Polycystic ovary syndrome (PCOS) is one of the most commonly encountered endocrinopathies in women of fertile age Citation[1,2] and remains one of the most enigmatic reproductive endocrinologic disorders. The diagnostic criteria of PCOS have still not been unified; three sets of criteria are presently used Citation[3–5]. This discrepancy complicates the comparison of PCOS-related studies. The exact pathogenesis of PCOS has still not been clarified. Exaggerated ovarian steroid production Citation[6,7], increased secretion of luteinizing hormone Citation[8] and insulin resistance Citation[9] represent the PCOS features. However, the exact role of each of these factors in the pathogenesis of this syndrome is not known. There is strong evidence that PCOS could have a genetic component. Between 20 and 40% of female first-degree relatives are affected by the disorder, exaggerating the PCOS prevalence in the common population Citation[10,11]. PCOS appears to be inherited as a complex disorder in which several genetic variants are present, all contributing together with lifestyle and environmental effects to the manifestation of the disorder Citation[12].
The natural history of PCOS is poorly defined. There is some indication from animal experiments that all of the aforementioned abnormalities could be induced by prenatal androgen excess Citation[13]. The endocrinological features of PCOS are believed to ameliorate with the age approaching menopause; however, there are studies supporting the view that women with PCOS still have androgen excess and some metabolic derangements connected with insulin resistance in their menopausal years Citation[14,15].
Since we do not know the unique cause or causes of PCOS, we do not have a causal therapy. The most often used treatments are combined oral contraceptives (COCs). COCs lead to the suppression of gonadotropin secretion and of ovarian activity and they increase production of sex hormonebinding globulin leading to a decrease in free androgen levels Citation[16]. These effects lead to regular bleeding and a decrease in the severity of cutaneous manifestations of hyperandrogenemia, such as acne or hirsutism. They can, however, have an unfavourable effect on insulin sensitivity Citation[16]. There are still no studies concerning longterm changes in insulin sensitivity and its reversibility in PCOS after COCs. When healthy former COC users were examined, they did not have an increased incidence of diabetes, which indirectly supports the view that changes in insulin sensitivity are reversible after discontinuation of COCs. There is no proof that COCs could ameliorate the incidence of metabolic consequences in PCOS. Cutaneous manifestations of PCOS are aggravated after COC discontinuation.
Metformin has been used in the management of PCOS since 1994 Citation[17]. It has multiple beneficial effects extending beyond improvement in hepatic gluconeogenesis and intestinal effects to the decrease in ovarian androgen production and amelioration of luteinizing hormone secretion Citation[18]. When metformin was discontinued, the positive effect on insulin sensitivity disappeared Citation[19]. As far as we know, there are no longterm studies concerning ovarian steroidogenesis and metformin discontinuation. In the aforementioned study, serum testosterone and sex hormone-binding globulin improved after metformin treatment, but was not different from the baseline 6 and 12 months after treatment discontinuation Citation[19]. These data suggest that beneficial effects of metformin treatment are seen only when treatment is administered without any long-term effects.
Obesity is often connected with PCOS Citation[20]. There are data indicating that weight reduction leads to an improvement in menstrual cycle frequency and in androgen levels Citation[21]. It is tempting to think that in some cases obesity could be a major factor contributing to the development of PCOS according to data from the bariatric surgery study. Morbidly obese women with PCOS have a full disappearance of all PCOS symptoms when large body weight loss was achieved after surgery Citation[22].
Antiandrogens are used in the treatment of cutaneous manifestations of PCOS and are effective in the reduction of acne and hirsutism Citation[23,24]. Flutamide was shown in one study to improve pituitary sensitivity to progesterone in women with PCOS Citation[25]. If it is replicated by others, it will be the first medical treatment of PCOS capable to of changinge the life course of PCOS.
In conclusion, we still have only episodic facts suggesting that there are treatment modalities that could completely resolve PCOS. Since pathogenesis is not fully understood in PCOS, in which a strong genetic component is seen at least in some cases, we should not expect to have a single long-term effective treatment leading to a cure for this common disorder.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
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