Polycystic Ovary Syndrome: a Review (Ricardo Azizz)

Polycystic Ovary Syndrome (PCOS) is an important condition that all health practitioners
who see women should be completely familiar with. It is not benign. Infertility, acne, irregular
cycles, insulin resistance, and excess body hair growth are some of the most common features
that plague women with PCOS. Moreover, PCOS is a relatively common diagnosis. It is
estimated that between 5 and 20% of women suffer from it. Despite this, “one third of women
report greater than 2 years or three or greater health professionals before” diagnosis.1
What is PCOS?
PCOS is the “single most common endocrine-metabolic disorder in reproductive-aged
women.”1 Because of the complex nature of endocrine disorders, there are many potential
features of PCOS. While the presentation may differ among women, there are 3 main clinical
findings: hyperandrogenism, anovulatory cycles, and polycystic ovaries. Per the Rotterdam
criteria, two of these findings are required to make a diagnosis of PCOS.
Clinical hyperandrogenism can take the form of excess male pattern terminal hair growth
(also known as hirsutism), acne, and alopecia. Hyperandrogenism can also be diagnosed with
“one abnormal androgen value,” such as elevated testosterone or DHEA-S.1 Abnormal,
frequently anovulatory, cycles are another mainstay of PCOS presentation. Oligo-anovulation is
a commonly used term that refers to cycles longer than 35 days. Because of this, many women
will have less than 8-10 cycles per year. Some women present with more frequent menstrual
bleeding days each cycle. The final diagnostic criterion is polycystic ovarian morphology.
Ultrasound is most useful after a patient has been off of hormonal suppression, such as oral
contraceptives (OCPs), for at least 6 months. This criterion is less useful in adolescents.
Why PCOS is important.
In addition to its prevalence, PCOS is an important condition because of a multitude of
factors. Regarding the diagnostic criteria, the sequelae of hyperandrogenism contribute to quality
of life impairment and cycle abnormalities contributes to infertility. Obesity is another factor in
PCOS that contributes to its decreased quality of life. Patients that present with PCOS are more
likely to be obese, but the actual difference in weight between matched populations without
PCOS may not be significant, at least in United States. Importantly, when patients are matched to
the rest of the population for factors including obesity and age, women with PCOS are
significantly more likely to have diabetes mellitus. Both insulin resistance and decreased insulin
production are believed to contribute to this. This significant predisposition for diabetes also
increases the risk for metabolic syndrome, which brings about its own potential (albeit poorly
researched) risks, including cardiovascular disease and non-alcoholic fatty liver disease. Separate
from metabolic syndrome, women with PCOS are still at greater risk for hypertension. Finally,
when women with PCOS are able to achieve pregnancy, they are at increased risk for gestational
diabetes, macrosomia, and pregnancy related hypertension.
Workup of PCOS.
The diagnosis of PCOS must be confirmed by the Rotterdam Criteria and by exclusion of
other diseases. To accomplish this, a thorough physical should be used to identify hair growth,
acne, obesity, and virilization. Additionally, the thyroid should be inspected. Transvaginal
ultrasound can be used to evaluate the ovaries and endometrial thickness after diagnosis. It can
also be used to evaluate for polycystic ovarian morphology to make a diagnosis. Practitioners
must recall that ultrasound is not necessary for diagnosis if the other Rotterdam criteria have
been satisfied.
 Hormone testing has value in diagnosis as well as treatment planning. To verify ovulation
or evaluate anovulatory cycles, progesterone can be measured on days 22-24 of their cycle. In
women who are able to track their cycles and fertile signs, a more targeted approach can use
post-peak days to measure progesterone. Practitioners should also consider measuring anti-
müllerian hormone (AMH), a thyroid panel, prolactin, follicular 17-hydroxyprogesterone (17-
OH), 24-hour urine free cortisol, testosterone, DHEA-S, LH, and FSH.2 If the patient is using
hormonal contraception or therapy, it is recommended that hormone levels be measured after 6
months off of medication. Elevated AMH suggests increased preantral follicles and elevated 17-
OH suggests nonclassic adrenal insufficiency, the most common autosomal-recessive disorder.
Cortisol testing is useful to rule out Cushing’s, as many patients may share similar clinical
presentations.
In women diagnosed with PCOS, testing should be pursued for some comorbidities. A 2-
hour, 75g fasting oral glucose tolerance test (OGTT) is recommended to rule out diabetes
because hemoglobin A1C is not a reliable marker in PCOS. Azziz also recommends a lipid
profile and LFTs at diagnosis in all patients. Additionally, OGTT and lipids be repeated every 2-
3 years.1
Lastly, all of these patients should be screened for anxiety and depression due to the
adverse effects of PCOS symptoms on quality of life.
Treatment Principles
The goals of PCOS management are multifocal: decrease androgen presence and action,
regulate menstrual cycles and therefore protect the endometrium, address metabolic concerns,
and improve fertility. For women not desiring pregnancy, the traditional first-line therapy is
combination OCPs. These serve to provide regular menses and protect the endometrium from
unfettered proliferation associated with anovulatory cycles. They also “suppress gonadotropin
secretion and ovarian androgen production.”1 Patients desiring fertility or opposed to
contraceptive use can use cyclic bioidentical progesterone during the luteal phase, which is
available PO, PV, or IM. This serves to regulate cycles and prevent endometrial overgrowth. In
these cases, the patient can use metformin to increase insulin sensitivity and therefore decrease
circulating androgens secondary to the complex endocrine-metabolic nature of this syndrome.
Regardless of primary treatment method, patients should attempt to decrease androgens
by weight loss.3 Practitioners can suggest a low carbohydrate diet, calorie restriction, and
increased activity to accomplish this. Other methods of addressing hyperandrogenism include
spironolactone and flutamide. Patients with very resistant hyperandrogenism may need to
consider using gonadotropin-releasing agonists.
Ovulation induction will be required in some patients, using either clomiphene or
letrozole. Failure of these methods often leads to recommendation of ovarian drilling or in-vitro
fertilization with embryo transfer. While not in mainstream of therapy, a number of providers
report success using cycle charting and fertility awareness-based methods (FABMs) to cooperate
with medical therapy. By using temperature, hormone test strips, and/or cervical mucus models,
patients are able to identify whether or not their cycles are truly within normal limits. This
proves valuable, as 40% of hirsute women who claim to be eumenorrheic are actually oligo-
anovulatory. Cycle tracking can also identify the follicular phase and luteal phase accurately so
one can ideally use or measure progesterone on specific post-ovulatory luteal days, as opposed to
numbered cycle days in women who do not use FABMs. Unlike other treatment methods,
FABMs with cooperative medical management allow a woman to simultaneous delay pregnancy
and treat her symptoms while she restores her fertility. While OCPs provide symptomatic relief,
they do not work to restore fertility.

[1] Azziz, R. (2018). Polycystic Ovary Syndrome. Obstetrics & Gynecology, 132(2), 321-336.

doi:10.1097/aog.0000000000002698
[2] Sheehan, M. T. (2004). Polycystic Ovarian Syndrome: Diagnosis and Management. Clinical
Medicine & Research, 2(1), 13-27. doi:10.3121/cmr.2.1.13
[3] Dokras, A., Sarwer, D. B., Allison, K. C., Milman, L., Kris-Etherton, P. M., Kunselman, A.
R., . . . Legro, R. S. (2016). Weight Loss and Lowering Androgens Predict Improvements in
Health-Related Quality of Life in Women With PCOS. The Journal of Clinical Endocrinology &
Metabolism, 101(8), 2966-2974. doi:10.1210/jc.2016-1896