Awesome clarification! Thank you.
The relative roles of FSH and LH in the control of human spermatogenesis are not well established. We previously reported that supraphysiological doses of hCG can stimulate sperm production in gonadotropin-suppressed normal men despite prepubertal FSH levels. To determine whether more nearly physiological levels of human LH (hLH) also can stimulate spermatogenesis when FSH levels are suppressed, we administered hLH to normal men whose endogenous gonadotropin levels and sperm production were suppressed by exogenous testosterone enanthate (T). After a 3-month control period, 11 normal men received 200 mg T, im, weekly to suppress LH and FSH. T administration alone was continued for 3-4 months until 3 successive sperm concentrations (performed twice monthly) revealed azoospermia or severe oligospermia (sperm concentrations, less than 4 million/ml). Then, while continuing T, 4 of the 11 men (experimental subjects) simultaneously received 1100 IU hLH, sc, daily for 4-6 months to replace LH activity, leaving FSH activity suppressed. The effect on sperm production of the selective FSH deficiency produced by hLH plus T administration was determined. The remaining 7 men (control subjects) continued to receive T alone at the same dosage, without gonadotropin replacement, for an additional 6 months. In the four experimental subjects, sperm concentrations increased significantly from 0.7 +/- 0.7 million/ml (mean +/- SEM) during T treatment alone to 19 +/- 4 million/ml during hLH plus T administration (P less than 0.001). However, none of the men achieved sperm concentrations consistently in their own pretreatment range. Sperm motilities and morphologies were normal in all four subjects by the end of hLH plus T administration. In contrast, sperm concentrations in the seven control subjects remained suppressed (less than 3 million/ml) throughout the entire period of prolonged T administration alone. Serum LH bioactivity, determined monthly by in vitro mouse Leydig cell bioassay in all four experimental subjects, was markedly suppressed during T administration alone (120 +/- 10 ng/ml) compared to that during the control period (390 +/- 20 ng/ml; P less than 0.001). With the addition of hLH to T, LH bioactivity returned to control levels (400 +/- 40 ng/ml; P = NS compared to control value). Serum FSH levels determined monthly by RIA were reduced from 98 +/- 12 ng/ml during the control period to undetectable levels (less than 25 ng/ml) during the T alone and the hLH plus T periods (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
Early Experience With hMG in Combination With hCG Therapy
FSH has been used successfully for infertility treatment of patients with hypogonadotropic hypogonadism for more than 50 years, initially with urinary menopausal gonadotropins having FSH activity. It is worth reading the initial reports of FSH therapy in hypogonadotropic patients. MacLeod and coworkers reported on the successful therapy with urinary menopausal gonadotropins of a 37-year-old patient who underwent complete hypophysectomy in 1963 (10, 11). The patient had provided a semen sample 1 day before the hypophysectomy that showed 576 million sperm per ejaculate and quite good sperm motility and morphology. After surgery, the ejaculate quality decreased significantly and, following several weeks after hypophysectomy, the patient was unable to provide semen samples any more. Approximately 14 weeks after hypophysectomy, a bilateral testicular biopsy was performed which showed involution of spermatogenesis to the level of spermatogonia and only few areas with primary spermatocytes. One day after the first testicular biopsy, treatment with hMG (human menopausal gonadotropin originating from human urine with mainly FSH and some LH activity) was initiated in the patient, at a dose of approximately 206 I.U. per day.
After 64 days of menopausal gonadotropin treatment, another testicular biopsy only of the right testis revealed stimulated spermatogenesis, showing all stages of spermatogenesis including late elongated testicular spermatids. However, the restoration of spermatogenesis appeared only qualitatively normal, not quantitatively. As a patient was still unable to produce an ejaculate probably due to the insufficient low LH activity in the hMG preparation and therefore low testosterone serum levels, hCG therapy with 4000 I.U. on alternate days was added to stimulate testosterone production by the Leydig cells. At the same time the hMG dose of 206 I.U. was given no longer daily, but only every second day (alternating with hCG injections). With the combined therapy of hMG and hCG the patient regained the ability to produce an ejaculate that showed a total sperm count of several million with progressive sperm motility and normal sperm morphology, that were still decreased compared to the levels analyzed before hypophysectomy (11). Later the patient decided not to continue with hMG therapy and, unfortunately, no fertility data are available. However, this early comprehensive case report demonstrated clearly the principle of FSH therapy in combination with hCG for stimulation of spermatogenesis in patients with hypogonadotropic hypogonadism.