Introduction and Objectives - Enclomiphene, the trans diastereoisomer of clomifene, is a selective oestrogen receptor modulator (SERM) in the pituitary. Blocking the negative oestrogenic feedback results in increased luteinising hormone (LH) levels which then stimulate production of endogenous T. Exogenous T has been shown to reduce spermatogenesis which could be counterproductive in men wishing to preserve fertility. This study compares the impact of enclomiphene with one T gel on certain aspects of endocrine function and spermatogenesis.
Methods - A double-blind, placebo and active control study of two doses of enclomiphene (12.5 and 25 mg) with open-label on-demand T gel in 120 patients with secondary hypogonadism over a 3-month period. Men were 21-65 years and had not received exogenous T within the previous 6 months.
Results - All three active groups exhibited statistically significant increases (ng/dl) from baseline in T compared to placebo (Enclomiphene 12.5 mg 217-472; 25 mg 210 406: T gel 210-463: Placebo 214-199). Enclomiphene at both doses increased LH and follicle stimulating hormone (FSH) levels (mIU/ml) beyond baseline and placebo whereas T gel resulted in a >50% reduction in both pituitary hormones (LH Enclomiphene 12.5 mg 4.4-8.9; 25 mg 5.3-11.7: T gel 3.9-1.4: Placebo 3.9-3.7: FSH Enclomiphene 12.5 mg 6.4-11.5; 25 mg 9.4-14.1: T gel 6.0-2.9: Placebo 6.1-5.4). At baseline, the majority of men in all groups exhibited sperm concentrations above the World Health Organization (WHO) limit of normal (15 million sperm per ml of semen). This was maintained in the enclomiphene groups and the placebo group. However, in 13 out of 23 men in the T gel group the sperm concentration dropped below normal.
Conclusions - Enclomiphene acts at the level of the pituitary as a selective oestrogen receptor modulator to block the negative feedback of oestrogen on the pituitary hormones (LH and FSH). The present study shows that restoration of LH (secondary hypogonadal males having low levels) provides rapid and effective normalisation of T levels with no excursion into the supra-normal range. In addition, preservation of FSH levels in enclomiphene-treated patients ensures that there is no negative impact on sperm function. In contrast, the suppression of sperm function in the T gel group is likely to be a consequence of the observed reduction in FSH. Overall, this study shows that enclomiphene may provide effective therapy in men with secondary hypogonadism, particularly in those wishing to preserve fertility