What is polycystic ovary syndrome (PCOS)?

PCOS is a problem with the function of the ovaries and is characterized by elevations in androgens (e.g., testosterone), irregular menstrual cycles, and cysts on the ovaries.ⁱ

PCOS may be diagnosed when the ovaries have more follicles developing than normal (“polycystic ovaries,” PCO); however, this is not always present. PCOS is not considered a disease but rather a syndrome, as it does not always have a definitive cause and is characterized by a varied set of symptoms.ⁱⁱ Women with PCOS do not always have PCO, and those with PCO do not always have PCOS.

Androgens are testosterone and hormones related to testosterone, including dehydroepiandrosterone sulfate [DHEAS], dehydroepiandrosterone [DHEA], androstenedione [A], and dihydrotestosterone (DHT).ⁱⁱⁱ Women without PCOS do make testosterone, but in PCOS there are higher than normal levels of testosterone and related hormones.

Approximately 6-15 percent of women suffer from PCOS, with reported frequency varying depending on the diagnostic criteria utilized.^iv,v The criteria for diagnosis include laboratory evidence of excess androgens, menstrual dysfunction, lack of ovulation or irregular ovulation, and polycystic ovaries.^vi

Menstrual dysfunction is any disruption in the normal menstrual cycle including lack of menstruation (amenorrhea), infrequent menstruation (oligomenorrhea), lack of ovulation (anovulation), or failure of ovaries to produce enough progesterone to thicken the endometrial lining (luteal phase deficiency).^vii,viii  

Patients do not have to have all these symptoms to be diagnosed with PCOS. In fact, 30 percent of women diagnosed with PCOS have normal periods.^ix Research shows that up to 90 percent of women with infrequent menstruation and 30 percent of women with absent menstruation meet the criteria for PCOS.^x  The flipside to this is that having menstrual dysfunction does not mean that an individual has PCOS, as there are various other causes of menstrual dysfunction.  A clinician would order the appropriate diagnostic tests to help distinguish the cause.  

Women with PCOS are more likely to have insulin resistance (lack of response to insulin which leads to elevated glucose in the blood) as well as diabetes.^xi PCOS is also associated with elevated body mass index (BMI), elevated lipids (triglycerides and cholesterol, fats in the body), and high blood pressure.^xii However, not all patients with PCOS have these conditions.

‍

What are the most common PCOS symptoms?

There are some common symptoms related to the elevated levels of testosterone and related male hormones or hyperandrogenism.^xiii Women with hyperandrogenism symptoms may develop physical changes, which are sometimes associated with more male features. A few examples of other symptoms that can be present with hyperandrogenism include:^xiv

• Abnormal hair growth
• Acne
• Hair loss  

About 70 percent of women with PCOS experience hirsutism, also known as excess hair growth, on the upper lip, chin, and face, but also body hair on the chest, back, abdomen, arms, or thighs.^xv Conversely, patients can exhibit hair loss as well (androgenic alopecia). In addition, women with PCOS have a higher risk of experiencing issues with acne, with around 15 to 30 percent of women with PCOS having acne.^xvi,xvii

It is estimated that over 70 percent of women with PCOS suffer from infertility, which is typically from anovulation.^xviii, ^xix, ^xx 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 women with PCOS have normal menses. In addition, some studies suggest that women with untreated PCOS are more likely to experience a miscarriage.^xxi

As stated above, PCOS is often associated with metabolic issues such as diabetes, increased abdominal girth/elevated BMI, elevated lipid levels, and hypertension. These conditions are not necessary for the diagnosis of PCOS and, while associated, are not necessarily a direct manifestation of the syndrome.

‍

What causes PCOS?

PCOS is related to both genetic make-up and a person’s environment (such as lifestyle factors).

Several genes have been linked to PCOS, meaning that a woman’s genetic make-up likely contributes to the development of PCOS.^xxii It is unclear which genes are responsible for PCOS and it is not clear exactly if or how the condition is passed down genetically. Nevertheless, PCOS does occur more commonly in relatives of affected patients.^xxiii

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

‍

How is PCOS diagnosed?

In order to diagnose PCOS, many physicians use the following criteria (Rotterdam PCOS diagnostic criteria):  

Patients must have two out of the three of:^xxvi

1. Oligo-ovulation and/or anovulation (irregular or lack of ovulation or egg release)

2. Clinical or biochemical signs of elevated androgens, including masculinization or elevated male hormones such as testosterone and similar hormones

3. Polycystic ovaries (ovaries that have numerous benign cysts on them)

There should also be no other explanation—such as another endocrine issue—that can explain these findings.

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.^xxvii Most healthcare providers will also perform a pelvic exam to manually and visually assess reproductive organs for signs of abnormalities.

What are cysts?

There may be some misunderstanding related to the “cystic” term in “polycystic ovary syndrome”. The term cyst is used clinically to describe a fluid-filled sac structure. Follicles are sometimes referred to as cysts, or functional cysts, and can describe normal follicle development in a menstrual cycle.^xxviii The term cyst can also be confusing for patients since often people think of cysts as abnormal or pathogenic.  

When a cyst does develop in the ovary, 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 not known since the majority cause no symptoms and go unnoticed.^xxix They are usually discovered incidentally on examination for another reason. Most of these cysts resolve after a cycle or two. In rare cases, the cyst can be larger, cause significant pelvic pain, or have features concerning for malignancy that require additional workup.^xxx

‍

How does PCOS impact fertility?

Female infertility is quite common among women who have PCOS, but many women do still conceive, especially with treatment and lifestyle changes. Research has shown that up to 70 percent of patients with PCOS may suffer from infertility.^{xxxi,xxxii,xxxiii}  This is commonly due to either anovulation 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 those with treated PCOS. ^xxxiv,xxxv

If a woman is found to have high male 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 treatments after diagnosis can vary depending on the symptoms, medical history, and what is determined during a physical exam. Treatments can also vary depending on whether or not a woman 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).^xxxvi The combination of estrogen and progesterone has a negative signaling effect on the brain, which then produces less luteinizing hormone (LH) and therefore less stimulation of the ovarian production of excess androgens. This reduces the amount of testosterone and other male hormones in the bloodstream.

With antiandrogen symptoms (hirsutism, acne, hair loss), treatment with oral contraceptive 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.^xxxvii

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

PCOS treatment for women trying to conceive and struggling with infertility

Weight loss is the first-line therapy for the management of infertility related to PCOS in patients who are also overweight or obese.^xxxix This is because women with higher BMI are more likely to have anovulation and oligovulation if they have PCOS and thus a higher incidence of infertility.^xl Bariatric (weight loss) surgery, such as gastric bypass or a gastric sleeve, improves the regularity of menstrual cycles and increases both ovulation as well as the subsequent rate of conception.^xli

Letrozole (Femara®) is considered first-line medication for ovulation induction in PCOS, despite it being used off-label (i.e., it is not FDA-approved for this purpose but may be used as such).  It is considered as effective as clomiphene^xlii, or potentially more effective. ^xliii 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®. ^xliv,xlv

Clomiphene citrate (brand names Clomid®, Serophene®) is another medication that is often recommended for ovulation induction (stimulation of ovulation) in patients with PCOS.^xlvi,xlvii Evidence suggests that up to 75 percent of patients with PCOS will ovulate after administration of clomiphene^xlviii and a meta-analysis showed that clinical pregnancy rate was increased up to 5-fold in PCOS patients using clomiphene compared to no treatment.^xlix

In vitro fertilization (IVF) may be used in patients with PCOS if there are other infertility factors (such as blocked tubes, endometriosis, another genetic diagnosis, or male factor infertility) or if ovulation induction fails. Patients with PCOS undergoing IVF have similar success rates as patients undergoing IVF for blocked tubes; PCOS does not seem to reduce the success of IVF. The success rate of IVF in women with PCOS is between 30 and 40 percent per cycle.^l

‍

Other risks or concerns with PCOS

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

The risks of endometrial cancer are heightened 2.7-fold for women with PCOS.^li Therefore, endometrial surveillance via a biopsy or ultrasound may be recommended. In addition, there may be a heightened risk of ovarian cancer with PCOS, though the use of oral contraceptive pills may mitigate some of those risks.^lii Contrary to popular perception, there is no known association between PCOS and breast cancer.

Women with PCOS have a higher risk than other women for cardiovascular disease, and some evidence suggests risks may be higher for women in their 30s and 40s.^liii This heightened risk may be related to other risk factors associated with PCOS. For example, PCOS can lead to metabolic syndrome, which has a detrimental effect on the cardiovascular system and may contribute to heart disease.^liv

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

‍

Conclusion

PCOS can be a challenging condition when trying to conceive but can also be of concern for other reasons.

Outside of challenges with fertility, those with a PCOS diagnosis should work with health professionals and their primary health care provider to monitor whether any other health issues may arise. Of primary concern are heart disease and insulin resistance.

And while irregular menstrual periods and abnormal androgen levels can interfere with fertility, women with PCOS may see improvements in their condition with lifestyle changes such as losing weight, following a healthy diet, or monitoring blood sugar levels.