Treating Polycystic Ovary Syndrome May Prevent Infertility
EXECUTIVE SUMMARY
As many as 5 million women nationwide may have polycystic ovary syndrome (PCOS), which is one of the leading causes of infertility. Results of a small study suggest that reducing the amount of abdominal visceral fat and liver fat to normal restores ovulation, reduces the symptoms of androgen excess, and may help prevent subfertility.
- Few agents have been approved specifically for use in polycystic ovary syndrome, and several agents are contraindicated in pregnancy. Insulin-sensitizing agents are indicated for most women with PCOS because they produce positive effects on insulin resistance, menstrual irregularities, anovulation, hirsutism, and obesity.
- About 98% of teens diagnosed with the disorder are prescribed an oral contraceptive for such symptoms as hirsutism and oligomenorrhea.
Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among women in their reproductive years. As many as 5 million women nationwide may suffer from PCOS, which is one of the leading causes of infertility.1
The FDA has approved few agents specifically for use in polycystic ovary syndrome; several other agents are contraindicated in pregnancy.2 Insulin-sensitizing agents are indicated for most women with PCOS because they produce positive effects on anovulation, hirsutism, obesity, menstrual irregularities, and insulin resistance. Rosiglitazone and pioglitazone also are effective for ameliorating hirsutism and insulin resistance. Alone or in combination, metformin and clomiphene are first-line agents for ovulation induction. Insulin-sensitizing agents, oral contraceptives, spironolactone, and topical eflornithine can be used in patients with hirsutism.2 About 98% of teens diagnosed with the disorder are prescribed an oral contraceptive (OC) for such symptoms as hirsutism and oligomenorrhea.3
Now, new research suggests reducing the amount of abdominal visceral fat and liver fat to normal restores ovulation, reduces the symptoms of androgen excess, and may help prevent subfertility.4
In a small study conducted at the University of Barcelona, Lourdes Ibáñez, MD, PhD, professor of pediatrics at the Institut de Recerca Pediàtrica Hospital Sant Joan de Déu and her colleagues enrolled 36 young women with PCOS who were, on average, 16 years of age, and were not pregnant, obese, or sexually active. Study participants experienced their first menstruation at least two years before enrollment, and their excessive body hair and irregular menses could not be attributed to specific causes. Overall, 34 girls completed the study.
Study participants were randomized to receive one of two daily drug combinations: a combined oral contraceptive pill containing 20 mcg ethinyl estradiol plus 100 mg levonorgestrel or a novel drug, SPIOMET (spironolactone 50 mg, pioglitazone 7.5 mg, and metformin 850 mg). Researchers counseled study participants to exercise regularly and eat a Mediterranean diet. The teens took the study drugs for 12 months and were followed without intervention for another 12 months. The safety of SPIOMET in pregnant women was not addressed in this study.
Researchers counted the number of ovulations over two periods: between three and six months after treatment, and between nine and 12 months after treatment, by referring to menstrual diaries and weekly measurements of salivary progesterone. Assessments also were made of body composition; the amount of abdominal, visceral, and hepatic fat; circulating androgens; cholesterol and insulin; carotid artery thickness; and other markers of cardiovascular health.
Prior to treatment, young women with PCOS exhibited more visceral and hepatic fat than age-matched controls, as well as higher androgens and insulin and altered markers of cardiovascular health. Findings indicate that during treatment, those taking SPIOMET normalized more hepatic and visceral fat, insulin, and markers of cardiovascular health; and after treatment, these values remained more normal in the girls who took SPIOMET than in those on oral contraceptives. In comparison to oral contraceptives, SPIOMET was followed by a 2.5-fold higher ovulation rate and a six-fold higher prevalence of normal ovulation; the risk of experiencing abnormally few ovulations was 65% lower, according to the findings. The teens who lost the most hepatic fat were those who ovulated more after treatment, researchers noted.4
“If SPIOMET — the low-dose combination of an anti-androgen plus two insulin-sensitizers — can restore ovulation rates after reducing ectopic fat, later subfertility can potentially be prevented in many women who nowadays depend on expensive and time-consuming fertility techniques to conceive,” Ibáñez said in a statement accompanying the presentation.
Anita Nelson, MD, professor and chair of the obstetrics and gynecology department at Western University of Health Sciences in Pomona, CA, says that the work is “interesting,” but has questions regarding the chosen drug therapies.
“The choice of comparator pill was biased; women with PCOS are generally prescribed pills with low androgenicity or antiandrogenic activity [and] these women received pills with levonorgestrel,” Nelson says. “The tri-therapy with metformin, pioglitazone, and spironolactone leaves the women at risk for irregular bleeding, feminization of a male fetus, and substantial side effects as well as risks, such as hepatic failure.”
Check Diagnosis, Treatment
Guidance issued in 2013 by the Washington, DC-based Endocrine Society directed clinicians to use the Rotterdam criteria for diagnosing PCOS, which calls for the presence of two of the following criteria: polycystic ovaries, androgen excess, or ovulatory dysfunction.5
Establishing a diagnosis of PCOS can be problematic in adolescents and menopausal women, according to the guidance. Hyperandrogenism is central to the presentation in adolescents, while there is no consistent phenotype in postmenopausal women, it notes. Providers should exclude alternate androgen-excess disorders and risk factors for endometrial cancer, mood disorders, obstructive sleep apnea, diabetes, and cardiovascular disease in their evaluation of women with PCOS.5
In a 2015 statement, the Endocrine Society called for further research on establishing diagnostic criteria for adolescents to track how PCOS develops throughout childhood and into reproductive years.6 The authors of the statement argued that earlier diagnoses could lead to other longitudinal studies that could better evaluate targeted PCOS interventions and the metabolic, psychological, and reproductive conditions connected to it.
“If healthcare providers were armed with better strategies for diagnosing PCOS in teenage girls, they would be able to intervene sooner to address risk factors for diabetes and cardiovascular disease,” Richard Legro, MD, vice-chair of research in the department of obstetrics and gynecology and professor of obstetrics and gynecology and public health sciences at Penn State College of Medicine and chair of the statement task force said at the time. “Earlier diagnosis is crucial for gaining a better understanding of the long-term effects of PCOS.”
REFERENCES
- Franks S. Polycystic ovary syndrome. N Engl J Med 1995;333:853-861.
- Radosh L. Drug treatments for polycystic ovary syndrome. Am Fam Physician 2009;79:671-676.
- Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev 2000;21:363.
- Ibáñez L, del Rio L, Diaz M, et al. Ovulation rates after randomized interventions for polycystic ovary syndrome in adolescent girls. Presented at ENDO 2017. Orlando; April 2017.
- Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2013; 98:4565-4592.
- Dumesic DA, Oberfield SE, Stener-Victorin E, et al. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev 2015;36:487-525.
Results of a small study suggest that reducing the amount of abdominal visceral fat and liver fat to normal restores ovulation, reduces the symptoms of androgen excess, and may help prevent subfertility.
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