PCOS, POS, Polycystic Ovarian Syndrome, hyperandrogenic anovulation (HA), hyperandrogenic syndrome (HAS), Stein - Leventhal syndrome, functional ovarian hyperandrogenism, ovarian hyperthecosis, sclerocystic ovary syndrome.
HAS is defined as production of excessive amounts of male hormones (androgens), in particular testosterone , by either one or a combination of the following :
PCOs – polycystic ovaries syndrome acquired its most widely used name due to the common sign on ultrasound examination of multiple (poly) ovarian cysts. These"cysts" are actually immature follicles not cysts. The follicles have developed from primordial follicles, but the development has stopped ("arrested") at an early antral stage due to the disturbed ovarian function. The follicles may be oriented along the ovarian periphery, appearing as a 'string of pearls'on ultrasound examination.
Women with PCOS experience an increased frequency of hypothalamic GnRH pulses, which in turn results in an increase in the LH/FSH ratio.
A majority of people with PCOS have insulin resistance. Their elevated insulin levels contribute to or cause the abnormalities seen in the hypothalamic-pituitary-ovarian axis that lead to HAS (PCOS). Hyperinsulinemia increases GnRH pulse frequency, LH over FSH dominance, increased ovarian androgen production, decreased follicular maturation, and decreased SHBG binding; all these steps contribute to the development of PCOS. Insulin resistance is a common finding among women with a normal weight as well as overweight women.
Adipose tissue possesses aromatase, an enzyme that converts androstenedione to estrone and testosterone to estradiol. The excess of adipose tissue in obese women creates of having both excess estrogens which inhibits FSH via negative feedback.
PCOS may be associated with chronic inflammation, with several investigators correlating inflammatory mediators with anovulation and other PCOS symptoms. Similarly, there seems to be a relation between PCOS and increased level of oxidative stress.
PCOS is a heterogeneous disorder of uncertain cause. There is strong evidence that it is a genetic disease. Such evidence includes the familial clustering of cases, greater concordance in monozygotic compared with dizygotic twins and heritability of endocrine and metabolic features of PCOS.
The genetic component appears to be inherited in an autosomal dominant fashion with high genetic penetrance but variable expressivity in females; this means that each child has a 50% chance of inheriting the predisposing genetic variant(s) from apparent, and, if a daughter receives the variant(s), the daughter will have the disease to some extent. The genetic variant(s) can be inherited from either the father or the mother, and can be passed along to both sons (who may be asymptomatic carriers or may have symptoms such as early baldness and/or excessive hair) and daughters,who will show signs of PCOS. The phenotype appears to manifest itself at least partially via heightened androgen levels secreted by ovarian follicle theca cells from women with the allele. The exact gene affected has not yet been identified. In rare instances, single-gene mutations can give rise to the phenotype of the syndrome. Current understanding of the pathogenesis of the syndrome suggests, however, that it is a complex multigenic disorder.
Polycystic ovary disease (PCOS) is a hormonal imbalance in women that is thought to be one of the leading causes of female infertility. Polycystic ovary syndrome causes more than 75% of cases of anovulatory infertility. Not all women with PCOS have difficulty becoming pregnant. For those who do, anovulation is a common cause. The mechanism of this anovulation is uncertain, but there is evidence of arrested antral follicle development,which, in turn, may be caused by abnormal interaction of insulin and luteinizing hormone (LH) on granulose cells.
Endocrine disruption may also directly decrease fertility, such as changed levels of gonadotropin-releasing hormone, gonadotropins (especially an increase in luteinizing hormone), hyperandrogenemia, and hyperinsullinemia. Gonadotropins are released by gonadotroph cells in pituary gland, and these cells appear to harbor insulin receptors, which are affected by elevated insulin levels. A reason that insulin sensitizers work in increasing fertility is that they lower total insulin levels in body as metabolic tissues regain sensitivity to the hormone. This reduces the overstimulation of gonadotroph cells in pituitary.
The prevalence of obesity has increased worldwide in the last few decades. Obesity status is defined according to the body mass index (BMI=body weight in kilograms divided by height inmeters2) of 30 kg/m2 or more. BMI of 25 to 29.9 kg/m2 is defined as ‘overweight’, while BMI of less than 25 kg/m2 is considered normal. This had significant impact on the development of chronic diseases such as the metabolic syndrome, coronary heart disease and type 2 diabetes. Also, central obesity can be diagnosed clinically by measuring the waist circumference (WC) larger than 88 cm or waist-to-hip circumference ratio (WHR) greater than 0.85, confer high risk for metabolic complications in obese individuals with BMI between 25.0 and 34.9 kg/m2.
However, obesity is a common finding in women with PCOS and between 40–80% of women with this condition is reported to be overweight, obese or centrally obese depending onthe setting of the study and the ethnical background of the subjects. Obesity has a worse additive effect on features of PCOS such as insulin resistance,hyperandrogenism, infertility, hirsutism and pregnancy complications.
The relationship between PCOS and obesity is complex, and most likely involves interaction of geneticand environmental factors. The most frequent type of obesity in PCOS is the obesity of central variety. It is shown that central obesity is associated with increased risk for diabetes, hyperlipidemia, hypertension,atherosclerosis, and insulin resistance. Fat localized in the upper body is correlated with significantly reduced overall clearance of insulin, which contributes to hyperinsulinemia.
However, obese and non-obese PCOS patients may have differences in clinical manifestations. The differences in biochemical and clinical features between obese and non-obesePCOS patients allow determining, to some degree, the contributions of obesity to the clinical manifestations of PCOS. Differences in menstrual function have been reported, with obese patients exhibiting a greater prevalence of oligoamenorrhea and anovulation than non-obese women, and the prevalence of infertility has been increasing in obese PCOS patient . Also, it is known that obesity has a direct link to the degree of hirsutism in PCOS patients. Obese women with PCOS had a greater prevalence of hirsutism, acanthosis nigricans, than non-obese patients, reflecting a higher prevalence and magnitude of insulin resistance and hyperinsulinemia among obese PCOS patients. Impaired glucose tolerance, type 2 diabetes mellitus and the dyslipidemia has highest risk in obese PCOS patients. Overall, given the prevalence of risk factors for atherosclerosis in women with PCOS, a higher prevalence of cardiovascular events in these patients can be expected. In addition, obese PCOS patients have higher prevalence of endometrial carcinoma than non-obese PCOS women. Anovulation, unopposed estrogen stimulation, and hyperinsulinemia may play a role in the increased risk of this gynecologic carcinoma in PCOS patients.Also, it is reported that obstructive sleep apnea, pregnancy complications such as preeclampsia, gestational induced hypertension and gestational diabetes are more prevalent in obese PCOS patient.
However, the impact of obesity on PCOS therapy is very important. Therapeutic modalities directed at the reduction of hyperinsulinemia (weight loss or insulin-sensitizing agents)appear to ameliorate symptoms of PCOS and restore normal ovarian function in obese women with PCOS.
Weight loss, especially more than 5 % of the baseline weight, is the first-line therapy in treatment of these women. It leads to hormonal,menstrual, and metabolic improvement with reduced serum concentrations of free testosterone in obese women with PCOS. The mechanism by which weight loss leads to a reduction of hyperandrogenism appears to involve improved insulin sensitivity with a resultant decline in circulating insulin levels. Bariatric surgery may be recommended for morbidly obese women .
There is insufficient evidence to conclude an effect from D-chiro-inositol. Myo-inositol however appears to be effective based on asystematic review. There is preliminary evidence but no high quality evidencelooking at acupuncture in PCOS.
Medications for PCOS include oral contraceptives and metformin. The oral contraceptives increase sex hormone binding globulin production,which increases binding of free testosterone. This reduces the symptoms of hirsutism caused by high testosterone and regulates return to normal menstrual periods. Metformin is a drug commonly used in type 2 diabetes to reduce insulin resistance, and is used off label (in the UK, US, and EU) to treatinsulin resistance seen in PCOS. In many cases, metformin also supports ovarian function and return to normal ovulation. Spironolactone can be used for its antiandrogenic effects, and the topical cream eflornithine can be used to reduce facial hair. A newer insulin resistance drug class, the thizalidinediones (glitazones),have shown equivalent efficacy to metformin, but metformin has a more favorable side effect profile. The United Kingdom's National Institue for Health and Clinical Excellence recommended in 2004 that women with PCOS and a bodymass index above 25 be given metformin when other therapy has failed to produce results. Metformin may not be effective in every type of PCOS, and therefore there is some disagreement about whether it should be used as a general first line therapy. It can be difficult to become pregnant with PCOS because it causes irregular ovulation. Medications to induce fertility when trying to conceive include the ovulation inducer clomiphene or pulsatile leuprolide. Metforminim proves the efficacy of fertility treatment when used in combination with clomiphene. Metformin is thought to be safe to use during pregnancy ( pregnancy category B in the US). A review in 2014 concluded that theuse of metformin does not increase the risk of major birth defects in women treated with metformin during the first trimester.
Another pharmacotherapy which can be used is called myo-inositol. Some studies suggested that myo-inositol could play an important role in cellular morphogenesis and cytogenesis, in the synthesis of lipids, in the creation of cell membranes and in cell growth. It is also a precursor of phospholipids, which are responsible for the generation of important intracellular signals in mammalian oocytes and in the resumption of meiotic maturation.
Myo-inositol also regulates, via signal transduction pathways, the secretion of some exocrine glands such as pancreas and other organs, including the ovaries. In the oocytes these intracellular pathways are involved in the release of cortical granules, in the inhibition of polyspermy, in the completion of meiosis and in the activation of the cell cycle that subsequently results in embryonic development. It has been hypothesized that intrafollicular myo-inositol concentration and oocyte quality might be connected because inositol phospholipids (of which myo-inositol is a precursor) are held responsible for important intracellular signals essential for oocyte development, and because myo-inositol itself seems to improve oocytes in vitro maturation.
Surgery can be attempted in case of inefficient result with medications for ovulation induction. Though surgery is not commonly performed, the polycystic ovaries can be treated with a laparoscopic procedure called ovarian drilling (puncture of 4-10 small follicles with electrocautery), which often results in either resumption of spontaneous ovulations or ovulations after adjuvant treatment with clomiphene or FSH.
A disease of excess body fat that can have a negative effect on health, leading to reduced life expectancy and other health problems.
Failure of the ovaries to release an oocyte over a period of time generally exceeding 3 months.
An abnormal condition in a woman's menstrual cycle.
A medical term which describes a diminished functional activity of the gonads – the testes and ovaries.
Cancer that arises from the endometrium, the lining of the uterus.
The absence of a menstrual period in women of reproductive age.
Thickening of the lining of the uterus.
A type of cancer in which abnormal cells begin to grow in one or both of a woman's ovaries.
Light or infrequent menstrual ﬂow at intervals of 39 days to 6 months or 5–7 cycles in a year.
The presence of abnormally high levels of prolactin in the blood.
The luteinisation of ovulatory follicle without a release of an oocyte.
Various types of conditions that can affect the function of the heart or blood vessels, which may have the negative effect also to the infertility
Repetitive nocturnal complete collapses (apneas) or partial collapses (hypopneas) of the upper airway during sleep.
The thickening, hardening and loss of elasticity of the walls of arteries.
Abnormally elevated levels of any or all lipids in the blood.
Excess levels of insulin circulating in the blood relative to the level of glucose and impairing the hormonal levels, even those involved in reproduct
The ovum-producing organs of the internal female reproductive system
An endocrine gland, about the size of a pea, whose secretions control the other endocrine glands and influence growth, metabolism, and maturation.
A female germ cell involved in reproduction.
The primary female sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics.
FSH is a hormone secreted by the anterior pituitary gland. It regulates the development, growth, pubertal matur and reproductive functions of the body
A peptide hormone that decreases blood glucose levels.
A hormone, that stimulates ovulation and the development of the corpus luteum in females, and the production of androgens in males.
Steroid hormone, secreted by the ovaries, whose function is to prepare the uterus for the implantation of a fertilized ovum and to maintain pregnancy.
Steroid hormone produced primarily in the testes of the male; responsible for the development of secondary sex characteristics in the male.
Development of ovarian follicles from primordial to tertiary under the stimulation of gonadotropins.
The release of egg(s) from the ovaries.
Occurrence of menstruation in 11 years or less.
The development of pubic hair before the age of 8 years in females and 9 years in males, without other signs of puberty.
An isolated appearance of breast development, usually in girls younger than 3 years.
A mental disorder defined by abnormal eating habits that negatively affect a person's physical or mental health.
Predisposition to developing polycystic ovary syndrome (PCOS).
Serum level of AMH (Anti-Müllerian hormone) above the upper limit of the reference range.
A medical condition characterized by an excessive amount of estrogenic activity in the body.
A condition with high blood luteinizing hormone (LH) leading to irregular periods and reduced fertility in both females and males.
A condition characterized by excessive levels of testoterone in the body.
An elevated blood pressure, clinically defined as at or greater than 140/90 (systolic/diastolic) mmHg.
A type of lifestyle with little or no physical activity.
A condition with low serum follicle–stimulating hormone (FSH) concentration.
A medical condition of excess body fat that can have a negative effect on health, leading to reduced life expectancy and other health problems.
Disturbance in the balance of free radicals and antioxidant defenses which can affect oocyte maturation, fertilization, and embryo development.
Eating habits are one of the few factors within our control that impact not only our chances of falling pregnant.
Type of lifestyle with no or irregular physical activity.
A long-term skin condition characterized by areas of blackheads, whiteheads, pimples, greasy skin, and possibly scarring.
The emotional state characterized by unpleasant feelings such as uneasiness, worry, apprehension and dread.
Normal or spontaneous atrophy or shrinkage of the breasts.
A prolonged condition in which tissue injury and attempts at repair coexist, leading to tissue remodeling and dysfunction.
A condition with low serum follicle-stimulating hormone (FSH) concentration.
The emotional state characterized by persistent feel of low self-esteem, loss of interest, sadness and negative attitude.
The onset of puberty before the average age in girls (8 years).
A condition with high serum estrogen hormone concentration and thus harms sperm production and menstrual periods.
The condition when there are elevated levels of insulin within the blood in relation to levels of glucose.
A condition with high serum luteinizing hormone (LH) concentration.
The presence of elevated testosterone concentration within the circulating blood.
The excessive hairiness on women in those parts of the body where terminal hair normally is absent or minimal, such as a beard or chest hair.
A hair loss that frequently occurs due to an underlying susceptibility of hair follicles to androgenic miniaturisation.
Abnormally heavy or prolonged bleeding in menstrual periods.
Unusually increased sexual desires and urges.
The medical term for infrequent, often light menstrual periods (intervals exceeding 35 days).
Irregular menstruation is a menstrual disorder whose manifestations include irregular cycle lengths as well as metrorrhagia
A fluid-filled sac or pockets that develops on a woman's ovary.
Body weight that's greater than what is considered healthy for a certain height.
Pauses in breathing or periods of shallow breathing during sleep.
The biological development of sex differences, changes that make a male body different from a female body.
A form of alternative medicine and a key component of traditional Chinese medicine involving thin needles inserted into the body at acupuncture points
A variety of surgical procedures to reduce weight performed on people who have obesity.
Process by which a woman donates eggs for purposes of assisted reproduction or biomedical research.
A micromanipulative fertilization technique in which a single sperm is injected directly into an egg.
A surgical treatment that can trigger ovulation in women with polycystic ovary syndrome (PCOS).
Medications used in the management of polycystic ovary syndrome.
Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness.
The procedure in which a man (sperm donor) provides his sperm for fertility treatment.
A process in which an egg is fertilised by sperm outside the body: in vitro. Own or donated gametes may be used.