Morin-Papunen, L. C., Koivunen, R. M., Ruokonen, A., & Martikainen, H. K. (1998). Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome. Fertility and Sterility, 69(4), 691-696. https://doi.org/10.1016/s0015-0282(98)00011-9
Morin-Papunen LC, Koivunen RM, Ruokonen A, Martikainen HK. Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome. Fertil Steril. 1998;69(4):691-696. doi:10.1016/s0015-0282(98)00011-9
Morin-Papunen, Laure C., et al. "Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome." Fertility and Sterility, vol. 69, no. 4, 1998, pp. 691-696.
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Department of Obstetrics and Gynecology, Oulu University Hospital, Wellbeing Services County of North Ostrobothnia, 90220 Oulu, Finland
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RRM Academy Synopsis
Metformin improved menstrual patterns in women with PCOS
Metformin improved the menstrual pattern in 68.8% of women who began with menstrual disturbances. The prospective study followed 20 women with polycystic ovary syndrome (PCOS), also named PMOS (Polyendocrine Metabolic Ovarian Syndrome). Body mass index and blood pressure stayed the same during 4 to 6 months of treatment.
About 7 in 10 women with menstrual disturbances had a more regular menstrual pattern on metformin. Source: Morin-Papunen LC et al., 1998, PMID 9548159.Study at a glance, Prospective study of 20 women with polycystic ovary syndrome: Metformin improved menstrual patterns in women with PCOS. Source: Morin-Papunen LC et al., 1998, PMID 9548159.
Key Findings
Eleven women (68.8% of those with menstrual disturbances before therapy) had a change in menstrual pattern at 4 to 6 months of treatment.
Six women with oligomenorrhea (infrequent periods) achieved irregular cycles, three women with irregular cycles achieved regular menses, and two women with amenorrhea (absent periods) developed oligomenorrhea.
Hirsutism score, body mass index, waist-hip ratio and blood pressure showed no significant change, and the changes in ovarian volume were not significant.
Mean testosterone fell significantly at 2 months and returned close to baseline by 4 to 6 months; free testosterone fell significantly by 4 to 6 months but stayed above the reference range.
Fasting insulin decreased significantly at 4 to 6 months (P = 0.04); the insulin area under the curve during glucose tolerance testing in 10 women decreased significantly (P = 0.01).
Interpretation
The study is a prospective, single-group treatment series. Thirty-one women were recruited, and the 20 who continued for 4 to 6 months were analyzed; three of the 11 who stopped reported vomiting and diarrhea. The authors note that they could not assess how many cycles were ovulatory. They conclude that most women tolerated metformin and that it may help obese women with PCOS and menstrual disturbances. In the authors' assessment, women with hirsutism did not seem to benefit.
RRM Context
Restorative reproductive medicine seeks the hormonal and metabolic causes of missed ovulation in PCOS. The authors name insulin resistance as a basic problem of the syndrome. They observe that suppressive medications such as oral contraceptives leave it in place. Cycle regularity is one sign of ovulatory function, and cycle charting tracks it over time.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To determine the clinical, hormonal, and biochemical effects of 4-6 months of metformin therapy in obese patients with polycystic ovary syndrome (PCOS).
Design
Prospective study.
Setting
The Gynecological Endocrine Unit of University Central Hospital, Oulu, Finland.
Patients
Twenty obese patients with PCOS.
Interventions
Patients were treated with 0.5 g of metformin three times daily for 4-6 months.
Main Outcome Measures
Clinical symptoms, menstrual pattern, and hirsutism, as well as serum concentrations of sex steroids, sex hormone-binding globulin (SHBG), gonadotropins, and lipids were assessed during the treatment.
Results
Eleven women (68.8% of the women with menstrual disturbances) experienced more regular cycles during therapy. No changes in hirsutism, body mass index, or blood pressure occurred. The mean testosterone level was decreased significantly after 2 months of treatment but returned to the starting level by 4-6 months. Free testosterone levels decreased significantly during the treatment. There was no significant change in the levels of other sex steroids or lipids measured at 4-6 months of treatment.
Conclusions
Metformin therapy is well tolerated by the majority of patients and may be clinically useful, especially in obese patients with PCOS and menstrual disturbances.
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