Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses.

CONTEXT: Metformin treatment of women with polycystic ovary syndrome (PCOS) is widespread, as determined by studies with diverse patient populations. No comparative examination of weight changes or metabolite responses to different doses has been reported. OBJECTIVE: The aim of this study was to determine whether different doses of metformin (1500 or 2550 mg/d) would have different effects on body weight, circulating hormones, markers of inflammation, and lipid profiles. DESIGN: The study included prospective cohorts randomized to two doses of metformin. SETTING: The study was performed at a university teaching hospital with patients from gynecology/endocrinology clinics. PATIENTS: The patients studied were obese (body mass index, 30 to <37 kg/m2; n = 42) and morbidly obese (body mass index, > or =37 kg/m2; n = 41) women with PCOS. INTERVENTION: Patients were randomized to two doses of metformin, and parameters were assessed after 4 and 8 months. MAIN OUTCOME MEASURES: The main outcome measures were changes in body mass, circulating hormones, markers of inflammation, and lipid profiles. RESULTS: Intention to treat analyses showed significant weight loss in both dose groups. Only the obese subgroup showed a dose relationship (1.5 and 3.6 kg in 1500- and 2550-mg groups, respectively; P = 0.04). The morbidly obese group showed similar reductions (3.9 and 3.8 kg) in both groups. Suppression of androstenedione was significant with both metformin doses, but there was no clear dose relationship. Generally, beneficial changes in lipid profiles were not related to dose. CONCLUSION: Weight loss is a feature of protracted metformin therapy in obese women with PCOS, with greater weight reduction potentially achievable with higher doses. Additional studies are required to determine whether other aspects of the disorder may benefit from the higher dose of metformin.

Outcomes of pregnancy complicated by thyroid disease.

AIMS: To perform a case note review of pregnancies complicated by thyroid dysfunction to determine management and therapeutic intervention in relation to pregnancy outcome. METHODS: A retrospective case note analysis of 81 ongoing pregnancies in 70 pregnant women with a history of thyroid dysfunction over a period of 5 years at the Glasgow Royal Maternity Hospital (GRMH), Glasgow, Scotland, United Kingdom. The results of thyroid function tests and whether a change in treatment was instituted were recorded. Thyroid function was assessed by standard laboratory reference ranges for free thyroxine (FT4) and thyroid stimulating hormone (TSH) in all trimesters. Other parameters were also noted. RESULTS: Medication levels needed to be increased in the hypothyroid group (45%), and decreased (38%) in the hyperthyroid group. CONCLUSION: Pregnancy outcome was good in majority of cases given appropriate replacement therapy for stated reference values.

Metformin reduces serum mullerian-inhibiting substance levels in women with polycystic ovary syndrome after protracted treatment.

OBJECTIVE: Assessment of ovarian responses to metformin treatment in obese women with polycystic ovary syndrome (PCOS). DESIGN: Prospective treatment with randomization to two doses of metformin. SETTING: University teaching hospital. PATIENT(S): Obese women (n = 82) with PCOS. INTERVENTION(S): Markers of ovarian function were assessed after 4 and 8 months. MAIN OUTCOME MEASURE(S): Hormone (androgens and mullerian-inhibiting substance [MIS]) changes over time. RESULT(S): There was no difference in the reproductive hormone changes between the doses of metformin, and data were combined for further analyses. Significant responses to treatment were recorded for menstrual frequency and androstenedione (A) (reduction) within the first 4 months of treatment. However, suppression of the elevated circulating MIS concentrations required protracted treatment, because no change was observed in the first 4 months-only in the second 4-month assessment period. CONCLUSION(S): Metformin treatment of PCOS leads to rapid suppression of A and improved menstrual frequency. Suppression of MIS is a delayed response that may be secondary to the development of a cohort of follicles that underwent initial recruitment in an environment of reduced insulin stimulation.

Metformin or antiandrogen in the treatment of hirsutism in polycystic ovary syndrome.

Hirsutism is a common and distressing symptom frequently encountered in women with polycystic ovary syndrome (PCOS), who also show relative insulin resistance. The aim of this trial, in which hirsutism was the primary end point, was to compare the efficacy of the oral antihyperglycemic medication metformin with that of an established treatment, combined ethinyl estradiol and cyproterone acetate. Patients (n = 52) were randomized to receive either metformin (500 mg, three times daily) or Dianette (ethinyl estradiol, 35 micro g; cyproterone acetate, 2 mg) treatment for 12 months, with assessments before treatment, at 6 months, and at 12 months. Both objective and subjective methods of evaluating hirsutism were used, and in addition, patient perceptions were examined. The results show that metformin is potentially an effective treatment for moderate to severe hirsutism in women with PCOS. They also suggest that in some respects (Ferriman-Gallwey score and patient self-assessment), it is more efficacious than the standard treatment (Dianette). The objective evaluation of hair diameter reduction showed that both treatments were moderately effective at multiple anatomical sites. Dianette treatment was responsible for profound suppression of androgen activity, in contrast to metformin, which induced negligible change. However, metformin did reduce markers of insulin resistance. The data suggest that hirsutism may be effectively treated by reducing hyperinsulinemia.

Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome.

Use of metformin in polycystic ovary syndrome (PCOS) is becoming increasingly accepted and widespread, but clinical practice is ahead of the evidence. Although a wide range of benefits in metabolic, reproductive, and clinical measures have been reported from non-randomised trials with metformin, close inspection of results from the adequately controlled studies shows that the benefits are modest. Our aim in this descriptive review is not to define practice guidelines but to improve clinicians' knowledge of the available published clinical evidence, concentrating on the few randomised controlled trials. We also highlight other issues, including hirsutism, acne, pregnancy, and neonatal outcome, that require more attention before clinical recommendations for the use of metformin in PCOS can be formalised. The potentially greater benefits achievable by lifestyle changes alone are also emphasised. We hope that the review will lead to more judicious use of metformin in PCOS and a more structured approach to research.