Clomiphene Citrate

[Michael Scally MD]

Baseline Gonadotropin Levels and Testosterone Response in Hypogonadal Men Treated with Clomiphene Citrate

Objective: To investigate the role of baseline gonadotropins in predicting the biochemical response to clomiphene citrate (CC) treatment.

Methods: We conducted a retrospective review of data from hypogonadal men treated with CC in two high-volume fertility centers between 2013 and 2018. Patient age, body mass index (BMI), and baseline hormones (follicle stimulating hormone [FSH], luteinizing hormone [LH], and total testosterone [TT]) were obtained. Response to treatment was measured as changes in TT levels within six months of initiating CC treatment. Linear regression models adjusted for age, BMI, and time on CC therapy were fitted to assess the associations between baseline LH and FSH levels with treatment response.

Results: A total of 332 men with mean ± standard deviation age of 36.2±8.2 years were included. Median time to initial follow-up was 6 weeks (25th-75th interquartile range [IQR]: 4-9 weeks). TT levels increased significantly on CC treatment (mean change: 329.2 ng/dL, 95% CI: 307.4 to 351.0) with 73% of men having at least 200 ng/dL increase over baseline TT levels. In univariable linear regression models, only age was significantly associated with TT response. Neither the baseline LH nor FSH significantly predicted TT response in linear regression models.

Conclusion: CC treatment results in significant increases in testosterone levels in most men. Baseline gonadotropins are not strong predictors for treatment response to CC. Adequate biochemical response with CC trial can be expected in most patients with normal or slightly elevated baseline gonadotropin levels.

Keihani S, Wright LN, Alder NJ, et al. Baseline gonadotropin levels and testosterone response in hypogonadal men treated with clomiphene citrate [published online ahead of print, 2020 Apr 27]. Urology. 2020;S0090-4295(20)30465-9. doi:10.1016/j.urology.2020.04.074 https://www.goldjournal.net/article/S0090-4295(20)30465-9/pdf

 

[RunTrenFckTens]

I wonder if a small dose of an AI would increase the TT even more. A 200ng/dL increase seems disappointing.

 

[Villain]

Baseline Gonadotropin Levels and Testosterone Response in Hypogonadal Men Treated with Clomiphene Citrate

Objective: To investigate the role of baseline gonadotropins in predicting the biochemical response to clomiphene citrate (CC) treatment.

Methods: We conducted a retrospective review of data from hypogonadal men treated with CC in two high-volume fertility centers between 2013 and 2018. Patient age, body mass index (BMI), and baseline hormones (follicle stimulating hormone [FSH], luteinizing hormone [LH], and total testosterone [TT]) were obtained. Response to treatment was measured as changes in TT levels within six months of initiating CC treatment. Linear regression models adjusted for age, BMI, and time on CC therapy were fitted to assess the associations between baseline LH and FSH levels with treatment response.

Results: A total of 332 men with mean ± standard deviation age of 36.2±8.2 years were included. Median time to initial follow-up was 6 weeks (25th-75th interquartile range [IQR]: 4-9 weeks). TT levels increased significantly on CC treatment (mean change: 329.2 ng/dL, 95% CI: 307.4 to 351.0) with 73% of men having at least 200 ng/dL increase over baseline TT levels. In univariable linear regression models, only age was significantly associated with TT response. Neither the baseline LH nor FSH significantly predicted TT response in linear regression models.

Conclusion: CC treatment results in significant increases in testosterone levels in most men. Baseline gonadotropins are not strong predictors for treatment response to CC. Adequate biochemical response with CC trial can be expected in most patients with normal or slightly elevated baseline gonadotropin levels.

Keihani S, Wright LN, Alder NJ, et al. Baseline gonadotropin levels and testosterone response in hypogonadal men treated with clomiphene citrate [published online ahead of print, 2020 Apr 27]. Urology. 2020;S0090-4295(20)30465-9. doi:10.1016/j.urology.2020.04.074 https://www.goldjournal.net/article/S0090-4295(20)30465-9/pdf

6 weeks follow up. How about 6 months follow up? Any studies done on that?

 

[Michael Scally MD]

A Paradoxical Decline in Semen Parameters in Men Treated with Clomiphene Citrate

Clomiphene, a selective oestrogen receptor modulator, has been utilised in managing male sub-fertility since 1967. Numerous controlled and uncontrolled studies have been published regarding the efficacy of clomiphene citrate in male sub-fertility cohorts.

Although the primary intention of treating men with clomiphene citrate is to improve sperm parameters and testosterone levels, some studies have reported paradoxical decline in semen parameters. The information available on decline in sperm parameters following treatment with clomiphene is sparse.

We conducted a systemic review using PubMed, Embase, Cochrane Library and Scopus databases for original studies reporting adverse effects of clomiphene citrate therapy on sperm parameters. This systematic review includes 384 men from 11 different studies that reported adverse effects of clomiphene citrate therapy.

Of the men included in these studies, 19%, 21%, 17% and 24% of clomiphene-treated men demonstrated a decrease in sperm count, concentration, motility and total motile sperm count respectively. In up to 17% of patients, deterioration of semen parameters did not recover following discontinuation of therapy. In the future, more studies should report on this aspect so the magnitude of this effect can be more clearly understood.

Gundewar T, Kuchakulla M, Ramasamy R. A paradoxical decline in semen parameters in men treated with clomiphene citrate: A systematic review. Andrologia. 2020 Oct 27:e13848. doi: 10.1111/and.13848. Epub ahead of print. PMID: 33108678. https://onlinelibrary.wiley.com/doi/10.1111/and.13848

 

[Michael Scally MD]

[OA] Converting Men from Clomiphene Citrate to Natesto for Hypogonadism Improves Libido, Maintains Semen Parameters, and Reduces Estradiol

Objective: To evaluate outcomes including libido, semen parameters, testosterone, estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) when converting men with low libido on Clomiphene Citrate (CC) to Natesto.

Methods: A retrospective chart review was performed. Baseline hormones prior to treatment, and again on CC and Natesto, as well as semen parameters on CC and on Natesto were assessed.

Results: In forty-one men, there was no difference in serum testosterone levels on CC versus Natesto, however; there was a significantly higher E2 on CC than on Natesto. Although FSH levels were significantly lower on Natesto than at baseline, the mean FSH level on Natesto remained in the normal reference range. There was no difference in LH levels at baseline versus on Natesto. There was not a significant difference in semen parameter values when men were on CC versus when they were on Natesto for 3 months. At 3 months after changing to Natesto, 38/41 (92.7%) men reported significantly improved libido on Natesto when compared to CC.

Conclusions: Men on CC and Natesto reach eugonadal testosterone levels, however; on CC the E2 level nearly doubled from baseline, and converting men from CC to Natesto returned E2 to nearly baseline levels. There was not a detrimental effect on semen parameters, and there was subjective reporting of improved libido after converting from CC to Natesto in this cohort, but further long-term studies are needed prior to Natesto being established as a definitive treatment for hypogonadism for men desiring to maintain fertility.

Kavoussi PK, Machen GL, Gilkey MS, et al. Converting men from Clomiphene Citrate to Natesto for hypogonadism improves libido, maintains semen parameters, and reduces estradiol. Urology. 2020 Dec 7:S0090-4295(20)31480-1. doi: 10.1016/j.urology.2020.11.047. Epub ahead of print. PMID: 33301741. https://www.goldjournal.net/article/S0090-4295(20)31480-1/fulltext

 

[RunTrenFckTens]

[OA] Converting Men from Clomiphene Citrate to Natesto for Hypogonadism Improves Libido, Maintains Semen Parameters, and Reduces Estradiol

Objective: To evaluate outcomes including libido, semen parameters, testosterone, estradiol (E2), follicle stimulating hormone (FSH), and luteinizing hormone (LH) when converting men with low libido on Clomiphene Citrate (CC) to Natesto.

Methods: A retrospective chart review was performed. Baseline hormones prior to treatment, and again on CC and Natesto, as well as semen parameters on CC and on Natesto were assessed.

Results: In forty-one men, there was no difference in serum testosterone levels on CC versus Natesto, however; there was a significantly higher E2 on CC than on Natesto. Although FSH levels were significantly lower on Natesto than at baseline, the mean FSH level on Natesto remained in the normal reference range. There was no difference in LH levels at baseline versus on Natesto. There was not a significant difference in semen parameter values when men were on CC versus when they were on Natesto for 3 months. At 3 months after changing to Natesto, 38/41 (92.7%) men reported significantly improved libido on Natesto when compared to CC.

Conclusions: Men on CC and Natesto reach eugonadal testosterone levels, however; on CC the E2 level nearly doubled from baseline, and converting men from CC to Natesto returned E2 to nearly baseline levels. There was not a detrimental effect on semen parameters, and there was subjective reporting of improved libido after converting from CC to Natesto in this cohort, but further long-term studies are needed prior to Natesto being established as a definitive treatment for hypogonadism for men desiring to maintain fertility.

Kavoussi PK, Machen GL, Gilkey MS, et al. Converting men from Clomiphene Citrate to Natesto for hypogonadism improves libido, maintains semen parameters, and reduces estradiol. Urology. 2020 Dec 7:S0090-4295(20)31480-1. doi: 10.1016/j.urology.2020.11.047. Epub ahead of print. PMID: 33301741. https://www.goldjournal.net/article/S0090-4295(20)31480-1/fulltext

Natesto... I have never even heard of that for treating hypogonadism. Looks like a better option down the road to avoid the clomid sides and keep fertility. I wonder what the cost is.