Metformin and PCOS: Improving Menstrual Cycle and Hormone Profiles

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The group with the greatest improvement compared to baseline was normal weight with elevated testosterone.
The group with the greatest improvement compared to baseline was normal weight with elevated testosterone.

Women diagnosed with polycystic ovary syndrome (PCOS) placed on metformin for 24 months may experience improvements in menstrual cycle and hormone profiles, according to an article published in the Journal of Clinical Endocrinology & Metabolism.

Researchers identified 119 normal weight and overweight women diagnosed with PCOS in Taiwan who had attended an endocrinology clinic due to menstrual irregularities or symptoms of hyperandrogenism, with polycystic ovaries subsequently found on ultrasound imaging.

The primary outcome of the study was the number of women with PCOS who reported normal menses after treatment with metformin.

During the study, the women were stratified according to either body mass index (BMI) or testosterone status, creating 4 subgroups: normal weight-normal testosterone, normal weight-elevated testosterone, overweight-normal testosterone, and overweight-elevated testosterone.

Regardless of whether the women were stratified by testosterone or BMI, the percentage of women found to have normal menstrual cycles after being treated with metformin were generally higher when compared with baseline values.  Women in the normal weight subgroup were noted to show significant improvement after 3 months when stratified based upon BMI.

Both subgroups stratified by testosterone were found to have significant improvements after the first 6 months of treatment, with patients in the normal testosterone groups maintaining a constant slope from treatment months 3 to 24 (slope estimate = 0.033; standard error [SE], 0.014, P <.05), with patients in the elevated testosterone groups diverging from a similar slope after 6 months (slope estimate = 0.088; SE, 0.073). The normal weight-elevated testosterone group showed the greatest improvement compared with baseline, with an odds ratio of 7.21 (95% CI, 2.35-22.17). 

All four subgroups were found to have improvements after 6 months of therapy, with an increase from 42% to 47% in women with normal menses.  No further changes in menstrual patterns were noted except in women in the overweight-normal testosterone subgroup, who continued to demonstrate improvements up to 12 months after therapy initiation, and the highest predicted percentage of patients with a normal menstrual cycle after a full 24 months of therapy (OR 0.63; 95% CI, 0.47-0.77).

Study results found that BMI, testosterone, free androgen index, luteinizing hormone levels, and luteinizing hormone/follicle-stimulating hormone ratios to be significantly lower after 24 months of treatment when compared with baseline values in both subgroups.  There was a significant decrease in values after 6 months of treatment, with no further significant changes from 6 months to 24 months.  Serum sex hormone-binding globulin (SHBG) was found to be significantly lower than baseline values at 12 months, yet higher than baseline at 24 months only in the normal-weight subgroup, while changes in SHBG were not significant in the overweight subgroup between months 12 and 24.

Researchers concluded that metformin is indeed associated with improvements in menstrual cycle regularity and hormonal patterns in normal weight and overweight women with PCOS placed on metformin drug therapy for 24 months as all four BMI/testosterone subgroups demonstrated similar rates of achieving normal menses after 6 months of taking metformin, with the greatest improvement from baseline in the normal weight-elevated testosterone subgroup, and the longest duration of improvement in the overweight-normal testosterone subgroup.  There are differences in women's responses to treatment with metformin as influenced by BMI and testosterone phenotypes.  Clinicians should be aware of the effectiveness of metformin and consider its use in women with PCOS.

Reference

Yang PK, Hsu CY, Chen MJ, et al. The efficacy of 24-month metformin for improving menses, hormone and metabolic profiles in polycystic ovary syndrome [published online January 9, 2018]. J Clin Endocrinol Metab. doi:10.1210/jc.2017-01739

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