Endocrinology and Metabolism Clinics of North America
POLYCYSTIC OVARY SYNDROME
Section snippets
POLYCYSTIC OVARIES
Based on the two-cell, two-gonadotropin theory of ovarian steroidogenesis, androgens produced by LH-stimulated thecal cells undergo aromatization to estrogens by follicle-stimulating hormone (FSH)–stimulated granulosa aromatase.48 A shift from an androgenic to an estrogenic ovarian microenvironment occurs as aromatase activity increases within the developing follicle. In hyperandrogenic anovulatory women, because the preovulatory follicle does not develop, multiple small subcapsular follicles
GENETIC STUDIES
Because PCOS is a heterogeneous disorder, it is unlikely that its variability is the result of the dysfunction of a single gene. Moreover, determining the inheritance of PCOS is difficult because the disorder affects reproductive-aged women, and there is no clearly described male phenotype. Nevertheless, familial groupings of PCOS suggest an autosomal dominant mode of inheritance with reduced penetrance and premature balding in men as a possible male phenotype.24 A high degree of discordance
Menstrual Irregularity
Hyperandrogenic anovulatory women usually notice the peripubertal onset of amenorrhea or menstrual irregularity defined as menses occurring at less than 21 or greater than 35 day intervals. Patients wishing to conceive also experience infertility from anovulation. The acyclic estrogen production unopposed by progesterone stimulates endometrial proliferation, thereby increasing the risk for endometrial hyperplasia and cancer23 and, possibly, breast cancer.51
Hirsutism
Most hyperandrogenic anovulatory women
Hypothalamic-Pituitary Unit
Serum immunoactive and bioactive LH levels are elevated in approximately 70% of women with hyperandrogenic anovulation. An elevated LH pulse amplitude accompanied by an increased LH pulse frequency in some individuals causes a two to three fold elevation in serum LH in comparison with FSH.42 LH hypersecretion, in part, reflects the consequence of acyclic estrogen production unopposed by progesterone, because estrogen sensitizes the pituitary to gonadotropin-releasing hormone (GnRH), enhances
Sex Steroid Abnormalities
Women with classic PCOS have elevated serum levels of T, A4, DHEA, DHEAS,53 and 17-OHP.33 The ovary is the source of excess A4, T, and 17-OHP; the adrenal is responsible for increased amounts of DHEA and DHEAS. Hyperandrogenemia stimulates androgen-dependent target tissues; suppresses hepatic SHBG production, thereby increasing the portion of T not bound to SHBG (free T); and increases extraglandular aromatization by skin, muscle, brain, and adipose tissue.54
Estrone (E1), the major serum
LABORATORY ANALYSIS
Based on the NIH definition of PCOS, the purpose of diagnostic testing in hyperandrogenic anovulatory women is to exclude other endocrinopathies, including virilizing tumors, adult-onset CAH, hyperprolactinemia, and Cushing's syndrome.32 Other causes of androgen excess and menstrual irregularity include drugs [e.g., anabolic steroids, 19-norsteroids, danazol (Danocrine), synthetic progestins] and conditions unique to pregnancy (e.g., luteoma, hyperreactio luteinalis).
The diagnosis of
IMAGING STUDIES
The presence of virilization or severe rapidly progressive hirsutism regardless of serum T and DHEAS levels may require a complete evaluation to distinguish patients with severe PCOS from those with a possible virilizing tumor.
Transvaginal ultrasonography (TVUS) detects ovarian masses less than 1 cm in size and identifies 90% of all virilizing ovarian tumors.38 TVUS does not always distinguish an ovarian tumor from a corpus luteum cyst, thus any abnormal ovarian finding on sonography must be
THERAPY
The goals of therapy are to normalize the endometrium, antagonize androgen action on target tissues, reduce insulin resistance, and correct anovulation, if necessary.
SUMMARY
The cardinal clinical features of PCOS are hirsutism and menstrual irregularity from anovulation. Obesity occurs in approximately 50% of hyperandrogenic anovulatory women, some of whom also have non–insulin-dependent diabetes mellitus. Underlying these clinical findings are several biochemical abnormalities, including LH hypersecretion, hyperandrogenism, acyclic estrogen production, decreased SHBG capacity, and hyperinsulinemia, all of which contribute to increased ovarian production of
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Oxidative stress and cardiovascular complications in polycystic ovarian syndrome
2015, European Journal of Obstetrics and Gynecology and Reproductive BiologyCitation Excerpt :Carotid intima-media thickness is another surrogate marker for early atherogenic process that has also been found to be increased in PCOS compared with the age-matched control [80]. A large body of evidence indicate that the prevalence of metabolic syndrome and coronary artery disease (CAD) is higher in PCOS [2,4,44,80–90]. These findings unmask the increased risk of PCOS women for adverse cardiovascular outcomes and mortality.
Hirsutism and Virilization in the Female
2013, The Immunoassay Handbook: Theory and Applications of Ligand Binding, ELISA and Related TechniquesHirsutism and Virilization in the Female
2013, The Immunoassay HandbookHow to recognize PCOS: Results of a web-based survey at IVF-worldwide.com
2013, Reproductive BioMedicine OnlineCitation Excerpt :Since the disorder was first described in 1935 by Stein and Leventhal (1935), the definition of PCOS has evolved significantly. In 1990, the National Institutes of Health (NIH) established diagnostic criteria for PCOS which called for clinical and/or laboratory evidence of hyperandrogenism and oligoanovulation, with the exclusion of other causes of hyperandrogenism such as adult-onset congenital adrenal hyperplasia, hyperprolactinaemia and androgen-secreting neoplasms (Goudas and Dumesic, 1997). In 2003, another conference of experts was convened in Rotterdam, the Netherlands.
Address reprint requests to Daniel A. Dumesic, MD, Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Charlton 4A, The Mayo Clinic, 200 First Street SW, Rochester, MN 55905