Polycystic ovary syndrome (PCOS): Clinical sciences

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Introduction0:00–0:55

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.

Focused History and Physical0:55–2:48

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.

Lab: hCG positive2:48–3:14

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.

Lab: hCG negative3:14–7:05

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.Okay! Now let’s put it all together by assessing the criteria for PCOS.

Assess criteria for PCOS7:05–7:37

To make the diagnosis of PCOS, individuals must have any 2 out of the 3 Rotterdam criteria: ovulatory dysfunction, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound.
Additionally, other etiologies for the patient’s signs and symptoms must be excluded. If fewer than 2 PCOS criteria are present, consider an alternative diagnosis based on the patient’s presenting symptoms.

Less than 2 criteria present7:37–8:03

Examples include a genital infection as the cause of abnormal vaginal bleeding or the use of an androgenic medication that worsens acne.
Additionally, keep in mind that some facial hair patterns might be familial or genetic and not necessarily pathological.

2 or more criteria present8:03–8:51

However, if 2 or 3 criteria are present and you have excluded other etiologies, the patient has PCOS. Your next step is to assess whether or not pregnancy is desired, and to screen for commonly associated conditions, such as dyslipidemia, insulin resistance or type 2 diabetes, and metabolic syndrome.
Patients should undergo testing for diabetes and impaired glucose tolerance with a fasting glucose followed by a 2-hour glucose level after a 75-gram glucose challenge.
You can also assess cardiovascular risk by measuring BMI, fasting lipids, and metabolic syndrome risk factors. If the patient desires pregnancy, counsel the patient on recommended diet and exercise programs and advise weight loss if the patient is overweight.

Desires pregnancy8:51–10:02

Weight loss as little as 5 to 10 percent in overweight individuals can lower circulating androgen levels and result in spontaneous menses with improved pregnancy rates.
If diabetes or hypertension is present, optimize the patient’s condition preconceptionally to improve pregnancy outcomes.
Finally, if a patient has infertility due to anovulation, ovulation induction is recommended with either letrozole, but bear in mind that it’s used off label; or clomiphene citrate, to which metformin can be added in patients with obesity.
Here’s a clinical pearl! PCOS is associated with an increased risk of gestational diabetes and hypertensive disorders of pregnancy.
This risk can be further exacerbated by multiple gestation, which can be the result of ovulation induction treatment.On the other hand, if your patient doesn’t desire pregnancy, they should be counseled on recommended diet and exercise programs for cardiovascular health and weight reduction, if appropriate.

Does not desire pregnancy10:02–12:51

Weight loss improves menstrual regularity, decreases hirsutism, and reduces cardiovascular risk factors such as dyslipidemia and impaired glucose tolerance.
In addition, hormonal contraceptives can help with menstrual regularity. They also reduce the risk of endometrial cancer due to the protective effects of progestins.
Combination low-dose oral contraceptives are the primary treatment because they suppress LH levels and ovarian androgen secretion and increase circulating sex hormone-binding globulin, reducing bioavailable free testosterone.
Progestin-containing intrauterine devices, or IUDs, are also an alternative for contraception and endometrial protection.
On the other hand, hirsutism is an important and often emotionally distressing condition that affects most patients with PCOS.
Although medical treatments somewhat lessen terminal hair growth, the response is usually disappointing. Mechanical hair removal, such as shaving, waxing, electrolysis, and laser, is often the first-line method used by patients with hirsutism.
Combined oral contraceptives can result in improvement, especially when combined with spironolactone, a potassium-sparing diuretic that binds to the androgen receptor as an antagonist.
Topical eflornithine is an option for reducing hirsutism on the face, with approximately one-third of patients having clinical success.
Combination management with oral contraceptives or topical eflornithine is advised to minimize the recurrence of terminal hair growth.
Finally, patients with dyslipidemia, insulin resistance, diabetes, or metabolic syndrome should be appropriately managed with insulin-sensitizing agents, such as metformin, which is a first-line agent; or myo-inositol, which can be used as an alternative in individuals who can’t tolerate metformin.Now, one last high yield fact!
Combined oral contraceptives, although highly effective in preventing pregnancy and managing the clinical signs of PCOS, come with a risk of thromboembolism because they contain estrogen.
So they shouldn’t be recommended if your patient is over 35 with additional risk factors like hypertension or those who actively smoke; or has a past or family history of thromboembolism.Alright, as a quick recap… PCOS is diagnosed when 2 of the 3 Rotterdam criteria are met.

Review12:51–13:35

These are ovulatory dysfunction, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound.
If any 2 criteria are met and other conditions are excluded, diagnose PCOS and screen for dyslipidemia, diabetes, and metabolic syndrome.
Management is guided by the patient’s desire for pregnancy in the near future. Treatment includes diet and exercise, weight loss in overweight patients, and additional therapies directed toward the patient’s specific symptoms and
Polycystic ovary syndrome (PCOS): Video and Causes | Osmosis