Reinitiation of sperm production in gonadotropin-suppressed normal men by administration of follicle-stimulating hormone

Abstract

A B S T R A C T The specific roles of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in controlling human spermatogenesis are poorly understood. We studied the effect of an experimentally induced, selective LH deficiency on sperm production in normal men. After a 3-mo control period, five men received 200 mg testosterone enanthate (T) i.m./wk to suppress LH, FSH, and sperm counts. Then, while continuing T at the same dosage, human FSH (hFSH) was administered simultaneously to replace FSH activity, leaving LH activity suppressed. Four men received 100 IU hFSH s.c. daily plus T (high dosage hFSH) for 13-14 wk, while one man received 50 IU hFSH s.c. daily plus T (low dosage hFSH) for 5 mo. The effect on sperm production of the selective LH deficiency produced by hFSH plus T administration was assessed.In the four men who received the high dosage hFSH regimen, sperm counts were markedly suppressed during T administration alone (0.3±0.2 million/cm3, mean±SE, compared with 94±12 million/cm3 during the control period). Serum LH bioactivity (determined by in vitro mouse Leydig cell assay) was suppressd (140±7 ng/ml compared with 375±65 ng/ml during control period) and FSH levels (by radioimmunoassay) were reduced to undetectable levels (<25 ng/ml, compared with 98±21 ng/ml during control period) during T alone. With the addition of 100 IU hFSH s.c. daily to T, sperm counts increased significantly in all subjects (33±7 million/cm3, P < 0.02 compared with T alone). However, no subject consistently achieved sperm counts within his control range. Sperm morphology and motility were normal in all four men and in vitro sperm penetration of hamster ova was normal in the two men tested during the hFSH-plus-T period. During high-dosage hFSH administration, serum FSH levels increased to 273±44 ng/ml (just above the normal range for FSH, 30-230 ng/ml). Serum LH bioactivity was not significantly changed compared with the Talone period (147±9 ng/ml). After the hFSH-plus-T period, all four men continued to receive T alone after hFSH was stopped. Sperm counts were again severely suppressed (0.2±0.1 million/cm3), demonstrating the dependence of sperm production on hFSH administration.Serum T and estradiol (E2) levels increased two-to threefold during T administration alone compared with the control period. Both T and E2 levels remained unchanged with the addition of hFSH to T, confirming the lack of significant LH activity in the hFSH preparation.In the one man who received low dosage hFSH treatment, sperm counts were reduced to severely oligospermic levels, serum FSH was suppressed to undetectable levels, and serum LH bioactivity was markedly lowered during the T-alone period. With the addition of 50 IU hFSH s.c. daily to T, sperm counts increased, to a mean of 11±3 million/cm3. During this period, serum FSH levels increased to a mean of 105±11 ng/ml (slightly above this man's control range and within the normal adult range), while LH bioactivity remain suppressed. After hFSH was stopped and T alone was continued, sper...

The Relative Roles of Follicle-Stimulating Hormone and Luteinizing Hormone in Maintaining Spermatogonial Maturation and Spermiation in Normal Men

“…After treatment with T, 200 mg im weekly, and the induction of oligoazoospermia, hCG (5000 IU im three times weekly) (2,4) or pituitary-derived LH (1100 IU sc daily) (17) was found to restore sperm concentration partially. In a similar study, suppression of serum LH and selective FSH replacement (100 IU sc daily) also partially restored sperm concentration (1). In such studies, the complete elimination of one or other gonadotropin cannot be assured, but such data support the contention that both FSH and LH/intratesticular androgens are needed for quantitatively normal spermatogenesis to occur.…”

“…I N MAN, BOTH gonadotropins are required to reinitiate and maintain quantitatively normal sperm production after experimentally induced oligoazoospermia (1)(2)(3)(4). However, the relative roles of FSH and LH/intratesticular androgens on germ cell development remain unclear.…”

Pubertal induction in hypogonadism: Current approaches including use of gonadotrophins

“…In this setting, the use of hCG, as an LH substitute, will partially restore spermatogenesis [85,86] as will FSH, but combined action of both will fully restore sperm output.…”

Analysis of the Testicular Phenotype of the Follicle-Stimulating Hormone β-Subunit Knockout and the Activin Type II Receptor Knockout Mice by Stereological Analysis*

“…Using hpg mice, which, due to the failure of GnRH secretion by the hypothalamus, have undetectable levels of FSH and LH, Singh et al (11) showed that spermatogenesis could be initiated and maintained by the use of high doses of exogenous T. Although the mice treated in this manner were fertile, their testes were smaller than those of normal controls, and the numbers of testicular spermatids were decreased. However, other studies using passive immunization against FSH (5) in the rat have supported a role for FSH during spermatogenesis.In the human, several studies have emphasized the importance of FSH in the stimulation of spermatogenesis in some men with hypogonadotropic hypogonadism as well in the restoration of spermatogenesis in normal men in whom spermatogenesis had been suppressed by testosterone treatment (12)(13)(14).In a more specific approach to the removal of FSH, Kumar et al (15) used targeted disruption of the gene encoding the ␤-subunit of FSH in mice. They showed that male mice were fertile, and spermatogenesis proceeded successfully to completion.…”