What is polycystic ovary syndrome (PCOS)?

Polycystic ovary syndrome (PCOS) is a problem with the function of the ovaries and is characterized by higher levels of androgen hormones (such as testosterone), irregular menstrual cycles, and cysts on the ovaries.ⁱ It is not considered a disease. Rather, it is a syndrome that does not always have a definitive cause with symptoms that vary from person to person.ⁱⁱ

Approximately 6 to 15 percent of females have PCOS.^iii,iv Doctors may diagnose the syndrome when they note that a patient’s ovaries have more follicles developing than normal — called “polycystic ovaries.” However, females with PCOS do not always have polycystic ovaries, and individuals with polycystic ovaries do not always have PCOS.

What are the most common PCOS symptoms?

The criteria for PCOS diagnosis include lab tests showing high androgen levels, as well as issues with menstrual dysfunction, lack of ovulation or irregular ovulation, and polycystic ovaries.^v Patients do not have to have all these symptoms to be diagnosed with PCOS.

Higher levels of androgens

Females normally produce testosterone, but patients with PCOS have higher than normal levels of testosterone and related hormones called androgens. Androgens include testosterone, dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A), and dihydrotestosterone (DHT).^vi

Some common PCOS symptoms are related to elevated levels of testosterone and related male hormones, called hyperandrogenism.^vii Females with hyperandrogenism symptoms may develop physical changes that are sometimes associated with more male features, called masculinization. Here are a few examples of symptoms that can be present with hyperandrogenism:^viii

• Abnormal hair growth
• Acne
• Scalp hair loss

About 70 percent of females with PCOS experience hirsutism, also known as excess hair growth, on the upper lip, chin, and face, and body hair on the chest, back, abdomen, arms, or thighs.^ix Conversely, patients can exhibit hair loss as well, called androgenic alopecia. Females with PCOS also have a higher risk of acne; around 15 to 30 percent of females with PCOS experience acne.^x,xi

Menstrual dysfunction

Not all females with PCOS have menstrual dysfunction, which is defined as any disruption in the normal menstrual cycle, including lack of menstruation (amenorrhea), infrequent menstruation (oligomenorrhea), lack of ovulation (anovulation), or failure of the ovaries to produce enough progesterone to thicken the endometrial lining (luteal phase deficiency).^xii,xiii In fact, 30 percent of females diagnosed with PCOS have normal menstrual periods.^xiv

Research shows that up to 90 percent of females with infrequent menstruation and 30 percent of females with absent menstruation meet the criteria for PCOS.^xv But again, having irregular menstrual periods does not mean that an individual has PCOS, as there are various other causes of menstrual dysfunction. A doctor can order the appropriate diagnostic tests to help determine the cause.

Polycystic ovaries

There may be some misunderstanding related to the word “cystic” in polycystic ovary syndrome. Doctors use the term “cyst” to describe a fluid-filled sac structure. They also sometimes refer to follicles as cysts, or functional cysts, when describing normal follicle development in a menstrual cycle.^xvi The term cyst can be confusing for patients since, often, people think of cysts as abnormal or pathogenic.

When cysts develop in the ovaries, they are usually harmless and resolve on their own. Follicular cysts are not uncommon and occur when follicles fail to rupture and subsequently develop fluid inside. The exact frequency of these cysts is unclear since the majority cause no symptoms and go unnoticed.^xvii They are usually discovered incidentally during an exam for another reason. Most of these cysts resolve after a menstrual cycle or two. In rare cases, the ovarian cysts can be larger, cause significant pelvic pain, or have concerning features that require additional testing to rule out cancer.^xviii

Fertility concerns

It is estimated that over 70 percent of females with PCOS experience infertility, which is typically due to lack of ovulation, called anovulation.^xix,xx,xxi In many of these cases, there is a normal number of early ovarian follicles, but a dominant follicle fails to develop, and ovulation does not occur. Only 30 percent of females with PCOS have normal menstrual cycles. In addition, some studies suggest that females with untreated PCOS are more likely to experience a miscarriage.^xxii

Related health issues

Patients with PCOS are more likely to have insulin resistance (lack of response to insulin, which leads to elevated blood glucose levels) as well as diabetes.^xxiii PCOS is also associated with higher body mass index (BMI), higher cholesterol and triglycerides, and higher blood pressure.^xxiv However, not all patients with PCOS have these conditions. Note: These conditions are not necessary for the diagnosis of PCOS and, while associated, are not necessarily caused by PCOS.

What causes PCOS?

PCOS is likely related to both genetic make-up and a person’s environment such as lifestyle factors. Several genes have been linked to PCOS, though it is still unclear if or how the condition is passed down genetically.^xxv Nevertheless, PCOS does occur more commonly in relatives of people who have it.^xxvi

Obesity, exacerbated by diet and lack of physical activity, can worsen the symptoms of PCOS in patients already susceptible to the condition due to genetic factors; however, obesity alone is not believed to cause PCOS.^xxvii,xxviii

How is PCOS diagnosed?

To diagnose PCOS, many doctors use the following criteria, called the Rotterdam PCOS diagnostic criteria. Patients must have two or more of the following symptoms:^xxix

1. Irregular ovulation/egg release (called oligoovulation) or lack of ovulation/egg release (called anovulation)
2. Signs of elevated androgen hormones, including masculinization, or lab tests showing elevated testosterone and androgens
3. Polycystic ovaries (ovaries that have numerous benign cysts on them)

There should also be no other cause — such as another endocrine issue — that could explain these symptoms.

Androgen levels can be measured with blood tests. Ovarian cysts can be diagnosed using a transvaginal ultrasound to capture images of the uterine lining and ovaries.^xxx Most healthcare providers will also perform a pelvic exam to manually and visually assess reproductive organs for signs of abnormalities.

How does PCOS impact fertility?

Fertility challenges are quite common among females who have PCOS, but many individuals do still conceive, especially with treatment and lifestyle changes. Research has shown that up to 70 percent of patients with PCOS may experience infertility,^{xxxi,xxxii,xxxiii} commonly due to either lack of ovulation or irregular ovulation.

Some studies have shown that individuals with treated PCOS have an increased chance of twin pregnancies (or other multiples); one retrospective study showed a nine-fold increase in twin pregnancies for patients with treated PCOS.^xxxiv

If a female is found to have high androgen hormone levels, causing missed periods or other menstrual cycle problems, these issues can often be addressed to better the chances of conceiving.

What are some PCOS treatments and how successful are they?

PCOS treatment options vary depending on the patient’s symptoms, medical history, and exam results. Treatments can also vary depending on whether or not an individual is trying to conceive.

PCOS treatment for patients not currently trying to conceive

The first line of treatment for patients with PCOS who do not wish to conceive is a regimen of combined hormonal oral contraceptives (birth control pills).^xxxv The combination of estrogen and progesterone in the pills causes the brain to produce less luteinizing hormone (LH) and less stimulation of the ovaries to produce excess androgens. Thus, the amount of testosterone and other androgen hormones in the bloodstream is reduced.

Treatment with hormonal birth control pills is often successful at reducing the hirsutism and hair loss associated with PCOS. Antiandrogen medications (such as spironolactone) can also be added if there is no improvement in these symptoms after six months on oral contraceptives.^xxxvi

The drug metformin (brand names Glucophage^®, Riomet^®, Glumetza^®) is a medication that is typically used to treat diabetes, but it has also been used to treat PCOS symptoms as it has been shown to help relieve symptoms of insulin resistance.^xxxvii

PCOS treatment for women trying to conceive and struggling with infertility

Losing weight is the first-line therapy for the management of infertility related to PCOS in patients who are also overweight or obese.^xxxviii The reason is females with higher BMI are more likely to have irregular ovulation or lack of ovulation if they have PCOS; thus, they have a higher incidence of infertility.^xxxix Bariatric (weight loss) surgery, such as gastric bypass or a gastric sleeve, improves the regularity of menstrual cycles and increases both ovulation and conception rate.^xl

Letrozole (brand name Femara^®) is considered the first-line medication for stimulating ovulation in PCOS, despite it being used off-label (meaning it is not FDA-approved for this purpose but may still be used). Clomiphene citrate (brand names Clomid^®, Serophene^®) is another medication that is often recommended to stimulate ovulation in patients with PCOS.^xli,xlii Evidence suggests that up to 75 percent of patients with PCOS will ovulate after administration of clomiphene, and a meta-analysis showed that clinical pregnancy rate was increased up to five-fold in PCOS patients using clomiphene compared to no treatment.

When comparing the two, letrozole is considered as effective as clomiphene or potentially more effective.^xliii,xliv The choice between clomiphine and letrozole may depend on the side effects that a particular patient experiences. One large study showed that the most common side effect with clomiphene was hot flashes, while it was fatigue and dizziness with letrozole.^xlv,xlvi

Doctors may recommend in vitro fertilization (IVF) to patients with PCOS if they have other infertility factors such as blocked tubes, endometriosis, another genetic diagnosis, or male factor infertility, or if medication to stimulate ovulation doesn’t help. Patients with PCOS undergoing IVF have similar success rates as other IVF patients; PCOS does not seem to reduce the success of IVF. The success rate of IVF in females with PCOS is between 30 and 40 percent per cycle.^xlvii

Other risks or concerns with PCOS

PCOS affects the body in a number of ways, such that females with PCOS may have greater risks of other conditions.

Endometrial cancer

The risk of endometrial cancer is heightened 2.7-fold for females with PCOS.^xlviii Therefore, endometrial biopsy or ultrasound may be recommended to rule it out. In addition, there may be a heightened risk of ovarian cancer with PCOS, though the use of oral contraceptive pills may reduce some of that higher risk.^xlix Contrary to popular perception, there is no known association between PCOS and breast cancer.

Cardiovascular disease

Patients with PCOS have a higher chance than other females of developing cardiovascular disease, and some evidence suggests risks may be higher for individuals in their 30s and 40s.^l This heightened risk may be related to other effects of PCOS. For example, PCOS can lead to metabolic syndrome, which has a detrimental effect on the cardiovascular system and may contribute to heart disease.^li

Diabetes

A PCOS diagnosis may mean that the patient has a higher likelihood of diabetes, even though the link is not fully understood. Lifestyle changes, including losing weight and following a healthy diet, may lower this risk.

Conclusion

PCOS can be a challenging condition for individuals trying to conceive. Irregular menstrual periods and abnormal androgen levels can interfere with fertility, but females with PCOS may see improvements in their condition with lifestyle changes such as following a healthy diet, losing weight, or monitoring blood sugar levels.

Outside of challenges with fertility, individuals with a PCOS diagnosis should work with their primary healthcare provider to monitor for any other health issues, such as insulin resistance and heart disease, that may arise.