Alternatives to Testosterone Therapy: A Review

Lo, Eric M.; Rodríguez, Katherine; Khera, Mohit

doi:10.1016/j.sxmr.2017.09.004

Cited by 50 publications

(42 citation statements)

References 48 publications

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“…Mechanism of Action. SERMs and AIs are able to elicit the secretion of LH and FSH with different mechanism: a direct action at the hypothalamus (SERMs), where they block estrogen receptors (such as clomiphene citrate, CC), or an indirect one (AIs), decreasing plasma oestrogens levels via a block of aromatase [7]. LH acts, consequently, at the testes to increase T secretion, while FSH may positively coregulate Sertoli cells function and the spermatogenesis.…”

Section: Serms and Ais: Mechanism Of Action Andmentioning

confidence: 99%

“…Hence, according to the results obtained in infertile women treated with either selective estrogen receptor modulators (SERMs) (i.e., clomiphene citrate) or aromatase inhibitors (AIs) (i.e., anastrozole or letrozole), which proved to enhance the serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), men with secondary functional hypogonadism were treated with the same drugs in order to increase the endogenous T levels [6]. On the contrary, both SERMs and AIs maintain the fertility, avoiding the block of spermatogenesis, as TRT does [7,8].…”

Section: Introductionmentioning

confidence: 99%

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Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

Giagulli

Silvestrini

Bruno

et al. 2020

International Journal of Endocrinology

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Hypogonadotropic hypogonadism (HH) can be sustained by organic or functional alterations of the hypothalamic-pituitary-testicular axis. Functional HH is related to systemic alterations, such as obesity or chronic inflammatory diseases, but could contribute to a negative course of the illness. For such situation, according to results obtained in infertile women, the administration of selective estrogen receptor modulators (SERMs) has been proposed in males too, with positive results on both metabolic and sexual function. This class of medications increases gonadotropin levels via antagonism to the estrogenic receptor; similar biological effects are also exerted by aromatase inhibitors (AIs), despite different mechanism of action. After a brief review of trials regarding SERMs and AIs use in male HH, we describe the structure and function of the androgen receptor (AR) as a basis for clinical research about compounds able to bind to AR, in order to obtain specific effects (SARMs). The tissue selectivity and different metabolic fate in comparison to testosterone can potentiate anabolic versus androgenic effects; therefore, they might be a valid alternative to testosterone replacement therapy avoiding the negative effects of testosterone (i.e., on prostate, liver, and hematopoiesis). Trials are still at an early phase of investigation and, at the moment, the application seems to be more useful for chronic disease with catabolic status while the validation as replacement for hypogonadism requires further studies.

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Section: Serms and Ais: Mechanism Of Action Andmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

Giagulli

Silvestrini

Bruno

et al. 2020

International Journal of Endocrinology

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“…It also preserves endogenous testosterone production, since it does not suppress the hypothalamic-pituitary-testicular axis. 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.…”

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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“…Alternatives to testosterone therapy can be used to treat hypogonadism while preserving fertility in younger men [2]. Selective estrogen receptor modulators such as clomiphene citrate (CC) and aromatase inhibitors (AI) such as anastrozole (AZ), as well as human chorionic gonadotropin are commonly used for this purpose [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…In males, this can stimulate endogenous testosterone production [5] and a rising prevalence of CC usage in men has been reported in the USA [6]. 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%

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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Alternatives to Testosterone Therapy: A Review

Cited by 50 publications

References 48 publications

Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?

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

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

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