Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study

Soares, Andressa Heimbecher; Horie, Nídia Celeste; Chiang, Lucas Augusto Piccinin; Caramelli, Bruno; Matheus, M G; Campos, Alexandre; Marti, Luciana Cavalheiro; Rocha, Fabiana; Mancini, Márcio C.; Costa, Elaine Maria Frade; Cercato, Cíntia

doi:10.1038/s41366-018-0105-2

Cited by 40 publications

(87 citation statements)

References 43 publications

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“…A small decrease in BMI and waist circumference was seen in men with IGT 20. Furthermore, an increase was reported for lean body mass, fat‐free mass, and skeletal muscle mass 17…”

Section: Resultsmentioning

confidence: 99%

Aromatase inhibitors and selective estrogen receptor modulators: Unconventional therapies for functional hypogonadism?

2019

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Introduction Functional hypogonadism increases in prevalence due to aging as well as an overall increase of obesity. Aromatase inhibitors (AIs) and selective estrogen receptor modulators (SERMs) could be an alternative for testosterone replacement therapy (TRT), but have not yet been established as common clinical practice. Methods We conducted a thorough search of the literature published between 2009 and 2018. Only RCTs published in English were included. We assessed the impact of AIs and SERMs on gonadal steroids, sexual function and semen parameters, body composition and glucose homeostasis, physical function, bone mineral density (BMD), anemia, as well as potential adverse effects. Results Twelve RCTs were included, with a total number of 645 patients. A total of 145 men were included in RCTs comparing AIs versus placebo or TRT and 476 men in RCTs with SERMs versus placebo or TRT. One RCT compared AIs versus SERMs in 24 men. Inclusion criteria were heterogenic. Most studies only included a small number of patients (range 11‐256) and follow‐up time was relatively short (6 weeks to 12 months). AIs as well as SERMs increased serum testosterone levels. Overall, there was no effect on sexual symptoms nor on semen parameters. Following aromatase inhibition, only minimal improvement of body composition and physical function was observed in some of the trials, but spinal BMD decreased. SERMs only induced a small improvement in body composition. The effect of SERMs on physical function and on BMD was not assessed. No major adverse effects occurred. Conclusion AIs are not recommended as treatment for functional hypogonadism because of insufficient efficacy as well as a decrease in BMD. SERMs might be an alternative for TRT, but more research is needed to evaluate their effect on hypogonadal signs and symptoms, as well as on their long‐term safety profile.

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“…A small decrease in BMI and waist circumference was seen in men with IGT 20. Furthermore, an increase was reported for lean body mass, fat‐free mass, and skeletal muscle mass 17…”

Section: Resultsmentioning

confidence: 99%

Aromatase inhibitors and selective estrogen receptor modulators: Unconventional therapies for functional hypogonadism?

2019

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“…A recent placebo-controlled trial on obese men, also showed beneficial effects of CC in increasing gonadotropins and testosterone levels, as well as improvements in body composition; however, estradiol levels increased from 32.5±12.6 to 89.4±47.8 pg/mL within three months of starting CC [7]. These findings show that CC treatment, although effective in increasing testosterone levels, can be associated with an unwanted increase in estradiol and hyperestrogenemic symptoms [7][8][9][10]18,19]. AI such as AZ are often employed to correct elevations in estradiol levels or low T/E ratios that can be associated with CC treatment [20].…”

Section: Discussionmentioning

confidence: 97%

“…Growing evidence suggests that CC is safe and effective for treating hypogonadism, particularly in young men [4,5]. However, CC treatment can cause increases in estradiol levels that may require the addition of AI in some patients [7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

“…The frequency of hyperestrogenemia and the factors predicting the need for AI therapy in the setting of CC monotherapy are unknown. Obesity is a risk factor for hypogonadism [11] and CC has been successfully used to increase testosterone levels in obese men but estrogen levels also increase [7,12]. Although the association between obesity and elevated estradiol levels seems intuitive given the presence of aromatase in adipose tissue, the evidence is inconsistent across studies [13].…”

Section: Introductionmentioning

confidence: 99%

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Obesity and Baseline Estradiol Levels Are Independent Predictors for Initiation of Anastrozole in Hypogonadal Men on Clomiphene Citrate

Keihani

Cheng

Stoddard

et al. 2020

World J Mens Health

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Purpose: To assess the conversion rate from clomiphene citrate (CC) monotherapy to combination CC+anastrozole (AZ) therapy in hypogonadal men and the predictors associated with the initiation of AZ. Materials and Methods: A retrospective review of records from hypogonadal men treated with CC in a single fertility center was performed from 2013 to 2018. Patient age, body mass index (BMI), blood pressure, and reproductive hormones were obtained at baseline. Obesity was defined as BMI≥30 kg/m 2. Cox proportional hazards models were used to identify predictors of switching to combination CC+AZ therapy. Results: A total of 318 men on CC were included. Median (interquartile range) age was 34 years (30-39 years) and patients were followed for a median of 9 months (4-17 months). Of these, 97 (30.5%) were started on CC+AZ therapy. These patients had higher baseline BMI and estradiol, which in multivariable regression were significant predictors for switching to CC+AZ therapy. A threshold of 18.5 pg/mL for baseline estradiol provided the highest accuracy for predicting the addition of AZ after adjusting for baseline BMI and total testosterone levels. Conclusions: In our practice, following CC monotherapy, 30% of men were initiated on CC+AZ. Obesity (BMI≥30 kg/m 2) and baseline estradiol ≥18.5 pg/mL can predict the conversion to combination therapy with addition of AZ. This information can be used to counsel patients and also help to identify patients who can be started on combination therapy upfront.

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“…38 This made clomiphene citrate a potential treatment for men with central hypogonadism including those with MOSH. 39 Nevertheless, there are no randomized trials to prove its safety and effi cacy in the management of central hypogonadism. 5 Regarding its use in men wishing to preserve fertility, most studies did not show improvement.…”

Section: ■ Case Resumed: Mosh Syndromementioning

confidence: 99%

An obese 48-year-old man with progressive fatigue and decreased libido

Farkouh

Zayed

2019

CCJM

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Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study

Cited by 40 publications

References 43 publications

Aromatase inhibitors and selective estrogen receptor modulators: Unconventional therapies for functional hypogonadism?

Aromatase inhibitors and selective estrogen receptor modulators: Unconventional therapies for functional hypogonadism?

Obesity and Baseline Estradiol Levels Are Independent Predictors for Initiation of Anastrozole in Hypogonadal Men on Clomiphene Citrate

An obese 48-year-old man with progressive fatigue and decreased libido

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