Dataset Information

Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: A randomized, double-blind, placebo-controlled study.

ABSTRACT: 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.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).Cross-over, randomized, double-blind, placebo-controlled study.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.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 ?U/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.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.EudraCT 2011-000439-10.

SUBMITTER: Pelusi C

PROVIDER: S-EPMC5590732 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: A randomized, double-blind, placebo-controlled study.

Pelusi Carla C Giagulli Vito Angelo VA Baccini Margherita M Fanelli Flaminia F Mezzullo Marco M Fazzini Alessia A Bianchi Nicola N Carbone Matteo Domenico MD De Pergola Giovanni G Mastroroberto Marianna M Morselli Labate Antonio Maria AM Pasquali Renato R

PloS one 20170908 9

<h4>Context</h4>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.<h4>Objective</h4>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).<h4>Design</h4>Cross-over, randomized, double-blind, placebo-controll ...[more]

PMID: 28886024

Similar Datasets

Project description:BackgroundClomiphene citrate (CC) is a selective estrogen receptor modulator (SERM) used to stimulate ovulation in women. CC is used off-label in men to increase levels of endogenous testosterone (T) while potentially improving semen parameters by downregulating the inhibitory feedback of estradiol (E) on the male hypothalamus. Our objective was to determine whether pre-treatment E level is associated with greater total testosterone (TT) response to treatment with CC in men with low T.MethodsFollowing IRB approval (The University of Miami IRB No. 20170849), retrospective chart review was performed for all men prescribed CC (25 mg every other day) between January 1, 2015 and December 31, 2018. Age, body mass index (BMI), and prescription date were recorded for all patients. Pre- and post-treatment E, total T (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels were recorded for all patients as well. Only men with pretreatment TT <300 ng/dL were included in the analysis in order to focus our study on men with low TT. Univariate linear regression analysis was performed to determinate the percent change in TT following CC treatment (dependent variable) and pre-treatment E and other variables including age, BMI, FSH, and LH (independent variables).ResultsA total of 69 men with TT <300 ng/dL received CC 25 mg every other day. Mean age and BMI were 33.3±7.31 years and 35.4±5 kg/m2 respectively. Median pre-treatment E, TT, FSH, and LH were 18 [11.35-24.6] pg/mL, 226 [156-262] ng/dL, 5.1 [2.98-8.05] mIU/mL, and 4.5 [2.6-6.8] mIU/mL respectively. Post-treatment TT was 389 [263-592] ng/dL and TT% change was 102 [45.51-176.75]. Univariate linear regression showed that pre-treatment E (B=-0.595; R2=0.001; P=0.757) did not significantly predict TT% change. TT% change could be significantly predicted by age in years (B=-7.428; R2=0.057; P=0.048), pre-treatment FSH (B=-8.362; R2=0.068; P=0.041), and pre-treatment LH (B=-20.67; R2=0.096; P=0.027).ConclusionsPre-treatment E level does not appear to predict treatment response with CC in men with low T.

Project description:Introduction: Which is optimal to treat clomiphene citrate-resistant polycystic ovary syndrome (CCR-PCOS) with LOD or metformin remains a problem. There are three inconsistent or even contradictory views. Objectives: The present meta-analysis aimed to evaluate the effectiveness and safety of Metformin with or without CC and to compare them with LOD with or without CC (Met/Met-CC vs. LOD/LOD-CC) in women with CCR-PCOS who also have anovulation. Data source: The PubMed, Cochrane, and Embase databases were searched to identify relevant studies reported between 1 Jan 1966 and 31 Aug 2019; the search was updated on 17 May 2022. Study eligibility criteria: We included randomized controlled trials (RCTs) of CCR-PCOS that had considered Met/Met-CC and LOD/LOD-CC as the exposure variables and fertility as the main outcome variable. Study appraisal and synthesis methods: We assessed study quality using the Cochrane risk-of-bias tool. The primary effectiveness outcome was live birth/ongoing pregnancy rate and the primary safety outcome was miscarriage rate. A fixed-effect meta-analysis was performed. The robustness of the results was assessed using sensitivity analyses. Meta-regression and subgroup analysis were performed to examine the reasons for heterogeneity. Publication bias was examined using the funnel plot, Egger linear regression, and Begg rank correlation tests. The quality of this meta-analysis was estimated according to the GRADE approach. This meta-analysis has been registered in PROSPERO (CRD42021240156). Results: Among 71 potentially relevant studies, we included five RCTs in our meta-analysis. We found no difference in effectiveness between Met-CC and LOD in terms of live birth/ongoing pregnancy (RR = 1.02, 95% CI: 0.87-1.21, z = 0.28; p = 0.780), and miscarriage rates (RR = 0.79, 95% CI: 0.46-1.36, z = 0.86; p = 0.390). I2 tests results revealed moderate or no heterogeneity (I2 = 51.4%, p = 0.083; I2= 0.0%; p = 0.952). Sensitivity analysis confirmed the robustness of the results. Funnel plot, Egger linear regression, and Begg rank correlation tests implied no publication bias (p > 0.05). LOD was more expensive than Met (€1050 vs. €50.16). The evidence quality was moderate. Conclusion: There is no evidence on the difference in the outcomes between the two interventions regarding ovulation, pregnancy, and live birth. As LOD is an invasive procedure and carries inherent risks, the use of Met/Met-CC should be the second-line treatment for women with CCR-PCOS. Systematic Review Registration: identifier CRD42021240156.

Project description:BackgroundThe aim of this study was to compare the efficacy of the combination of clomiphene citrate (CC) and letrozole to that of CC alone in inducing ovulation in infertile women with ovulatory dysfunction.MethodsA randomized controlled trial was conducted at a single academic medical center between November 2020 and December 2021. Anovulatory infertility females, aged 18 to 40, were evenly distributed by a computer-generated block of four into two treatment groups. A "combination group" received a daily dose of CC (50 mg) and letrozole (2.5 mg), while a "CC-alone group" received a daily dose of CC alone (50 mg). The study medications were administered on days 3 through 7 of menstrual cycle. The primary outcome was the ovulation rate, defined by serum progesterone levels exceeding 3 ng/mL at the mid-luteal phase. The secondary outcomes were ovulation induction cycle characteristics, endometrial thickness, conception rate, and adverse events.ResultsOne hundred women (50 per group) were enrolled in the study. The mean age was not significantly different in both groups: 31.8 years in the combination group and 32.4 years in the CC-alone groups (P = 0.54). The prevalence of polycystic ovary syndrome in the combination and CC-alone groups was 48% and 44%, respectively (P = 0.841). According to intention-to-treat analysis, the ovulation rates were 78% and 70% in the combination and CC-alone groups, respectively (P > 0.05). There was no significant difference in the mean endometrial thickness or the number of dominant follicles of the groups. No serious adverse events were observed in either group.ConclusionsOur study found no significant difference between the combination of CC and letrozole and CC alone in inducing ovulation in infertile women with ovulatory dysfunction in one cycle. The small number of live births precluded any meaningful statistical analysis. Further studies are needed to validate and extend our findings beyond the scope of the current study.Trial registrationThe study was registered at https://www.thaiclinicaltrials.org with the following number: TCTR20201108004 and was approved on 08/11/2020.

Dataset Information

Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: A randomized, double-blind, placebo-controlled study.

Publications

Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: A randomized, double-blind, placebo-controlled study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets