Is hirsutism always secondary to PCOS?

Hirsutism is growth of excess hair with an androgen-mediated male-pattern distribution. This condition affects up to 8% of all women. Hypertrichosis generally refers to excessive body hair. To evaluate the degree and extent of a patient’s body-hair growth, a modification of the Ferriman-Gallwey scale is used.

Hirsutism can be idiopathic or a manifestation of a hyperandrogenic state. The differential diagnosis for pathologic causes of hirsutism includes adrenal and ovarian etiologies and insulin resistance. Other causes of elevated plasma androgens are malignancies, systemic diseases resulting in insulin resistance, endocrine abnormalities, and medications.The extent of hair growth in women is genetically and racially determined. This makes evaluation of hirsutism difficult.


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Women who have hirsutism in the absence of androgen excess and presence of regular menses and ovulation are defined as having idiopathic hirsutism.Hyperthecosis is another ovarian cause of hyperandrogenism. In this condition, androgen excess is the result of luteinized theca cells that are present throughout the ovarian tissue. This overproduction of androgens by the ovaries is not limited to the reproductive years.

The adrenal causes of hirsutism include congenital adrenal hyperplasia and adrenal tumors, most commonly adrenal carcinomas. Some patients with adrenal tumors present with both hirsutism and signs and symptoms of Cushing’s syndrome since some adrenal tumors overproduce cortisol as well as androgens. Generally speaking, Cushing’s syndrome, metabolic syndrome, and insulin resistance can also result in some degree of hirsutism.

The differential diagnosis of hyperandrogenism includes gestational hyperandrogenism, which can result from either adrenal or ovarian tumors or ovarian cysts that produce androgens. This condition presents as a sudden increase in male-pattern hair growth or other signs and symptoms of virilization, including male-pattern baldness, acne, voice change, or cliteromegaly during pregnancy. A pregnant woman who presents with sudden symptoms of hyperandrogenism should be carefully and extensively evaluated since a malignant tumor may be the source of excess androgens.

There are three additional causes of hirsutism that are not directly related to the elevation of plasma androgens: Mild elevation of prolactin levels, severe insulin resistance, and thyroid disease. In a patient with severe insulin resistance, hirsutism is the result of ovarian stimulation by insulin, which results in overproduction of ovarian androgens.

Prolactin-mediated hirsutism is caused by an alteration of the gonadotropin-releasing hormone pulse generator leading to hypogonadotropic hypogonadism. Elevation of plasma prolactin levels, however, can be either benign or an indication of other potentially serious problems, such as pituitary diseases (including pituitary tumors).

Differential diagnosis of amenorrhea

A common manifestation of PCOS, amenorrhea can be categorized as primary or secondary and falls into one of two classifications. One classification describes primary amenorrhea as a direct result of ovarian dysfunction, whereas secondary amenorrhea refers to lack of menses due to a wide range of endocrine abnormalities, including pituitary and hypothalamic diseases and genetic abnormalities.

In the obstetrics/gynecology literature, however, primary amenorrhea is defined as absence of menses by age 16 in females with other secondary sexual characteristics. Secondary amenorrhea is defined as lack of menses for at least three cycles or six months in women who had previously had menstrual cycles. PCOS is one of the secondary causes of amenorrhea. (The most common cause is pregnancy.) Additional causes include the endocrine dysfunctions mentioned previously.

Oligomenorrhea refers to irregular menses. Like secondary amenorrhea, it can be caused by a number of endocrine abnormalities. Both conditions can be accompanied by anovulation and the resulting infertility.

The relationship between insulin resistance and PCOS

There is a well-established relationship between elevated plasma levels of insulin and androgens, obesity, and PCOS. Insulin is known to affect the lipid profile and cause androgenic effects. Patients with PCOS have been shown to be at much higher risk for developing diabetes and therefore at a higher risk for abnormal lipid metabolism and cardiovascular disease. Consequently, patients suspected of having PCOS should be evaluated for disturbances in glucose metabolism.

Differential diagnosis of obesity

Obesity is defined by the CDC as BMI ≥30, whereas individuals with BMI between 25 and 30 are classified as overweight. The differential diagnosis of obesity is extensive and includes poor diet, lack of exercise, sleep disorders, psychological problems, medications, genetic factors, and endocrine abnormalities.

The endocrine causes of obesity are largely type 2 diabetes, insulin resistance, hypothyroidism, Cushing’s syndrome, and PCOS. The obesity resulting from the latter two shows a central distribution of the body weight and increased visceral fat similar to that seen in patients with insulin resistance or metabolic syndrome.

The relationship between obesity and PCOS

Obesity, especially central obesity, is a relatively common symptom of both PCOS and insulin resistance. A study of 1,741 patients with PCOS found that 35%-60% were obese. Frequently, even nonobese PCOS patients suffer from an androgen-mediated abnormal fat distribution to the trunk despite BMI in the normal range.

How should a person suspected of having PCOS be evaluated?

A history and physical examination is always crucial and should include a complete family history and review of systems. Measure BP, BMI, and waist-hip ratio, and check for signs of hyperandrogenism or insulin-resistance stigmata. The goal is to decipher any other endocrine, systemic, or hereditary diseases that may cause similar presenting signs and symptoms.

Laboratory examination should include total and free testosterone, thyroid-stimulating hormone, prolactin, fasting lipid-risk profile, and a glucose tolerance test. Consider a pelvic ultrasound, gonadotropic evaluation, fasting insulin levels, and 24-hour urinary free cortisol (to rule out Cushing’s). A pregnancy test should be ordered for patients complaining of amenorrhea. The evaluation should serve as the initial step of referring the patient to an endocrinologist or obstetrician/gynecologist for further evaluation and initiation of proper treatment.

Treatment options

Management of PCOS does not comprise treating the condition as a whole but rather treating the individual signs and symptoms. Even if therapy is conducted in the primary-care setting, any woman suspected of having PCOS should be evaluated by an endocrinologist or a gynecologist.

Obesity treatment is crucial. Data show improvements in both the hyperandrogenic state (as witnessed by an increase in the rate of spontaneous pregnancies) and hyperinsulinemic state (as a result of weight loss). Diet and lifestyle modifications should be encouraged regardless of other treatments being utilized.

Patients suffering from insulin resistance and/or type 2 diabetes (with or without PCOS association) should be prescribed metformin. Metformin has also been shown to be effective in treating PCOS patients. In obese women with PCOS, metformin has been shown to improve regulation of menses and ovulation, as witnessed by an increase in number of spontaneous pregnancies. The combination of weight loss and insulin-resistance treatment with metformin can also contribute to a reduction in male-pattern hair growth. There is some evidence of beneficial and synergistic effects of metformin added to lifestyle modifications, but there does not seem to be a solid consensus in the literature. Patients with type 2 diabetes (regardless of comorbid PCOS) may be prescribed thiazolidinediones. However, use of these drugs in nondiabetic PCOS patients is not currently recommended.

Irregular menses are best controlled with oral contraceptives, which effectively reduce the production of ovarian androgens and regulate menstrual cycles. Decreasing the amount of plasma androgens can also relieve hirsutism and, perhaps, acne.

The simplest way for women to remove unwanted hair is through the use of depilatory agents or by shaving. Antiandrogenics, such as spironolactone, finasteride, and cyproterone acetate, can also be used. The latest treatment option is eflornithine (Vaniqa) cream.

Outlook

PCOS is a syndrome—not a disease—and, as such, cannot have a prognosis. The long-term health outcome of patients with PCOS depends on management of its complications, including diabetes, glucose intolerance, and insulin resistance. Patient education is an important part of managing PCOS and should not be overlooked.

Dr. Aliabadi is associate professor of biomedical sciences and physician assistant studies at the University of South Alabama College of Allied Health Professions in Mobile. Dr. Warner is associate professor of internal medicine, family practice, and physician assistant studies at the University of South Alabama College of Medicine, also in Mobile.