Oral Enclomiphene Citrate Stimulates the Endogenous Production of Testosterone and Sperm Counts in Men with Low Testosterone: Comparison with Testosterone Gel

Abstract

Introduction Clomiphene citrate is employed off-label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism. Aim Our aim was to compare oral enclomiphene citrate as an alternative to topical testosterone. Main Outcome Measures Blood levels of total testosterone (TT), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin-like growth factor 1 IGF-1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated. Methods This was a proof-of-principle, randomized, open-label, fixed dose, active-control, two-center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone. Results After discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75–334 × 106/mL range. The gel was ineffective in raising sperm counts above 20 × 106/mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow-up, only enclomiphene citrate treatment was associated with elevated sperm counts. Conclusions Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic–pituitary–testicular axis.

Clomiphene citrate treatment for late onset hypogonadism: rise and fall

“…Finally, CC represents a good alternative to TRT with the advantage of not blocking HPT axis, but taking into account our results and previous series (23, 25), it should be discussed with the patient that treatment will be permanent in most cases.…”

“…On the other hand, Kaminetsky and cols, and Wiehle and cols. reported that in patients with secondary hypogonadism who responded to EC therapy, once the treatment was stopped TT levels decreased and returned to the pre-treatment values (23, 25). Our results concur with the last two authors since all patients decreased TT levels 3 months after discontinuation of CC treatment, 78% of them under the normal range.…”

“…Even an isomer of CC, Enclomiphene (EC), has been introduced recently, having the advantages of shorter half-life and theoretically more specificity to increase LH and FSH (22). EC has also demonstrated to increase testosterone levels in a high proportion of cases (23). So if CC or EC are such a good treatment, why not use it in all cases?…”

Przewlekła ekspozycja na hałas a niedobór testosteronu — metaanaliza i metaregresja wyników badań na gryzoniach

“…It is associated with sexual dysfunction and decreased fertility, cardiovascular and metabolic disorders, low bone mineral density, obesity, psychosocial and cognitive dysfunction among other chronic complications [2]. Four to five million men in the United States alone are testosterone (T) deficient [3], and about 20% of all infertility cases can be accounted for by the male factor, with an additional 30-40% which can be attributed to both male and female factors [4,5]. It has been projected that in years to come the Western world will face an increasing burden of male HG [6].…”

Treatment of hypogonadotropic male hypogonadism: Case-based scenarios

“…In a randomized study by Kaminetsky et al [21] , the investigators compared levels of testosterone, FSH, and LH after hypogonadal males used either oral enclomiphene citrate or testosterone gel. Twelve male subjects were assigned to either of the two treatments.…”