Polycystic ovary syndrome is one of the most common endocrinopathies in women during reproductive years. It is a complex disease process that leads to ovulatory dysfunction, infertility, irregular uterine bleeding, and various skin manifestations. The skin manifestations include hirsutism, oily skin, acneiform eruptions, and skin pigmentation known as achanthosis nigricans.¹

There are certain manifestations of the polycystic ovary syndrome that also affect the health of women; one of these is obesity, which is present in about 30%–50% of patients with polycystic ovary syndrome. This will predispose women to what is known as metabolic syndrome. This metabolic syndrome includes prediabetes, diabetes, and hypertension.² Furthermore, there is the possibility for these patients to develop endometrial cancer if they are not treated properly.

The etiology of polycystic ovary syndrome is not known, but it may be due to some genetic predisposition. Polycystic ovary syndrome is reported to be present in 50% of sisters and 40% of mothers of patients with this disease process. The mode of inheritance is suggested to be autosomal or X-linked process. Aneuploides and polyploides of the X chromosome have been described. Deletion of the long arm of chromosome 11 was seen in some cases of polycystic ovary syndrome. The genes related to steroidogenesis and carbohydrate metabolism are suggested to be factors in the development of this syndrome.^3,4

Polycystic ovary syndrome was first described in 1935 by Irving Stein and Michael Leventhal.⁵ These two gynecologists from Chicago described a category of women with enlarged ovaries, irregular cycles, and infertility. The ovaries contained multiple cysts, which are follicles that have not ovulated. They treated these women with wedge resection of the ovaries; the women resumed ovulatory cycles, and some of them achieved pregnancy.⁶ Stein-Leventhal syndrome remained the characteristic identification of this disease because of these two scientists and their contribution. Wedge resection was the main line of treatment in these patients until the late 1970s. At that time, endocrine science was not advanced, and hormonal assays, as we know today, were not present or available. Therefore, the Stein-Leventhal syndrome was a purely clinical and morphological diagnosis. In the mid-1970s, it became possible, due to the development of proper hormonal assays, to evaluate patients’ gonadal hormones. Several societies developed criteria based on endocrine testing to rule out other diseases.

Diagnostic criteria were put forward by several societies and institutions. In the early 1990s, the National Institutes of Health (NIH) had a consensus meeting; afterward, certain criteria were published as diagnostic for patients with polycystic ovary syndrome⁷:

1. 
   

   Anovulation, manifested by oligomenorrhea or amenorrhea

   
   
2. 
   

   Excess androgen activity, manifested by hyperandogenemia or hypoandrogenism

Patients who fulfilled these two criteria would be diagnosed as having polycystic ovary syndrome.

In 2003, representatives of the American Society of Reproductive Medicine and the European Society of Human Reproduction and Embryology met in Rotterdam, the Netherlands, and developed the Rotterdam criteria for the diagnosis of polycystic ovary syndrome^8,9:

1. 
   

   Amenorrhea/oligomenorrhea

   
   
2. 
   

   Hyperandrogenism/hyperandrogenemia

   
   
3. 
   

   Polycystic appearance of the ovary on ultrasound

Two of the 3 criteria must be present for the diagnosis of polycystic ovary syndrome.

In 2006, the Androgen Excess Society met and published their criteria, which are similar to the Rotterdam criteria for the diagnosis of polycystic ovary syndrome.¹⁰

The hypothalamic-pituitary-ovarian axis and gonadotropin production are affected in the polycystic ovary syndrome, resulting in elevation of luteinizing hormone (LH) levels in relation to follicle-stimulating hormone (FSH) levels. As a result of that change, the ovary increases its production of androstenedione from the thecal cells under the affect of increased LH secretion. Androstenedione is metabolized to testosterone by 17-β-hydoxysteroid dehydrogenase. In addition, estrogen production is increased from two sources: the aromatization of testosterone to estradiol and the conversion of androstenedione to estrone in the fatty tissue. The end result of the excess estrogen production in these patients is the suppression of FSH and stimulation of LH levels. Therefore, the ratio of FSH to LH is in favor of excess LH, which leads to the activation of the thecal cells and increased production of androgens.¹¹

The excess androgen production will inhibit the formation of steroid-binding globulins in the liver, and the free testosterone level will be elevated. This might be the case even if the total testosterone level is normal. With the elevation of the free testosterone level, accessibility to the tissues will be high; therefore, peripheral manifestations are developed in the skin in the form of acne eruptions, hirsutism, and oily skin.¹²

The excess estrogen production in these patients, without progesterone effect, will lead to stimulation of the endometrium to undergo proliferation. This process may proceed to hyperplasia; carcinoma of the endometrium could also develop in some of these patients.¹³

Hyperinsulinemia in patients with polycystic ovary syndrome will lead to increased androgen production from thecal cells in the ovaries. Furthermore, hyperinsulinemia inhibits the synthesis of steroid-binding globulins from the liver and adds to the finding of increased free androgens. This will lead to the androgenic properties in polycystic ovary syndrome.¹⁴

In some patients with polycystic ovary syndrome, it has been noticed that they also have some degree of hyperprolactinemia. This is due to the excess estrogen stimulation of the lactotropes.^15,16 Also, in about 30%–50% of patients with polycystic ovary syndrome, there is a slight elevation of dehydroepiandrosterone sulfate from the adrenal glands. This may be due to the excess estrogen level, which causes some blockage in the process of hydroxylation in the adrenal gland.¹⁷

The easy accessibility of testosterone to the skin associated with the increased activity of 5α-reductase leads to the high production of dihydrotestosterone, which leads to all the skin manifestations of patients with polycystic ovary syndrome.¹⁸

Treatment of Infertility and Increased Weight

About 50% of patients with polycystic ovary syndrome are either overweight or obese. This leads to an increase in insulin levels due to an increase in insulin resistance. The end result will be the development of prediabetes or the full picture of diabetes. To help these patients achieve their goal, which includes management of the irregular cycles, skin manifestations, and infertility, they have to be counseled properly for weight loss. This is usually not an easy line of treatment; however, it should be discussed thoroughly with the patient and include referral to a weight loss program. Patients who lost weight have regained normal ovulatory cycles. If the cycles remain irregular, then the management will be more successful compared to management of overweight and obese patients.¹⁹ The use of fertility medications in such patients will not be successful in induction of ovulation even with the use of high medication doses.

This failure is due to an increase in leptin in the serum and follicular fluid. Leptin acts through receptors in granulosa and thecal cells with inhibition of steroidogenesis. Furthermore, in obese patients, there is a decrease in serum adiponectin, which leads to an increase in insulin levels that will stimulate more androgen secretion by the ovary. The end result of thecal cell change is failure of ovulation.²⁰