Polycystic ovary syndrome (PCOS): Clinical sciences

Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in reproductive-aged biological females and is characterized by a combination of anovulation, clinical or biochemical hyperandrogenism, and multiple small cysts in the ovaries. Additionally, a lot of patients with PCOS have some degree of metabolic abnormalities, such as insulin resistance. The anovulation and hyperandrogenism often result in additional symptoms in patients, ranging from amenorrhea to abnormal uterine bleeding, as well as infertility. So overall, management of PCOS focuses on addressing the key findings in each patient, whether that’s infertility, hyperandrogenism, or insulin resistance.

Your first step in evaluating a patient who presents with a chief concern suggesting polycystic ovary syndrome is to obtain a focused history and physical exam. Individuals with PCOS typically report menstrual abnormalities. Be sure to ask about their menstrual history, including the length of their cycles from the first day of one period to the first day of the next, in the absence of hormonal contraception use. Typically, patients with PCOS will report signs of ovulatory dysfunction, meaning irregular menstrual cycles, which are either shorter than 21 days or longer than 35 days.

Another common presentation is secondary amenorrhea, meaning the absence of menses for 3 or more consecutive months after menarche. Ovulatory dysfunction in PCOS can lead to female factor infertility, which might be the patient’s primary concern. Patients may also report the gradual onset of coarse dark hair growth in androgen-sensitive locations, such as the face, chest, back, and abdomen. This is characteristic of hirsutism related to PCOS.

On physical exam, you may notice evidence of hyperandrogenism, including hirsutism, acne, and possibly androgenic alopecia. Your patient may also show signs of insulin resistance, such as elevated body mass index, or BMI, above 25, and centripetal fat distribution, which is indicated by a waist circumference greater than 35 inches; as well as acanthosis nigricans, which are brown velvety plaques found in flexural areas, such as the neck, axillae or the groin. Some patients may also have hypertension. However, keep in mind that the pelvic examination is typically normal.

Alright, since most of these patients have a history of irregular menses or amenorrhea, the first step should be ruling out pregnancy by obtaining an hCG level. If hCG is positive, diagnose pregnancy and counsel your patient to initiate prenatal care. On the other hand, if hCG is negative, suspect PCOS and proceed with additional testing.

Begin by checking labs which aid in confirming your diagnosis. Laboratory tests are ideally obtained between days 3 and 5 of the menstrual cycle, and they serve to document biochemical hyperandrogenemia and to exclude other causes of ovulatory dysfunction and hyperandrogenism.

These labs include total testosterone and sex hormone binding globulin, or SHBG - with the latter being useful in estimating free testosterone levels; Dehydroepiandrosterone sulfate, or DHEAS; 17-hydroxyprogesterone, or 17-OHP; thyroid stimulating hormone, or TSH; prolactin, luteinizing hormone, or LH; follicle-stimulating hormone, or FSH; and estradiol. Additionally, a progesterone level on day 20 or 21 of the menstrual cycle should be obtained to assess ovulatory status. In addition to these labs, order a pelvic ultrasound.

With PCOS, free and total testosterone, and/or DHEAS levels are elevated; but keep in mind that severely elevated levels could indicate ovarian or adrenal androgen-secreting tumors. 17-OHP levels are normal in PCOS, but elevated levels could suggest nonclassical congenital adrenal hyperplasia, a condition that is clinically identical to PCOS. Additionally, TSH and prolactin levels are typically normal, but if elevated, could suggest thyroid hormone imbalances or hyperprolactinemia, both of which could cause ovulatory dysfunction.

Luteinizing hormone, or LH, can be mildly elevated, especially when compared to follicle-stimulating hormone or FSH. Normal FSH and estradiol levels rule out ovarian failure as the cause of amenorrhea. Lastly, a progesterone level less than 4 on day 20 or 21 of the menstrual cycle suggests anovulation.

On the flip side, a pelvic ultrasound can show polycystic ovarian morphology defined as 20 or more follicles per ovary, on either ovary; or an ovarian volume of 10 mL or greater on either ovary. Follicles should measure between 2 and 9 mm, and no corpus luteum, cyst, or dominant follicle should be present.

Here’s a clinical pearl: Currently there are two different criteria for diagnosing polycystic ovarian morphology on ultrasound in the adult patient. One uses a lower threshold of 12 or more follicles located peripherally in the ovarian cortex; while the other uses at least 20. This is based on the ability of Ultrasound to accurately detect these follicles, which depends on the machine's resolution.

You might also see a thickened endometrium caused by unopposed estrogen levels that are common with anovulation.

Here's a high-yield fact! Patients with PCOS and anovulation are at increased risk of endometrial cancer due to the effects of unopposed estrogen on the endometrium. Keep in mind that measuring endometrial thickness in premenopausal patients is not a means of detecting endometrial cancer. Instead, endometrial sampling with biopsy is the way to go.