem resulting from it, but there are additional health implications of the problem, and studies are ongoing. For example, osteoporosis or decreased bone density affects almost all women with POF due to an insufficiency of estrogen. There is also an increased risk of heart disease, hypothyroidism in the form of Hashimoto's thyroiditis, Addison's disease, and other auto-immune disorders.
Hormonally, POF is defined by abnormally low levels of estrogen and high levels of FSH, which demonstrate that the ovaries are no longer responding to circulating FSH by producing estrogen and developing fertile eggs. The ovaries will likely appear shriveled.
The age of onset can be as early as the teenage years, or can even exist from birth, but varies widely. If a girl never begins menstruation, it is called primary ovarian failure. The age of 40 was chosen as the cut-off point for a diagnosis of POF. This age was chosen somewhat arbitrarily, as all women's ovaries decline in function over time. However an age needed to be chosen to distinguish usual menopause from the abnormal state of premature menopause. Premature ovarian failure has components to it that distinguish it from normal menopause.
By the age of 40, approximately one percent of women have POF. Women suffering from POF usually experience menopausal symptoms that are more severe than the symptoms found in older menopausal women.
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.
The date of the final menstrual period is usually taken as the point when menopause has occurred. During the menopausal transition and after menopause, women can experience a wide range of symptoms.
The most common words women use to describe how they felt in the 2 hours after being given the diagnosis of primary ovarian insufficiency are "devastated, "shocked," and "confused." These are words that describe emotional trauma. The diagnosis is more than infertility and affects a woman’s physical and emotional well-being. Patients face the acute shock of the diagnosis, associated stigma of infertility, grief from the death of dreams, anxiety and depression from the disruption of life plans, confusion around the cause, symptoms of estrogen deficiency, worry over the associated potential medical sequelae such as reduced bone density and cardiovascular risk, and the uncertain future that all of these factors create. There is a need for an evidence-based integrative medicine program to assist women with primary ovarian insufficiency. Presently such a program does not exist in the community, but a community of practice has formed to address this deficiency. Women with primary ovarian insufficiency perceive lower social support than control women, so building a trusted community of practice for them would be expected to improve their well being. It is important to connect women with primary ovarian insufficiency to an appropriate collaborative care team because the condition has been clearly associated with suicide related to the stigma of infertility. Suicide rates are known to be increased in women who experience infertility.
Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulation is a common cause of infertility.
In addition to the alteration of menstrual periods and infertility, chronic anovulation can cause or exacerbate other long term problems, such as hyperandrogenism or osteopenia. It plays a central role in the multiple imbalances and dysfunctions of polycystic ovary syndrome.
During the first two years after menarche 50% of the menstrual cycles could be anovulatories.
It is in fact possible to restore ovulation using appropriate medication, and ovulation is successfully restored in approximately 90% of cases. The first step is the diagnosis of anovulation. The identification of anovulation is not easy; contrary to what is commonly believed, women undergoing anovulation still have (more or less) regular periods. In general, patients only notice that there is a problem once they have started trying to conceive.
Temperature charting is a useful way of providing early clues about anovulation, and can help gynaecologists in their diagnosis.
Poor ovarian reserve is a condition of low fertility characterized by 1): low numbers of remaining oocytes in the ovaries or 2) possibly impaired preantral oocyte development or recruitment. Recent research suggests that premature ovarian aging and premature ovarian failure (aka primary ovarian insufficiency) may represent a continuum of premature ovarian senescence. It is usually accompanied by high FSH (follicle stimulating hormone) levels.
Quality of the eggs (oocytes) may also be impaired as a 1989 study by Scott et al. of 758 in vitro fertilisation (IVF) cycles showed a dramatic decline in implantation rates between high (> 25 mIU/mL) and low day three FSH (<15 mIU/mL) women even though the ages of the women were equivalent between the two groups (mean age 35 years). However, other studies show no association with elevated FSH levels and genetic quality of embryos after adjusting for age. The decline in quality was age related, not FSH related as the younger women with high day three FSH levels had higher live birth rates than the older women with high FSH. There was no significant difference in genetic embryo quality between same aged women regardless of FSH levels. A 2008 study concluded that diminished reserve did not affect the quality of oocytes and any reduction in quality in diminished reserve women was age related. One expert concluded: in young women with poor reserve when eggs are obtained they have near normal rates of implantation and pregnancy rates, but they are at high risk for IVF cancellation; if eggs are obtained, pregnancy rates are typically better than in older woman with normal reserve. However, if the FSH level is extremely elevated these conclusions are likely not applicable.
Anovulation is usually associated with specific symptoms. However, it is important to note that they are not necessarily all displayed simultaneously. Amenorrhea (absence of menstruation) occurs in about 20% of women with ovulatory dysfunction. Infrequent and light menstruation occurs in about 40% of women with ovulatory dysfunction. Another potential symptom is irregular menstruation, where five or more menstrual cycles a year are five or more days shorter or longer than the length of the average cycle. Absence of mastodynia (breast pain or tenderness) occurs in about 20% of women with ovulatory problems. Also possible is increased body mass and facial hair, which is relatively easy to treat, and is often associated with PCOS, or polycystic ovary syndrome.
There is some controversy as the accuracy of the tests used to predict poor ovarian reserve. One systematic review concluded that the accuracy of predicting the occurrence of pregnancy is very limited. When a high threshold is used, to prevent couples from wrongly being refused IVF, only approximately 3% of IVF-indicated cases are identified as having unfavourable prospects in an IVF treatment cycle. Also, the review concluded the use of any ORT (Ovarian Reserve Testing) for outcome prediction cannot be supported. Also Centers for Disease Control and Prevention statistics show that the success rates for IVF with diminished ovarian reserve vary widely between IVF centers.
Unexplained infertility is infertility that is idiopathic in the sense that its cause remains unknown even after an infertility work-up, usually including semen analysis in the man and assessment of ovulation and fallopian tubes in the woman.
Female fertility is affected by age. Age is thus a major fertility factor for women. Menarche, the first menstrual period, usually occurs around 12-13, although it may happen earlier or later, depending on each girl. After puberty, female fertility increases and then decreases, with advanced maternal age causing an increased risk of female infertility. In humans, a woman's fertility peaks in the early and mid-20s, after which it starts to decline slowly. While many sources suggest a more dramatic drop at around 35, this is unclear since studies are still cited from the nineteenth century and earlier. One 2004 study of European women found fertility of the 27-34 and the 35–39 groups had only a four-percent difference. At age 45, a woman starting to try to conceive will have no live birth in 50–80 percent of cases. Menopause, or the cessation of menstrual periods, generally occurs in the 40s and 50s and marks the cessation of fertility, although age-related infertility can occur before then. The relationship between age and female fertility is sometimes referred to as a woman's "biological clock."
Common signs and symptoms of PCOS include the following:
- Menstrual disorders: PCOS mostly produces oligomenorrhea (fewer than nine menstrual periods in a year) or amenorrhea (no menstrual periods for three or more consecutive months), but other types of menstrual disorders may also occur.
- Infertility: This generally results directly from chronic anovulation (lack of ovulation).
- High levels of masculinizing hormones: Known as hyperandrogenism, the most common signs are acne and hirsutism (male pattern of hair growth, such as on the chin or chest), but it may produce hypermenorrhea (heavy and prolonged menstrual periods), androgenic alopecia (increased hair thinning or diffuse hair loss), or other symptoms. Approximately three-quarters of women with PCOS (by the diagnostic criteria of NIH/NICHD 1990) have evidence of hyperandrogenemia.
- Metabolic syndrome: This appears as a tendency towards central obesity and other symptoms associated with insulin resistance. Serum insulin, insulin resistance, and homocysteine levels are higher in women with PCOS.
Asians affected by PCOS are less likely to develop hirsutism than those of other ethnic backgrounds.
In the US, up to 25% of infertile couples have unexplained infertility.
Polycystic ovary syndrome (PCOS) is a set of symptoms due to elevated androgens (male hormones) in women. Signs and symptoms of PCOS include irregular or no menstrual periods, heavy periods, excess body and facial hair, acne, pelvic pain, difficulty getting pregnant, and patches of thick, darker, velvety skin. Associated conditions include type 2 diabetes, obesity, obstructive sleep apnea, heart disease, mood disorders, and endometrial cancer.
PCOS is due to a combination of genetic and environmental factors. Risk factors include obesity, not enough physical exercise, and a family history of someone with the condition. Diagnosis is based on two of the following three findings: no ovulation, high androgen levels, and ovarian cysts. Cysts may be detectable by ultrasound. Other conditions that produce similar symptoms include adrenal hyperplasia, hypothyroidism, and hyperprolactinemia.
PCOS has no cure. Treatment may involve lifestyle changes such as weight loss and exercise. Birth control pills may help with improving the regularity of periods, excess hair growth, and acne. Metformin and anti-androgens may also help. Other typical acne treatments and hair removal techniques may be used. Efforts to improve fertility include weight loss, clomiphene, or metformin. In vitro fertilization is used by some in whom other measures are not effective.
PCOS is the most common endocrine disorder among women between the ages of 18 and 44. It affects approximately 2% to 20% of this age group depending on how it is defined. It is one of the leading causes of poor fertility. The earliest known description of what is now recognized as PCOS dates from 1721 in Italy.
Female infertility refers to infertility in female humans. It affects an estimated 48 million women with the highest prevalence of infertility affecting people in South Asia, Sub-Saharan Africa, North Africa/Middle East, and Central/Eastern Europe and Central Asia. Infertility is caused by many sources, including nutrition, diseases, and other malformations of the uterus. Infertility affects women from around the world, and the cultural and social stigma surrounding it varies.
Hyperandrogenism, especially high levels of testosterone, can cause serious adverse effects on women’s bodies if left untreated. High testosterone levels have been seen to be associated with obesity, hypertension, amenorrhea(stop of menstrual cycles), and ovulatory dysfunction, which can lead to infertility. The more prominent signs of hyperandrogenism are hirsutism (unwanted growth of hair especially in the abdominal region and places on the back), acne after adolescence, deepening of voice, and alopecia(balding). Hyperandrogenism has also been seen to cause individuals to have a high tolerance to insulin, which can lead to type two diabetes, and dyslipidemia, such as high cholesterol. These effects have also been seen to have a large psychological impact on the individual, sometimes often leading to societal anxiety and depression, especially in adolescent girls and young women. Paired with obesity and hirsutism, it can cause the individual to have low self-esteem, and a poor view of oneself.
Hyperandrogenism affects 5-10% of females of reproductive age. Hyperandrogenism can affect both males and females, but is more noticeable in females due to the fact that elevated levels of androgens in females often facilitates virilization. Due to the fact that hyperandrogenism is characterized by the elevation of male sex hormone levels, symptoms of hyperandrogenism in men are often negligible. Hyperandrogenism in females is typically diagnosed in late adolescence with a medical evaluation. The medical evaluation tends to consist of a pelvic exam, observation of external symptoms, and a blood test measuring androgen levels.
There is no unanimous definition of female infertility, because the definition depends on social and physical characteristics which may vary by culture and situation. NICE guidelines state that: "A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner." It is recommended that a consultation with a fertility specialist should be made earlier if the woman is aged 36 years or over, or there is a known clinical cause of infertility or a history of predisposing factors for infertility. According to the World Health Organization (WHO), infertility can be described as the inability to become pregnant, maintain a pregnancy, or carry a pregnancy to live birth.
A clinical definition of infertility by the WHO and ICMART is “a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.” Infertility can further be broken down into primary and secondary infertility. Primary infertility refers to the inability to give birth either because of not being able to become pregnant, or carry a child to live birth, which may include miscarriage or a stillborn child.
Ovarian diseases can be classified as endocrine disorders or as a disorders of the reproductive system.
If the egg fails to release from the follicle in the ovary an ovarian cyst may form. Small ovarian cysts are common in healthy women. Some women have more follicles than usual (polycystic ovary syndrome), which inhibits the follicles to grow normally and this will cause cycle irregularities.
Other conditions include:
- Ovarian cancer
- Luteoma
- Hypogonadism
- Hyperthecosis
FSH insensitivity presents itself in females as two clusters of symptoms: 1) hypergonadotropic hypogonadism or hypoestrogenism, resulting in a delayed, reduced, or fully absent puberty and associated sexual infantilism (if left untreated), reduced uterine volume, and osteoporosis; and 2) ovarian dysgenesis or failure, resulting in primary or secondary amenorrhea, infertility, and normal sized to slightly enlarged ovaries. Males on the other hand are significantly less affected, presenting merely with partial or complete infertility, reduced testicular volume, and oligozoospermia (reduced spermatogenesis).
Hyperthecosis (or ovarian hyperthecosis) is hyperplasia of the theca interna of the ovary. Hyperthecosis occurs when an area of luteinization occurs along with stromal hyperplasia. The luteinized cells produce androgens, which may lead to hirsutism and virilization (or masculinization) in affected women.
The term hyperthecosis refers to the presence of nests of luteinized theca cells in the ovarian stroma due to differentiation of the ovarian interstitial cells into steroidogenically active luteinized stromal cells. These nests or islands of luteinized theca cells are scattered throughout the stroma of the ovary, rather than being confined to areas around cystic follicles as in polycystic ovary syndrome (PCOS). These luteinized theca cells result is greater production of androgens.
Seen as a severe form of PCOS, the clinical features of hyperthecosis are similar to those of PCOS. Women with hyperthecosis often have more markedly elevated testosterone, more hirsutism, and are much more likely to be virilized. While elevated androgens in postmenopausal women is rare, hyperthecosis can present in both premenopausal or postmenopausal women. Women with hyperthecosis may or may not have always had underlying PCOS.
Resistant ovary syndrome, previously known as Savage syndrome, is a cause of ovarian failure that can lead to secondary amenorrhea. Resistant ovaries result from a functional disturbance of the gonadotropin receptors in the ovarian follicles. It may be a cause of primary or secondary amenorrhea and is resistant to exogenous gonadotropin stimulation.
Diagnosis of this condition requires that the patient has a normal 46,XX karyotype, normal secondary sexual characteristics, elevated plasma follicle-stimulating hormone and luteinizing hormone – in the menopausal range – and that normal, multiple follicles are seen on ovarian biopsy.
Spontaneous reversal of the receptor resistance may occur.
Follicle-stimulating hormone (FSH) insensitivity, or ovarian insensitivity to FSH in females, also referable to as ovarian follicle hypoplasia or granulosa cell hypoplasia in females, is a rare autosomal recessive genetic and endocrine syndrome affecting both females and males, with the former presenting with much greater severity of symptomatology. It is characterized by a resistance or complete insensitivity to the effects of follicle-stimulating hormone (FSH), a gonadotropin which is normally responsible for the stimulation of estrogen production by the ovaries in females and maintenance of fertility in both sexes. The condition manifests itself as hypergonadotropic hypogonadism (decreased or lack of production of sex steroids by the gonads despite high circulating levels of gonadotropins), reduced or absent puberty (lack of development of secondary sexual characteristics, resulting in sexual infantilism if left untreated), amenorrhea (lack of menstruation), and infertility in females, whereas males present merely with varying degrees of infertility and associated symptoms (e.g., decreased sperm production).
A related condition is luteinizing hormone (LH) insensitivity (termed Leydig cell hypoplasia when it occurs in males), which presents with similar symptoms to those of FSH insensitivity but with the symptoms in the respective sexes reversed (i.e., hypogonadism and sexual infantilism in males and merely problems with fertility in females); however, males also present with feminized or ambiguous genitalia (also known as pseudohermaphroditism), whereas ambiguous genitalia does not occur in females with FSH insensitivity. Despite their similar causes, LH insensitivity is considerably more common in comparison to FSH insensitivity.
Post-testicular factors decrease male fertility due to conditions that affect the male genital system after testicular sperm production and include defects of the genital tract as well as problems in ejaculation:
- Vas deferens obstruction
- Lack of Vas deferens, often related to genetic markers for Cystic Fibrosis
- Infection, e.g. prostatitis
- Ejaculatory duct obstruction