madman
Super Moderator
Abstract
Objective
To report a case of a testosterone deficient man desiring maintenance of spermatogenesis converting from clomiphene citrate (CC) to Natesto, who had a decrease in gonadotropins and semen parameter values after making this medication change. The data on men maintaining gonadotropins and semen parameter values after converting from CC to Natesto is also reported.
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
A 32-year-old testosterone deficient man desiring to maintain future fertility potential had a poor symptomatic response to CC despite adequate serum testosterone the response was converted to Natesto 11 mg twice daily. His gonadotropins diminished as did his semen parameter values but with dose titration of Natesto to 11 mg in the morning and 5.5 mg in the evening he had normalization of gonadotropins and a rise in semen parameter values back towards his values on CC with a continued satisfactory symptomatic response. The remainder of the 49 men to date converting from CC to Natesto revealed stability in gonadotropins and semen parameter values.
Conclusions
Testosterone deficient men interested in maintaining spermatogenesis who convert from CC to Natesto seeking a more robust symptomatic response should be followed closely with repeat serum gonadotropins and semen parameters to confirm that spermatogenesis is not being suppressed. Dose titration of Natesto may be effective at optimizing gonadotropins, semen parameter values, testosterone levels, and symptomatic response to treatment.
Introduction
The gonadotropins follicle-stimulating hormones (FSH) and luteinizing hormone (LH) which are responsible for signaling the testes for spermatogenesis and testosterone production respectively, are suppressed with long-acting traditional modalities of testosterone replacement therapy (TRT) such as transdermal gels and intramuscular injections, and thereby suppress spermatogenesis by decreasing intratesticular testosterone levels.1-3
Historically, clomiphene citrate (CC) has been prescribed off-label which inhibits estradiol (E2) negative feedback to the hypothalamus increasing LH secretion, stimulating testicular Leydig cells to increase testosterone production in a manner that maintains spermatogenesis.4 Although the majority of men treated with CC have normalization of their serum testosterone levels, E2 levels tend to rise, and symptomatic response to CC has been reported to be less optimal than on TRT, especially libido.5,6
The short-acting intranasal TRT, Natesto, allows for maintenance of FSH and LH within normal ranges in most men. Natesto has also been shown to allow for maintenance of spermatogenesis when given to TRT naïve patients or after a washout period from other TRT modalities in most men. 6,7
Discussion
In this study, although the majority of men (49/50, 98%) who converted from CC to Natesto maintained normal gonadotropin levels and stable semen parameter values, an exception to the rule has been demonstrated. Therefore, it is recommended that men being treated with Natesto for testosterone deficiency with a goal of maintaining spermatogenesis have gonadotropins and semen parameter values followed closely to confirm stability. In some cases, Natesto dose titration may allow for the return of gonadotropins and semen parameter values while maintaining a positive symptomatic response.
It was noted in this patient's case that when his semen parameter values decreased on Natesto 11 mg twice daily, he declined the option of changing back to CC despite the diminishment in semen parameter values.
This speaks to the significance of the difference in symptomatic response on TRT versus CC, which is a common clinical finding. Fortunately, in this individual’s case, dose titration was adequate to maintain his symptomatic response, maintain his gonadotropins, and his semen parameter values.
Our previous study evaluating outcomes in 41 men converting from CC to Natesto only revealed a statistically significant difference in E2 and FSH levels between the 2 treatments. The difference in E2 was quite significant as an advantage of Natesto. Although the difference in FSH levels did reveal a statistically significant difference, on Natesto FSH levels remained in the low normal range by reference range allowing for the maintenance of intratesticular testosterone levels by continued LH secretion resulting in maintenance of spermatogenesis.6 Although the purpose of this current study was to report on the individual patient who demonstrated suppression of gonadotropins and spermatogenesis on Natesto twice-daily dosing, the data on a total of 49 men who maintained spermatogenesis with the conversion from CC to Natesto was brought up to date, and a statistically significant difference was again noted in E2 levels, confirming the advantage of lower E2 levels on Natesto over CC. A statistically significant difference in semen volume was also demonstrated on CC (2.9 ± 1.3 mL) versus on Natesto (2.6 ± 1.3 mL). However, both means are well within normal ranges for semen volume and it is arguable if this represents a clinically significant difference, and there is no difference in total motile sperm counts on either treatment indicating that this change in semen volume would not be likely to impact fertility treatment options if needed.
Conclusions
Testosterone deficient men who are interested in maintaining spermatogenesis who convert from CC to Natesto seeking a more robust symptomatic response should be followed closely with repeat FSH and LH levels as well as semen parameter values to confirm that spermatogenesis is not being suppressed. Dose titration of Natesto may be effective at optimizing gonadotropins, semen parameter values, testosterone levels, and symptomatic response to treatment.
Objective
To report a case of a testosterone deficient man desiring maintenance of spermatogenesis converting from clomiphene citrate (CC) to Natesto, who had a decrease in gonadotropins and semen parameter values after making this medication change. The data on men maintaining gonadotropins and semen parameter values after converting from CC to Natesto is also reported.
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
A 32-year-old testosterone deficient man desiring to maintain future fertility potential had a poor symptomatic response to CC despite adequate serum testosterone the response was converted to Natesto 11 mg twice daily. His gonadotropins diminished as did his semen parameter values but with dose titration of Natesto to 11 mg in the morning and 5.5 mg in the evening he had normalization of gonadotropins and a rise in semen parameter values back towards his values on CC with a continued satisfactory symptomatic response. The remainder of the 49 men to date converting from CC to Natesto revealed stability in gonadotropins and semen parameter values.
Conclusions
Testosterone deficient men interested in maintaining spermatogenesis who convert from CC to Natesto seeking a more robust symptomatic response should be followed closely with repeat serum gonadotropins and semen parameters to confirm that spermatogenesis is not being suppressed. Dose titration of Natesto may be effective at optimizing gonadotropins, semen parameter values, testosterone levels, and symptomatic response to treatment.
Introduction
The gonadotropins follicle-stimulating hormones (FSH) and luteinizing hormone (LH) which are responsible for signaling the testes for spermatogenesis and testosterone production respectively, are suppressed with long-acting traditional modalities of testosterone replacement therapy (TRT) such as transdermal gels and intramuscular injections, and thereby suppress spermatogenesis by decreasing intratesticular testosterone levels.1-3
Historically, clomiphene citrate (CC) has been prescribed off-label which inhibits estradiol (E2) negative feedback to the hypothalamus increasing LH secretion, stimulating testicular Leydig cells to increase testosterone production in a manner that maintains spermatogenesis.4 Although the majority of men treated with CC have normalization of their serum testosterone levels, E2 levels tend to rise, and symptomatic response to CC has been reported to be less optimal than on TRT, especially libido.5,6
The short-acting intranasal TRT, Natesto, allows for maintenance of FSH and LH within normal ranges in most men. Natesto has also been shown to allow for maintenance of spermatogenesis when given to TRT naïve patients or after a washout period from other TRT modalities in most men. 6,7
Discussion
In this study, although the majority of men (49/50, 98%) who converted from CC to Natesto maintained normal gonadotropin levels and stable semen parameter values, an exception to the rule has been demonstrated. Therefore, it is recommended that men being treated with Natesto for testosterone deficiency with a goal of maintaining spermatogenesis have gonadotropins and semen parameter values followed closely to confirm stability. In some cases, Natesto dose titration may allow for the return of gonadotropins and semen parameter values while maintaining a positive symptomatic response.
It was noted in this patient's case that when his semen parameter values decreased on Natesto 11 mg twice daily, he declined the option of changing back to CC despite the diminishment in semen parameter values.
This speaks to the significance of the difference in symptomatic response on TRT versus CC, which is a common clinical finding. Fortunately, in this individual’s case, dose titration was adequate to maintain his symptomatic response, maintain his gonadotropins, and his semen parameter values.
Our previous study evaluating outcomes in 41 men converting from CC to Natesto only revealed a statistically significant difference in E2 and FSH levels between the 2 treatments. The difference in E2 was quite significant as an advantage of Natesto. Although the difference in FSH levels did reveal a statistically significant difference, on Natesto FSH levels remained in the low normal range by reference range allowing for the maintenance of intratesticular testosterone levels by continued LH secretion resulting in maintenance of spermatogenesis.6 Although the purpose of this current study was to report on the individual patient who demonstrated suppression of gonadotropins and spermatogenesis on Natesto twice-daily dosing, the data on a total of 49 men who maintained spermatogenesis with the conversion from CC to Natesto was brought up to date, and a statistically significant difference was again noted in E2 levels, confirming the advantage of lower E2 levels on Natesto over CC. A statistically significant difference in semen volume was also demonstrated on CC (2.9 ± 1.3 mL) versus on Natesto (2.6 ± 1.3 mL). However, both means are well within normal ranges for semen volume and it is arguable if this represents a clinically significant difference, and there is no difference in total motile sperm counts on either treatment indicating that this change in semen volume would not be likely to impact fertility treatment options if needed.
Conclusions
Testosterone deficient men who are interested in maintaining spermatogenesis who convert from CC to Natesto seeking a more robust symptomatic response should be followed closely with repeat FSH and LH levels as well as semen parameter values to confirm that spermatogenesis is not being suppressed. Dose titration of Natesto may be effective at optimizing gonadotropins, semen parameter values, testosterone levels, and symptomatic response to treatment.
