Polycystic ovary syndrome (PCOS) is recognized as the most common endocrine disorder of reproductive-aged women around the world. This document, produced by the collaboration of the American Association of Clinical Endocrinologists and the
Androgen Excess Society aims to highlight the most important clinical issues confronting physicians and their patients with PCOS. It is a summary of current best practices in 2014.
Insulin resistance is believed to play an intrinsic role in the pathogenesis of PCOS. The mechanism by which
insulin resistance or
insulin give rise to
oligomenorrhea and hyperandrogenemia, however, is unclear. Hyperinsulinemic-euglycemic clamp studies have shown that both obese and lean women with PCOS have some degree of
insulin resistance.
Insulin resistance is implicated in the ovulatory dysfunction of PCOS by disrupting the hypothalamic-pituitary-ovarian axis. Given the association with
insulin resistance, all women with PCOS require evaluation for the risk of
metabolic syndrome (MetS) and its components, including
type 2 diabetes,
hypertension,
hyperlipidemia, and the possible risk of clinical events, including acute
myocardial infarction and
stroke. Obese women with PCOS are at increased risk for MetS with
impaired glucose tolerance (IGT; 31 to 35%) and
type 2 diabetes mellitus (T2DM; 7.5 to 10%). Rates of progression from normal
glucose tolerance to IGT, and in turn to T2DM, may be as high as 5 to 15% within 3 years. Data suggest the need for baseline oral
glucose tolerance test every 1 to 2 years based on family history of T2DM as well as body mass index (BMI) and yearly in women with IGT. Compared with BMI- and age-matched controls, young, lean PCOS women have lower
high-density lipoprotein (HDL) size, higher
very-low-density lipoprotein particle number, higher
low-density lipoprotein (
LDL) particle number, and borderline lower
LDL size.
Statins have been shown to lower
testosterone levels either alone or in combination with
oral contraceptives (OCPs) but have not shown improvement in menses, spontaneous ovulation,
hirsutism, or
acne.
Statins reduce total and
LDL cholesterol but have no effect on HDL,
C-reactive protein, fasting
insulin, or homeostasis model assessment of
insulin resistance in PCOS women, in contrast to the general population. There have been no long-term studies of
statins on clinical cardiac outcomes in women with PCOS. Coronary calcification is more prevalent and more severe in PCOS than in controls. In women under 60 years of age undergoing coronary angiography, the presence of polycystic ovaries on sonography has been associated with more arterial segments with >50%
stenosis, but the relationship between PCOS and actual cardiovascular events remains unclear.
Therapies for PCOS are varied in their effects and targets and include both nonpharmacologic as well as pharmacologic approaches.
Weight loss is the primary
therapy in PCOS--reduction in weight of as little as 5% can restore regular menses and improve response to ovulation- inducing and fertility medications.
Metformin in premenopausal PCOS women has been associated with a reduction in features of MetS. Clamp studies using
ethinyl estradiol/drosperinone combination failed to reveal evidence of an increase in either peripheral or hepatic
insulin resistance. Subjects with PCOS have a 1.5-times higher baseline risk of venous thromboembolic disease and a 3.7-fold greater effect with OCP use compared with non-PCOS subjects. There is currently no genetic test to screen for or diagnose PCOS, and there is no test to assist in the choice of treatment strategies. Persistent
bleeding should always be investigated for pregnancy and/or uterine pathology--including transvaginal ultrasound exam and endometrial biopsy--in women with PCOS. PCOS women can have difficulty conceiving. Those who become pregnant are at risk for
gestational diabetes (which should be evaluated and managed appropriately) and the microvascular complications of diabetes. Assessment of a woman with PCOS for
infertility involves evaluating for preconceptional issues that may affect response to
therapy or lead to adverse pregnancy outcomes and evaluating the couple for other common
infertility issues that may affect the choice of
therapy, such as a semen analysis. Women with PCOS have multiple factors that may lead to an elevated risk of pregnancy, including a high prevalence of IGT--a clear risk factor for
gestational diabetes--and MetS with
hypertension, which increases the risk for
pre-eclampsia and
placental abruption. Women should be screened and treated for
hypertension and diabetes prior to attempting conception. Women should be counseled about
weight loss prior to attempting conception, although there are limited clinical trial data demonstrating a benefit to this recommendation. Treatment for women with PCOS and anovulatory
infertility should begin with an oral agent such as
clomiphene citrate or
letrozole, an
aromatase inhibitor.