Polycystic Ovary Syndrome and Hirsutism

Chapter 546 Polycystic Ovary Syndrome and Hirsutism




Polycystic Ovary Syndrome




Pathology Pathogenesis and Genetics


PCOS has a high concordance rate in twins, and in some studies either epigenetic or dominant inheritance patterns are observed. Nonetheless, a consistent hereditary pattern has not been identified.


Gonadotropic dysregulation with increased luteinizing hormone (LH) pulsatility and abnormally high ratios of circulating LH to follicle-stimulating hormone (FSH) are found in many patients with PCOS. Increased ovarian production of androgen in response to LH and impaired folliculogenesis owing to lower FSH are attributed to this gonadotropic pattern. Abnormal regulation of gonadotropin-releasing hormone agonist (GnRH) and abnormal gonadotropin secretion more likely reflect the abnormal hormonal milieu of the syndrome than explain its origin (Fig. 546-1). An increased ratio of circulating levels of LH to FSH is not a diagnostic criterion for PCOS.



Alterations in activities of steroidogenic enzymes that would explain ovarian androgenic hyperfunction are seen in PCOS subjects, but they are not consistently present in all patients; it is unclear whether these alterations cause PCOS or are a consequence of ovarian dysregulation. The mass of ovarian stromal cells responsible for androgen production is increased, and surgery that reduces this ovarian component (ovarian wedge resection, or laparoscopic ablative procedures) reduces circulating androgen levels and often restores ovarian cyclicity. Patients with hyperandrogenic congenital or adult-onset adrenal hyperplasia exhibit PCOS-like ovarian dysfunction that can be reversed by reducing the adrenal-derived androgens with glucocorticoid therapy. A primary role for androgen excess in the pathophysiology of all instances of PCOS seems unlikely; many patients have minimal hyperandrogenism, and elimination of androgen excess (with GnRH agonists) does not affect associated insulin resistance.


Measures of insulin resistance are greater and more prevalent among women with PCOS than controls even when accounting for BMI. Insulin enhances ovarian androgen production directly and contributes to elevations of free testosterone levels through its suppression of hepatic production of sex steroid–binding globulin. Treatment with insulin sensitivity–enhancing agents that can reduce insulin levels is associated with modest reductions in measures of androgen excess and, in some patients, restoration of regular ovulation. The association of insulin resistance with weight might explain the appearance of features of PCOS among some women who gain weight and the resolution of PCOS among affected women who lose weight.



Clinical Manifestations


PCOS commonly becomes manifest as puberty progresses, but its onset can occur later during young adulthood. PCOS is a lifelong disorder (though with some evidence for amelioration with age or weight loss) (Table 546-2). Clinical hallmarks are menstrual abnormalities and manifestations of hyperandrogenism. Ovulation is typically irregular or absent, and menses are consequently irregular or absent. When they do occur, menses may be relatively normal in character as a consequence of a preceding ovulation. In many women, protracted periods of unopposed estrogen exposure without ovulation can terminate erratically in bleeding that is abnormally prolonged and/or heavy.



Table 546-2 LIFELONG HEALTH COMPLICATIONS

























PRENATAL OR CHILDHOOD ADOLESCENCE, REPRODUCTIVE YEARS POSTMENOPAUSAL
REPRODUCTIVE









Delayed menopause?
METABOLIC
Abnormal fetal growth









OTHER
 


Cardiovascular disease?

From Norman RJ, Dewailly D, Legro RS, et al: Polycystic ovary syndrome, Lancet 370:685–696, 2007.


The diagnosis of PCOS in adolescents may be made on the basis of a lack of resolution of the normal pattern of anovulatory menstrual cycles present in the first 1 or 2 postmenarcheal years. Less commonly, the diagnosis is made in the setting of primary amenorrhea. Serum androgen levels may be elevated and clinical findings of androgen excess are common, though distinction of normal androgenic expressions of puberty (acne, mild hirsutism) from early manifestations of PCOS may be difficult.


Obesity is common among affected women, and in some patients expression of PCOS features is conditional on elevation of BMI and reversible with weight loss. A subset of patients present with a “lean” PCOS phenotype; absence of excess weight should not preclude consideration of the PCOS diagnosis. PCOS is associated with an increased prevalence of insulin resistance and type 2 diabetes independent of the tendency for many affected patients to have an elevated BMI. Additionally, PCOS confers a substantial and specific increase in risk for metabolic syndrome (hyperlipidemia, insulin resistance, type 2 diabetes) in adolescent girls after accounting for BMI.


Jun 18, 2016 | Posted by in PEDIATRICS | Comments Off on Polycystic Ovary Syndrome and Hirsutism

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