Abstract
BackgroundMetformin plays a consolidated role in the management of polycystic ovary syndrome (PCOS). However, there is no clear answer on how long we should treat and on how long its beneficial impact sustain after we stop treatment. We compared the effects of metformin withdrawal after long-term (LT) and short term (ST) treatment in PCOS women that had previously well responded to metformin.MethodsWe conducted observational longitudinal study including 44 PCOS women (31 (28–36) years and BMI 32.5 (27.7–34.9) kg/m2) that were followed for 6 months after metformin withdrawal. Prior inclusion, ST group had been treated with metformin on average for 1.03 ± 0.13 year, LT group for 5.07 ± 2.52 years. We followed anthropometric, metabolic, reproductive parameters and eating behavior as assessed by TFEQ-R18.ResultsAfter metformin withdrawal, ST group gained significant amount of weight (from 92 (75.5–107.3) kg to 96 (76–116) kg; p = 0.019). Weight tended to increase also in LT users (from 87 (75–103) to 87 (73–105) kg; p = 0.058). More women in LT group maintained stable weight (27% in LT group vs 15% in ST group). Eating behavior deteriorated in both groups. Withdrawal of metformin resulted in a decrease of menstrual frequency (6 (6–6) to 6 (4–6) menstrual bleeds per 6 months; p = 0.027) and in borderline increase of androstenedione (6.4 (4.6–7.6) to 7.8 (4.8–9.6) nmol/L; p = 0.053) in LT group. Waist circumference, HOMA and glucose homeostasis remained stable in both groups. There were no differences between groups at 6-month follow up.ConclusionCollectively, present study implies some metabolic and endocrine treatment legacy in both groups as well as some group-specific deteriorations in clinical parameters 6 months after metformin withdrawal.Trial registration: The study is registered at Clinical Trials with reference No. NCT04566718
Highlights
Metformin plays a consolidated role in the management of polycystic ovary syndrome (PCOS)
Treatment with metformin is well established for patients with PCOS and impaired glucose homeostasis or type 2 diabetes mellitus (T2DM), when lifestyle intervention (LSI) is insufficient and for management of menstrual irregularity if women are unable to take oral contraceptives [1, 2, 8]
Inclusion criteria were PCOS defined by the Rotterdam criteria, phenotype A, characterized by concomitant presence of clinical or biochemical hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology (PCOM) [14, 15], continuous treatment with metformin monotherapy 1000 mg BID, age > 18 years, body mass index (BMI) ≥ 25 kg/ m2, normal glucose homeostasis on metformin treatment prior the inclusion, and informed consent to discontinue metformin according to the study protocol
Summary
Metformin plays a consolidated role in the management of polycystic ovary syndrome (PCOS). The latest international guidelines further advise a consideration of metformin as adjunct to LSI in adult women with PCOS with body mass index (BMI) ≥ 25 kg/m2, regardless of the presence of glucose disturbances and menstrual irregularity, for management of weight and preventing or slowing progression to adverse cardiometabolic outcomes [1]. The evidence supporting these recommendations and current clinical practice [1, 2] are mainly provided from short term studies and meta-analysis designed from 3 up to 12 months [9, 10]. Less than 25% of patients remained adherent to metformin for more than 5 years with further dropout to only 6% of those still adherent to metformin at the 10th year of follow up [13]
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