Advances in Treatment Options for Polycystic Ovary Syndrome

US Endocrinology, 2012;8(1):57-64

Abstract:

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy seen in women of reproductive age. Clinical concerns relating to PCOS range from ovulatory infertility and menstrual disorders to risk of diabetes and cardiovascular disease. Hormonal contraceptives have been the mainstay of the management of common PCOS symptoms, such as menstrual irregularity and clinical stigmata of androgen excess (i.e., hirsutism and acne). An appreciation of the relevance of metabolic pathways in the pathophysiology of PCOS is relatively recent, and has translated into an expansion of the therapeutic strategies available for the management of PCOS. Insulin sensitizers were one of the first metabolic modulators to be incorporated in the clinical management paradigm, albeit with mixed results. Recognizing that insulin resistance is central to the pathophysiology of PCOS, newer agents—e.g., thiazolidinediones— followed, with almost comparable efficacy to metformin. Statins and most recently incretins constitute novel therapies with distinct metabolic targets that seem to hold promise in the management of PCOS. In tandem with the expansion in pharmaceuticals, a host of complementary and alternative medical therapies have generated interest for purported promise in the management of PCOS, including vitamin D, acarbose, and myo-inositol. The therapeutic options for managing PCOS-related infertility have also expanded. Clomiphene citrate (CC) has long been the first-line strategy for ovulation induction in the setting of anovulatory infertility; however, aromatase inhibitors are fast gaining acceptance as an ovulation induction strategy, with results comparable or even better than those seen with CC. An increasing level of therapeutic sophistication is reflected in ovarian stimulation protocols judiciously using gonadotropins, gonadotropin-releasing hormone antagonists, the procedure of ovarian drilling, and assisted reproductive technologies with in vitro oocyte maturation.
Keywords: Polycystic ovary syndrome, androgen, oral contraceptive, antiandrogen, spironolactone, finasteride, flutamide, eflornithine, insulin, metformin, thiazolidinediones, incretins, statins, acarbose, myo-inositol
Disclosure: The authors have no conflicts of interest to declare.
Received: April 24, 2012 Accepted May 08, 2012 Citation US Endocrinology, 2012;8(1):57-64
Correspondence: Lubna Pal, MBBS, MRCOG, MS, Yale Reproductive Endocrinology, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06510, US. E: Lubna.pal@yale.edu

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, with an approximate prevalence of 6–10 %.1–3 Characterized by clinical features of hyperandrogenism (such as hirsutism) and/or biochemical androgen excess and ovulatory dysfunction, PCOS is additionally associated with a spectrum of comorbidities that include infertility, increased risk of type 2 diabetes and of cardiovascular disease (CVD), psychological burden, and risk of endometrial pathologies including endometrial cancer.2–4 The therapeutic approach to PCOS entails a focus on the overt presenting complaint(s) (e.g., oligomenorrhea, clinical hyperandrogenism, ovulatory infertility) as well as on the metabolic burden that predisposes this patient population to a spectrum of comorbidities in the long run, including type 2 diabetes and CVD. In this article, the authors have attempted to provide an overview of the treatment options that offer therapeutic benefit in PCOS.

Treatment Options for Targeting Common Symptoms Combined Oral Contraceptives
Having long been used as the first-line treatment in PCOS management, combined oral contraceptives (COCs) offer not just menstrual regulation and endometrial protection, but also a benefit against cutaneous stigmata of hyperandrogenism in women with PCOS.5–7 Mechanisms whereby COCs mediate improvements in PCOS-related symptoms include:

  • a suppression of pituitary luteinizing hormone (LH), thereby reducing the stimulant effect of LH on androgen production by the ovarian theca cells;
  • an increase in hepatic sex hormone binding globulin (SHBG) directly resulting from the estrogen component in the COC; the net effect is a decline in the free androgen levels and hence an improvement in the clinical features of hyperandrogenism (e.g., acne and hirsutism); and
  • the antiproliferative effects of the progestin component of the COC formulation, which offers protection against proliferative endometrial pathologies that oligomenorrheic and insulin-resistant women are particularly at risk of.



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Keywords: Polycystic ovary syndrome, androgen, oral contraceptive, antiandrogen, spironolactone, finasteride, flutamide, eflornithine, insulin, metformin, thiazolidinediones, incretins, statins, acarbose, myo-inositol
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