Tags

Type your tag names separated by a space and hit enter

Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial.

Abstract

Women with oligomenorrhea and polycystic ovaries show a high incidence of ovulation failure perhaps linked to insulin resistance and related metabolic features. A number of reports show that the biguanide metformin improves ovarian function. However, in these trials the quality of evidence supporting ovulation is suboptimal, and few studies have been placebo-controlled. The aim of our study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 94 patients randomized, 2 withdrew before treatment commenced, 47 received placebo, and 45 received metformin (850 mg, twice a day). The numbers discontinuing the study prematurely were higher in the treatment group (n = 15) than the placebo group (n = 5; P < 0.05). The ovulation frequency assessed by the ratio of luteal phase weeks to observation weeks was significantly (P < 0.01) higher in the treated group (23%) compared with the placebo (13%), and the time to first ovulation was significantly (P < 0.05) shorter [23.6 d; 95% confidence interval (CI), 17, 30; compared with 41.8 d; 95% CI, 28, 56]. The proportion of patients failing to ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo group, and the majority of ovulations were characterized by normal progesterone concentrations in both groups. The effect of metformin on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the metformin group. Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the metformin group, whereas the placebo group actually increased weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the metformin-treated group. Metabolic risk factor benefits of metformin treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded after 14-wk metformin or placebo therapy. There was an inverse relationship between body mass and treatment efficacy. We show in a large randomized placebo-controlled trial that metformin treatment improves ovulation frequency in women with abnormal ovarian function and polycystic ovaries significantly but to a modest degree, and protracted treatment improves cardiovascular risk factors. These data support a beneficial effect of metformin in improving ovarian function in women with oligomenorrhea and polycystic ovaries.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    University Department of Obstetrics and Gynecology, Royal Infirmary, Glasgow, G31 2ER, United Kingdom. gqta13@udcf.gla.ac.uk

    , , ,

    Source

    MeSH

    Adult
    Body Mass Index
    Double-Blind Method
    Female
    Fertilization
    Humans
    Hypoglycemic Agents
    Lipoproteins, HDL
    Metformin
    Obesity, Morbid
    Oligomenorrhea
    Ovarian Follicle
    Ovary
    Ovulation
    Patient Dropouts

    Pub Type(s)

    Clinical Trial
    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    11836287

    Citation

    Fleming, Richard, et al. "Ovarian Function and Metabolic Factors in Women With Oligomenorrhea Treated With Metformin in a Randomized Double Blind Placebo-controlled Trial." The Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 2, 2002, pp. 569-74.
    Fleming R, Hopkinson ZE, Wallace AM, et al. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. J Clin Endocrinol Metab. 2002;87(2):569-74.
    Fleming, R., Hopkinson, Z. E., Wallace, A. M., Greer, I. A., & Sattar, N. (2002). Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. The Journal of Clinical Endocrinology and Metabolism, 87(2), pp. 569-74.
    Fleming R, et al. Ovarian Function and Metabolic Factors in Women With Oligomenorrhea Treated With Metformin in a Randomized Double Blind Placebo-controlled Trial. J Clin Endocrinol Metab. 2002;87(2):569-74. PubMed PMID: 11836287.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial. AU - Fleming,Richard, AU - Hopkinson,Zoe E, AU - Wallace,A Michael, AU - Greer,Ian A, AU - Sattar,Naveed, PY - 2002/2/12/pubmed PY - 2002/3/2/medline PY - 2002/2/12/entrez SP - 569 EP - 74 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 87 IS - 2 N2 - Women with oligomenorrhea and polycystic ovaries show a high incidence of ovulation failure perhaps linked to insulin resistance and related metabolic features. A number of reports show that the biguanide metformin improves ovarian function. However, in these trials the quality of evidence supporting ovulation is suboptimal, and few studies have been placebo-controlled. The aim of our study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 94 patients randomized, 2 withdrew before treatment commenced, 47 received placebo, and 45 received metformin (850 mg, twice a day). The numbers discontinuing the study prematurely were higher in the treatment group (n = 15) than the placebo group (n = 5; P < 0.05). The ovulation frequency assessed by the ratio of luteal phase weeks to observation weeks was significantly (P < 0.01) higher in the treated group (23%) compared with the placebo (13%), and the time to first ovulation was significantly (P < 0.05) shorter [23.6 d; 95% confidence interval (CI), 17, 30; compared with 41.8 d; 95% CI, 28, 56]. The proportion of patients failing to ovulate during the placebo-treatment period was higher (P < 0.05) in the placebo group, and the majority of ovulations were characterized by normal progesterone concentrations in both groups. The effect of metformin on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the metformin group. Significant (P < 0.01) weight loss (and leptin reduction) was recorded in the metformin group, whereas the placebo group actually increased weight (P < 0.05). A significant increase in circulating high-density lipoprotein was observed only in the metformin-treated group. Metabolic risk factor benefits of metformin treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded after 14-wk metformin or placebo therapy. There was an inverse relationship between body mass and treatment efficacy. We show in a large randomized placebo-controlled trial that metformin treatment improves ovulation frequency in women with abnormal ovarian function and polycystic ovaries significantly but to a modest degree, and protracted treatment improves cardiovascular risk factors. These data support a beneficial effect of metformin in improving ovarian function in women with oligomenorrhea and polycystic ovaries. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/11836287/Ovarian_function_and_metabolic_factors_in_women_with_oligomenorrhea_treated_with_metformin_in_a_randomized_double_blind_placebo_controlled_trial_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.87.2.8261 DB - PRIME DP - Unbound Medicine ER -