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Polycystic Ovary Syndrome – A Simplified Approach to Diagnosis

by Jennifer F. Kawwass, MD and Heather S. Hipp, MD

Polycystic Ovary Syndrome, or PCOS, the enigmatic syndrome ascribed to infertile, overweight females with irregular menstrual cycles, may be simpler to understand than it seems. The syndrome can be confusing: no clear linear causal pathway has been elucidated, and many endocrine axes interact to accentuate the classical physical manifestations. In addition, it is a broad diagnosis, and many women with PCOS do not fit the stereotypical PCOS mold.

Despite the heterogeneity of women that can meet criteria for PCOS, understanding the diagnostic basics can make the syndrome much easier to recognize.

Importantly, the diagnosis is independent of body mass index (BMI) or weight. In fact, 10-15 percent of women with PCOS are lean with a normal BMI. According to the 2003 NIH Rotterdam criteria, a diagnosis of PCOS requires two of the following three characteristics:

1. Oligoovulation and/or anovulation (i.e. irregular menstrual cycles)
Can be determined by patient history: menstrual cycles occurring in an unpredictable pattern or greater than 42 days apart are suggestive of anovulation.

2. Elevated androgens (clinical and/or biochemical)
Can be determined by laboratory value of testosterone above the female reference range or by clinical signs of hirsutism/ acne that exceed ethnic norms.

3. Polycystic appearing ovaries on transvaginal ultrasound
Can be determined by ultrasound assessment of the ovaries having a “PCOS” appearance. A formal antral follicle count (12 or more follicles measuring 2-9mm in diameter) on each ovary can also be done.

Although AMH is not part of the diagnostic criteria, an elevated AMH (e.g. over 4 ng/mL) in combination with the other diagnostic criteria is suggestive of PCOS.

Given that the criteria only requires two of the three above characteristics, women may have PCOS without hyperandrogenism or irregular cycles. There is a sub-category of women with PCOS who are lean (aka “lean PCOS”). These women often do not have hyperandrogenism and present with infertility due to anovulation. Due to their BMI, they are sometimes diagnosed with functional hypothalamic amenorrhea (see below), which is treated in a different fashion.

The primary tenet in diagnosing PCOS is appreciation that it is a diagnosis of exclusion. One can only clearly diagnose a woman as having PCOS after ruling out all potential masqueraders. As women with PCOS often present with irregular or absent menstrual cycles, excluding other causes of amenorrhea or oligomenorrhea is usually a good place to start. Common masqueraders include pregnancy, thyroid disease and hyperprolactinemia, which can be assessed with a laboratory evaluation including bHCG, a TSH a prolactin. A more rare cause is delayed onset congenital adrenal hyperplasia (CAH), which is screened for with 17-hydroxyprogesterone.

On a patient-specific basis, one can also screen for other rare causes of oligomenorrhea: Cushing’s syndrome in someone with rapid weight gain and new-onset hypertension, an ovarian or adrenal testosterone-secreting tumor in an individual with rapid-onset severe virilization, or acromegaly in someone with increasing glove, shoe or hat size. Most often, however, ruling out pregnancy, pituitary and thyroid disease, and CAH is a reasonable place to start.

Particularly in a lean woman with absent cycles, functional hypothalamic amenorrhea (FHA) may cause absent periods and may even be present in addition to underlying PCOS. Women with FHA typically present with a low BMI and a history consistent with excessive exercise or calorie restriction. If the FSH, LH, and estradiol are all low or in the low range of normal, referral to a reproductive endocrinologist for help with treatment of FHA would be reasonable.

Lastly, severe diminished ovarian reserve can cause irregular cycles. It can be very helpful to ascertain ovarian reserve and hypothalamic-pituitary-ovarian function. An overweight patient with irregular cycles may actually have diminished ovarian reserve and not PCOS. Obesity and irregular cycles are not synonymous with PCOS. An FSH and estradiol in the early follicular phase or after a progesterone-induced bleed may help clarify ovarian reserve in a patient that is not on oral contraceptives. An FSH over 10 would suggest diminished ovarian reserve and not PCOS. An anti-mullerian hormone (AMH) or transvaginal ultrasound with antral follicle count (AFC) may also help in the differentiation.

Figure 1. Simplified Approach to Diagnosing PCOS

Adolescents are a unique population. Because of young age and resultant robust ovarian reserve, polycystic ovarian morphology may not necessarily represent PCOS. Moreover, oligomenorrhea is normal around the time of menarche. Some researchers argue that to give a diagnosis of PCOS to an adolescent, she must have all three of the Rotterdam criteria.

Lifestyle counseling is warranted in women with a diagnosis of PCOS. For women who are overweight, a 5-10 percent weight loss has been associated with improvement in menstrual regularity and resumption of menses. Counseling regarding heightened risk of insulin resistance compared to women without PCOS may also help guide dietary and exercise choices for patients with the syndrome. Finally, when not trying to conceive, the importance of uterine lining protection with some form of hormonal contraception, including intrauterine devices, is worth discussing.

The next step is to determine fertility intentions. The treatment course diverges based on desire for either fertility or contraception. For those who are not currently interested in conceiving, oral contraceptive pills (OCPs) are often the first line of treatment. OCPs offer endometrial lining protection and can also improve symptoms of hyperandrogenism.

For those who desire pregnancy, the first line agent for ovulation induction is letrozole. Referral to an REI is reasonable before attempt at ovulation induction or after one to three cycles of failed attempts at pregnancy with the use of ovulation induction.

Women who have PCOS are at a higher lifetime risk of diabetes and, when pregnant, gestational diabetes, even if they are lean. Screening for diabetes should be strongly considered in any women with PCOS; this can be done with a hemoglobin A1c or a 2-hour oral glucose tolerance test. If pre-diabetes is diagnosed, Metformin can be offered to aid in insulin resistance and, in some women, weight loss.

It is also possible that someone on the PCOS-spectrum may develop more overt symptoms with weight gain. As such, a female with mild PCOS may benefit from counseling regarding the avoidance of weight gain.

PCOS affects 10-15 percent of reproductive-age women. As a result, it warrants the attention of not only obstetrician gynecologists, but also physicians in other specialties. The associated cardiovascular, endocrine and fertility sequelae can impact all aspects of a PCOS female’s medical care.


References
Carmina, E, Oberfield, SE, Lobo, RA. “The diagnosis of polycystic ovary syndrome in adolescents.” Am J Obstet Gynecol; 2010; 03 (3): 201. E1-5.

Good C, Tulchinsky M, et al. “Bone Mineral density and body composition in lean women with polcystic ovary syndrome.” Fertility and Sterility 1999; 72: 21-25.

Goodman NF, Cobin RH, et al. “American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society Disease State Clinical Review: Guide to the Best practices in the Evaluation and Treatment of Polycystic Ovary Syndrome- Part 2.” Endocr Pract 2015; 21: 1415-1426

Goyal, M, Dawood, AS. “Debates regarding lean patients with polycystic ovary syndrome: A narrative review.” J Hum Reprod Sci. 2017; 10 (3): 154-161.

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