Polycystic ovarian syndrome (PCOS) is an increasingly common diagnosis among women in their reproductive years. Not only is it associated with adverse reproductive outcomes, but it also underlies a host of chronic metabolic conditions that affect long-term health. A recent review article in CMAJ explores the state of current knowledge on the diagnosis and treatment of this chronic disorder.
PCOS is diagnosed if any two of the following abnormalities are present:
- Irregular periods
- Evidence of high androgen levels, either by clinical symptoms and signs or by blood tests
- Transvaginal ultrasound (TVUS) scans showing polycystic changes in the ovary fitting PCOS criteria
The management of PCOS depends on correcting the underlying pathophysiology, whether the absence of ovulatory ovarian cycles, high androgen levels, excessive levels of insulin, or weight regulation.
Such patients will require long-term follow-up to determine the trajectory of their body mass index (BMI) and to check their blood pressure, blood sugar, blood lipids, and other metabolic markers. They are also at risk for outcomes like depression, anxiety, and obstructive sleep apnea (OSA). Diagnosis of PCOS
About 10% of females are affected by PCOS today, usually from the age of 18-39 years. Many patients go undiagnosed, however, while others are diagnosed much later.
Up to half or three-quarters of patients with PCOS are likely to have excessive body weight, reflected in a high BMI. In turn, this affects the severity of the condition. however, PCOS is only slightly more common among women with higher BMIs, indicating that obesity plays only a small role in causing this condition
PCOS is primarily caused by excessively high levels of insulin and androgens, but the sequence of events still remains unclear. The pathognomonic finding is the presence of immature follicles in the ovaries. It is possible that both hyperandrogenism and hyperinsulinemia are exacerbated by fat deposition in the body while also promoting it. This could be the result either of increased frequency of pulsatile release of gonadotropin-releasing hormone (GnRH) from the hypothalamus or of functional hyperandrogenism at adrenal or ovarian levels.
GnRH stimulates the production of both follicle stimulating hormone (FSH) and luteinizing hormone (LH), both of which increase the levels of estrogens. Estrogen, in turn, promotes follicle development in the ovary and reduces the production of FSH from the pituitary in a classical feedback loop. LH promotes androgen production within the theca granulosa cells of the ovary, with both estrogen and progesterone stimulating further LH release.
High androgen levels cause more follicles to begin developing but also stimulate their entrance into atresia, producing the classical polycystic phenotype of the ovary on TVUS.
Too much insulin may trigger increased LH levels while making more of the sex hormones available to the tissues. It could also improve the conversion of weak to strong androgens in the ovary, reducing the feedback effect of LH. Finally, it promotes fatty tissue deposition as well as an increase in the size of fat cells.
PCOS may cause a variety of changing menstrual symptoms, from irregular cycles to total anovulation, while a few women continue to have regular ovulatory periods. Some patients have a family history of PCOS, high cholesterol, high blood pressure, or diabetes.
Androgen-related symptoms range from hirsutism and acne to thinning of the hair without a receding hairline. The single symptom most closely associated with hyperandrogenism is hirsutism, and it is often the basis of beginning treatment.
The presence of violet skin striae or fat deposition in the belly region and the back of the neck may suggest Cushing syndrome or a form of congenital adrenal hyperplasia. Women with heavy bleeding or intermenstrual bleeding episodes do not typically have PCOS but should be checked for infections or uterine growths.
Thyroid issues or hyperprolactinemia are other similar-appearing conditions to be ruled out.
The Rotterdam criteria have been established to diagnose this condition, with other conditions being excluded by tests before arriving at this diagnosis. A medication review is mandatory as some may cause similar symptoms.
Androgen levels are only slightly raised in PCOS, while marked rises are more suggestive of androgen-secreting tumors. Women on combined hormonal contraception (CHC) have low androgen levels, making this test unreliable in this group.
TVUS findings of 20 or more follicles in an enlarged ovary with 1 mL or more total volume fit with a diagnosis of PCOS. Fewer follicles than this may be normal, occurring in up to a quarter of healthy women.
PCOS treatment focuses on the most distressing symptoms, whether increased bleeding, acne, hirsutism, irregular periods, or excessive weight. Losing 5-10% of body weight may help mitigate most of these symptoms but should be advised without blaming or shaming the patient for her body weight. PCOS patients are at increased risk for body image and eating disorders.
The periods may be regularized by CHC, which also relieves hirsutism and acne by reducing androgen levels. Other options for menstrual regularity include progestin-only methods, either continuous as with implants or intrauterine devices or periodically as with cyclic or rescue use of this hormone. Continuous progesterone use causes the cessation of periods.
Either of these methods also ensures endometrial protection, a top priority among women with cycles longer than 90 days, as endometrial cancer rates are increased 2-6-fold in this group.
Non-hormonal alternatives include metformin, which enhances insulin sensitivity and may help regularize cycles and reduce androgen levels as a result, accompanied by small reductions in weight. Metabolic protection is more significant among women with a BMI over 25, with androgen and insulin effects being more significant at lower BMI.
A combination of CHC and metformin may help women with a BMI over 30 and poor glucose tolerance or those who are at risk for diabetes. Inositol is a carbohydrate supplement from the vitamin B family. It is available over the counter and helps reduce the BMI and normalize cycles while possibly improving insulin sensitivity.
Anti-androgens are used to treat symptoms of hyperandrogenism, especially hirsutism, along with CHC or as an alternative to CHC when the latter cannot be used. Surgical removal of hair by laser, sometimes with the addition of topical eflornithine, is required to remove already established hair which does not respond to medical treatment. Stronger anti-androgens may be harmful to the fetus and are only used if the woman is on an effective mode of contraception.
Reproductive outcomes improve with age in the PCOS population, though women may take about two years longer than average to conceive. Over half of spontaneous pregnancies proceed to delivery, vs. nearly 75% among non-PCOS spontaneous conceptions. Among women who receive assisted reproduction technology (ART), success rates equal those among women without PCOS, at 80%.
Conservative treatments such as weight loss and metformin, inositol, or the GnRH inhibitor letrozole may be tried initially in women below 35 years, followed by more aggressive management. The latter includes laparoscopic ovarian drilling or fertility treatment.
During pregnancy, PCOS women should be monitored for miscarriage, excessive weight gain, diabetes, hypertension during pregnancy, and impaired fetal growth. Preterm delivery and Cesarean delivery are also more likely.
To mitigate the long-term risk of health complications associated with PCOS, especially with a BMI over 25, baseline and annual health evaluations are recommended. OSA is ten times more common with PCOS, while depression and anxiety risk is more than doubled.
In view of the high prevalence, serious symptoms, and important long-term consequences of PCOS, there should be an increased focus on the early diagnosis and appropriate management of this disorder.