New review aims to help clinicians diagnose and manage PCOS

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Polycystic ovary syndrome (PCOS) is an increasingly common diagnosis among women in their reproductive years. Not only is it associated with adverse reproductive outcomes, it also underlies many chronic metabolic conditions that affect long-term health. A recent review article CMAJ Explores the current state of knowledge about the diagnosis and treatment of this chronic disorder.

Study: Diagnosis and Management of Polycystic Ovarian Syndrome.  Image credit: Kateryna Kon/Shutterstock.com
Study: Diagnosis and management of polycystic ovarian syndrome. Image credit: Kateryna Kon/Shutterstock.com

Background

PCOS is diagnosed when two of the following abnormalities are present:

  • Irregular periods
  • Evidence of high androgen levels, either by clinical signs and symptoms or by blood tests
  • Transvaginal ultrasound (TVUS) scans show polycystic changes in the ovaries fitting PCOS criteria.

Management of PCOS depends on correcting the underlying pathophysiology, absence of ovulatory ovarian cycles, high androgen levels, excessive insulin levels, or weight control.

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 such as depression, anxiety and obstructive sleep apnea (OSA). PCOS diagnosis

About 10% of women today are affected by PCOS, usually from the ages of 18-39. Many patients go undiagnosed, but others are diagnosed much later.

Half or three-quarters of patients with PCOS are likely to be overweight, which is reflected in a high BMI. Instead, it affects the severity of the condition. However, PCOS is slightly more common in women with a higher BMI, indicating that obesity plays a minor role in causing the condition.

PCOS is primarily caused by excessively high levels of insulin and androgens, but the sequence of events remains unclear. The presence of immature follicles in the ovary is a pathognomonic finding. It is possible that both hyperandrogenism and hyperinsulinemia increase and promote body fat accumulation. This may be the result of increased frequency of pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus or functional hyperandrogenism at the adrenal or ovarian level.

GnRH stimulates the production of both follicle stimulating hormone (FSH) and luteinizing hormone (LH), both of which increase estrogen levels. Estrogen, in turn, stimulates follicle development in the ovary and reduces the production of FSH from the pituitary in a classical feedback loop. LH stimulates androgen production in ovarian theca granulosa cells, while both estrogen and progesterone stimulate LH release.

High androgen levels start to produce more follicles but this stimulates their entry into atresia, producing the classical polycystic phenotype of the ovary on TVUS.

Too much insulin can increase LH levels while making more sex hormones available to the tissues. It may also enhance the conversion of weaker to stronger androgens in the ovary, reducing the effect of the LH response. Finally, it promotes the accumulation of fatty tissue as well as the growth of fat cells.

PCOS symptoms

PCOS can cause a variety of variable menstrual symptoms, from irregular cycles to complete anovulation, while some women continue to ovulate regularly. 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 hair. The single symptom most closely associated with hyperandrogenism is hirsutism and is often the basis of initial treatment.

The presence of purple skin striae or fatty deposits in the abdominal region and back of the neck may suggest a form of Cushing’s syndrome or congenital adrenal hyperplasia. Women with heavy bleeding or menstrual bleeding usually do not have PCOS but should be tested for infection or uterine enlargement.

Thyroid problems or hyperprolactinemia are other similar-appearing conditions that can be ruled out.

PCOS diagnosis

The Rotterdam criteria for this diagnosis have been established, excluding other conditions through testing before reaching this diagnosis. A medication review is mandatory because some can cause similar symptoms.

Androgen levels are mildly elevated in PCOS, while marked elevations are more indicative of androgen-secreting tumors. Women on combined hormonal contraceptives (CHC) have lower androgen levels, making this test unreliable in this group.

TVUS results of 20 or more follicles in an enlarged ovary with a total volume of 1 ml or more are associated with a diagnosis of PCOS. Fewer follicles than this may be normal, occurring in a quarter of healthy women.

Management of PCOS

PCOS treatment focuses on the most distressing symptoms, such as increased bleeding, acne, hirsutism, irregular periods or excess weight. Losing 5-10% of body weight can help alleviate most of these symptoms but the patient should be advised not to blame or shame his body weight. PCOS patients are at increased risk for body image and eating disorders.

Periods can be regularized by CHC, which relieves hirsutism and acne by reducing androgen levels. Other options for menstrual regularity include progestin-only regimens, either continuously such as implants or intrauterine devices, or intermittently with cyclic or rescue of these hormones. Continuous use of progesterone stops periods.

Either of these methods also ensures endometrial protection, a top priority in women with cycles longer than 90 days, as endometrial cancer rates increase 2-6-fold in this group.

Non-hormone options include metformin, which increases insulin sensitivity and can help regulate cycles and consequently lower androgen levels, leading to weight loss. Metabolic protection is more significant in women with a BMI greater than 25, with androgen and insulin effects more significant at lower BMIs.

A combination of CHC and metformin may help women with a BMI greater than 30 and poor glucose tolerance or at risk for diabetes. Inositol is a carbohydrate supplement in the B vitamin family. It is available over the counter and may help reduce BMI and normalize cycles while 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 hair removal by laser, sometimes with the addition of topical aflonithin, is required to remove already established hair that does not respond to medical treatment. Strong anti-androgens can be harmful to the fetus and are used only as effective methods of contraception in women.

Reproductive outcomes improve with age in the PCOS population, although women may take about two years longer than average to conceive. More than half of spontaneous pregnancies proceed to delivery, vs. About 75% of non-PCOS conceptions are spontaneous. For women who receive assisted reproductive technology (ART), the success rate is as high as 80% for women without PCOS.

Weight loss and conservative treatment such as metformin, inositol, or the GnRH inhibitor letrozole may be tried initially in women younger than 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, gestational hypertension and impaired fetal growth. Preterm delivery and cesarean delivery are also more likely.

To reduce the long-term risk of health complications associated with PCOS, especially if BMI is greater than 25, baseline and annual health assessments are recommended. OSA is ten times more common with PCOS, while the risk of depression and anxiety more than doubles.

Conclusion

Given the high prevalence, severe symptoms, and significant long-term consequences of PCOS, more attention should be paid to early diagnosis and appropriate management of this disorder.



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