Sex drive in hypogonadal men better on nasal testosterone vs clomiphene

For men with hypogonadism, switching from clomiphene citrate (CC) to nasal testosterone boosts sex drive and normalizes oestradiol (E2) levels without having any detrimental effects on semen parameters, as shown in a study.

“The current study suggests that [nasal testosterone] is an alternative treatment for hypogonadal men desiring to maintain fertility potential in a manner that optimizes libido response and minimizes aromatization of testosterone to estradiol (E2),” according to the investigators.

To assess the impact of converting to nasal testosterone, the investigators reviewed the medical records of 41 men (mean age, 38 years; mean body mass index, 31.2 kg/m²) who experienced low libido on CC. All men had their semen evaluated 3 months after changing treatments.

Serum testosterone levels on CC vs nasal testosterone were similar (p=0.842), but E2 levels were significantly higher on CC (p=0.0001). Follicle stimulating hormone (FSH) levels remained in the normal range on nasal testosterone, and there was no significant change seen in luteinizing hormone (LH) levels relative to baseline (p=0.178). [Urology 2020;doi:10.1016/j.urology.2020.11.047]

“The cohort in this current study showed similar improvements in serum testosterone levels to eugonadal levels as previously published studies on CC,” the investigators noted. [J Urol 2017;197:1127-1131; BJU Int 2012;110:1524-1528; J Sex Med 2010;7:269-276; Andrologia 2019;51:e13257; Sex Med Rev 2019;7:272-276]

When comparing between CC and nasal testosterone, there were no significant differences seen in semen volume (p=0.085), sperm concentration (p=0.322), percent sperm total motility (p=0.646), percent forward progressive motility (p=0.226), percentage of sperm with normal morphology by strict Kruger morphology criteria (p=0.873), and total motile sperm counts (p=0.289).

At 3 months after the switch to nasal testosterone, 38 out of 41 patients (92.7 percent) reported significantly boosted libido when compared with CC. There were no identifiable similarities among the three men who did not show improvement.

“There has been a rise in the prevalence of low testosterone in adolescents and young adults, for whom current or future fertility potential may be important. Long-acting traditional testosterone replacement therapy modalities, such as transdermal gels and intramuscular injections, suppress the gonadotropins FSH and LH, thereby suppressing spermatogenesis downstream by decreasing intratesticular testosterone levels,” the investigators pointed out. [Transl Androl Urol 2013;2:106-113; Endocr Rev 2002;23:735-762]

In the current study, the lower levels of normal for FSH and LH were 1.5 IU/L and 1.2 IU/L, respectively. While on nasal testosterone, seven men had FSH levels <1.5 IU/L, and a single man had LH suppressed <1.2 IU/L.

“Although some men did suppress gonadotropins below the laboratory reference range cutoff for low, the majority did not, and of those who did, the gonadotropins remained detectable. Having less profound LH suppression likely accounts for the maintenance of spermatogenesis even in these men, by allowing for intratesticular testosterone production to continue,” the investigators explained.

They recommended that clinicians offering nasal testosterone as a treatment for hypogonadal men closely monitor gonadotropins and semen parameters to confirm that they are being maintained.

Long-term studies are needed prior to establishing nasal testosterone as a definitive treatment for hypogonadism, especially in men who want to maintain fertility, the investigators said.