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Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic
Carla Pelusi1, Vito Angelo Giagulli2, Margherita Baccini1
1Division of Endocrinology and Center for Applied Biomedical Research, Department of Medical & Surgical Sciences, Alma Mater Studiorum, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
Context:
Low testosterone (T) levels are often found in obese men with impaired glucose tolerance (IGT) and overt type 2 diabetes (T2DM); however, the mechanisms underlying this condition and its correct therapy are still under debate.
Objective:
To evaluate the effectiveness of clomiphene citrate (CC) in increasing endogenous T levels in obese men with low serum T and with IGT or T2DM treated with metformin (MET).
Design:
Cross-over, randomized, double-blind, placebo-controlled study.
Methods:
24 obese men, aged 47.3 ±. 6.3 (range 35-55 years), with low T level (≤3 ng/mL) and naïve diagnosis of IGT or T2DM were included. Subjects were randomized to CC 25 mg/day or placebo (Plac) with MET 2 g/day for 3 months. After a 6-week wash-out period, subjects were moved to the alternative arm for additional 3 months. Clinical evaluation and blood exams performed prior to and at the end of treatment.
Results:
Of 24 randomized, 21 were evaluable, classified as IGT (n = 11) or T2DM (n = 10). Compared to baseline levels, T levels increased significantly after 3 months of CC treatment (3.03±0.80 to 5.99±1.67 ng/mL P<0.001) but not after the Plac treatment (2.87±0.78 to 3.09±0.84 ng/mL P<0.001 between the treatments). T changes were similar in IGT and T2DM subjects. Gonadotropins as well raised significantly after CC treatment (LH 3.83±1.45 to 8.53±6.40 mU/mL; FSH 4.84±1.67 to 10.15±5.08 mU/mL P<0.001 respectively), whereas no changes for LH (3.51±1.59 to 3.63±1.39 mU/mL) but a smooth increased for FSH (4.61±2.49 to 5.39±2.65 mU/mL; P = 0.004) were shown after Plac treatment (LH P = 0.001 and FSH P = 0.002 between treatments). Furthermore, fasting glucose (106.8±23.2 to 101.1±25.7 mg/dL; P = 0.004), insulin (19.3±12.1 to 15.6±10.1 μU/mL; P = 0.010) and HOMA-IR (4.94±2.89 to 3.69±2.12; P = 0.001) decreased significantly during the CC treatment period, whereas no significant changes were observed in any of these parameters in the Plac treatment.
Conclusions:
A low dose of CC therapy was able to significantly increase serum T levels in all participants with mild modifications of clinical and metabolic parameters.
Trial Registration:
EudraCT 2011-000439-10.
Insights
Clomiphene citrate effectively boosted testosterone levels in obese men with impaired glucose tolerance or type 2 diabetes. This treatment also improved metabolic markers, suggesting a therapeutic role for testosterone replacement.
Area of Science:
- Endocrinology
- Metabolic Syndrome
- Male Reproductive Health
Background:
- Obesity is linked to low testosterone (T) and glucose metabolism issues.
- Mechanisms and optimal therapy for low T in obese men with glucose intolerance remain debated.
Purpose of the Study:
- To assess clomiphene citrate's (CC) efficacy in raising endogenous T in obese men with low T and either impaired glucose tolerance (IGT) or type 2 diabetes (T2DM).
- To evaluate CC's impact on metabolic parameters when co-administered with metformin (MET).
Main Methods:
- A randomized, double-blind, placebo-controlled, cross-over study.
- 21 obese men (IGT or T2DM, low T) received CC (25 mg/day) or placebo with metformin (2 g/day) for 3 months, followed by a 6-week washout and then switched treatments.
Main Results:
- CC significantly increased serum T levels (3.03 to 5.99 ng/mL, P<0.001) compared to placebo (2.87 to 3.09 ng/mL, P<0.001).
- CC also elevated gonadotropins (LH, FSH) and significantly reduced fasting glucose, insulin, and HOMA-IR.
- Metabolic improvements were observed without significant changes in the placebo group.
Conclusions:
- Low-dose clomiphene citrate therapy effectively increases testosterone levels in obese men with IGT or T2DM.
- CC treatment led to mild but significant improvements in clinical and metabolic parameters.
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