Efficacy of Treatments for Polycystic Ovarian Syndrome Management in Adolescents

Reem A Al Khalifah; Ivan D. Florez; Michael J. Zoratti; Brittany Dennis; Lehana Thabane; Ereny Bassilious


J Endo Soc. 2021;5(1) 

In This Article

Abstract and Introduction


Limited evidence on treatment options for polycystic ovarian syndrome (PCOS) has led to considerable variation in health care practices. We aimed to compare the effects of metformin and/or oral contraceptive pills (OCP) in combination with pioglitazone, spironolactone, flutamide, and lifestyle interventions among adolescents aged 11 to 19 years with PCOS. Literature searches were performed in Medline, Embase, and the Cochrane Central Register of Controlled Trials from database inception through December 2018, with no language restriction. Two reviewers screened titles and abstracts, assessed full text eligibility, and extracted information from eligible trials. Evidence was synthesized through network meta-analyses (NMA) using a Bayesian random-effects approach. We identified 37 randomized controlled trials, in which 2400 patients were randomized. NMA showed no statistically important difference among all interventions to improve menstrual regulation or body mass index. Moderate-quality evidence showed hirsutism scores were reduced by multiple interventions that included single and combination medications namely; lifestyle intervention, metformin, OCP, spironolactone, pioglitazone, metformin-OCP, metformin-spironolactone, and metformin-flutamide against placebo. Moderate-quality evidence showed OCP results in more dysglycemia compared to metformin (odds ratio, 2.98; 95% credible interval, 1.02–8.96), no intervention resulted in dysglycemia reduction. In conclusion, metformin and OCP as monotherapy or in combination with other interventions compared with placebo can reduce hirsutism scores, but none of these medications lead to effective menstrual cycle regulation or weight reduction. However, the use of OCP leads to worse cardiometabolic risk factors. Further research into new treatment options is urgently needed.


Polycystic ovarian syndrome (PCOS) is a common endocrine reproductive disease affecting 1.8% to 15% of women.[1–3] The estimates are variable according to the diagnostic criteria used and the ethnic background of the women. PCOS is diagnosed based on a presentation with 2 of the following: clinical or biochemical hyperandrogenism, ovulatory dysfunction, or polycystic ovaries on ultrasound.[4,5] However, diagnosing PCOS among adolescents remains difficult specially in the first 2 years after menarche. PCOS increases risk of dysglycemia, hyperlipidemia, and obesity.[6–18] PCOS is associated with increased risk for the development of endometrial hyperplasia and consequent development of endometrial cancer, infertility, pregnancy loss, and premature delivery. Moreover, patients with PCOS report low perceived health quality, often citing issues with weight control, hirsutism, acne, menstrual irregularity, and infertility as the primary drivers.[19–21]

Treatment strategies, although variable and controversial because of lack of evidence, focus primarily on controlling symptomatology rather than treating the underlying etiology with the implementation of lifestyle intervention, and the use of either oral contraceptive pills (OCP), or metformin.[4,5,22,23] However, this approach typically fails to achieve a good response and does not mitigate the risk of developing long-term complication.[24]

Research to date has failed to define the ideal treatment approach. For example, studies in adolescents treated with various standards of care have been underpowered to draw conclusions with respect to important patient outcomes such as menstrual regulation, hirsutism, and dysglycemia.[24] We recently described the evidence for randomized controlled trials (RCTs) of metformin monotherapy compared with OCP for the treatment of adolescents with PCOS.[24] Although very few trials met the review criteria, which were categorized as very low-quality evidence, we did identify a potential reduction in the incidence of dysglycemia with the use of metformin. In addition, we identified a large number of trials that compared other treatment approaches such as placebo, spironolactone, flutamide, lifestyle modification, and pioglitazone to either metformin or OCP.[24] Given that many of the treatment combinations available to treat PCOS have not been compared in head-to-head randomized trials, we conducted a systematic literature review and network meta-analysis to assess the following objectives: (1) the efficacy and safety of treatments, including metformin monotherapy, OCP monotherapy, and various combination therapies, for adolescent women with PCOS; and (2) assess the efficacy of different OCPs formulations used to treat hirsutism.