Efficacy and safety of recombinant human follicle stimulating hormone (Gonal-F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men

Liu, Yang; Turner, Leo; Rushford, Debra; McDonald, Jillian; Baker, H. W. G.; Conway, Ann J.; Handelsman, David J.

doi:10.1093/humrep/14.6.1540

Cited by 106 publications

(68 citation statements)

References 40 publications

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“…The characteristics of the studies included in the meta-analysis are summarized in Table 1 (Scherman et al, 1964;Gayral et al, 1975;Burger & Baker, 1984;D'Agata et al, 1984;Gattuccio et al, 1984;Levalle et al, 1984;Abbaticchio et al, 1985;Ley & Leonard, 1985;Okuyama et al, 1986;Burris et al, 1988b;Liu et al, 1988a;Burger et al, 1990;Saal et al, 1991;Schopohl et al, 1991;Vicari et al, 1992;Lenzi et al, 1993;Schaison et al, 1993;Kung et al, 1994;Kliesch et al, 1994;Kirk et al, 1994;Fuse et al, 1996;Burgu es & Calder on, 1997;European Metrodin HP Study Group, 1998;Tachiki et al, 1998;Giagulli, 1999;Carani et al, 1999;Liu et al, 1999;Bouloux et al, 2002Bouloux et al, , 2003Miyagawa et al, 2005;Zorn et al, 2005;Bakircioglu et al, 2007;Homayoun et al, 2008;Efesoy et al, 2009;Matsumoto et al, 2009;Oldereid et al, 2010;Warne et al, 2009;Sinisi et al, 2010;Milsom et al, 2012;…”

Section: Spermatogenesis In Hhg Subjects Upon Gonadotropin Therapymentioning

confidence: 99%

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

et al. 2014

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SUMMARYA meta-analysis was performed to systematically analyse the results of gonadotropin and GnRH therapy in inducing spermatogenesis in subjects with hypogonadotropic hypogonadism (HHG) and azoospermia. An extensive Medline and Embase search was performed including the following words: 'gonadotropins' or 'GnRH', 'infertility', 'hypogonadotropic', 'hypogonadism' and limited to studies in male humans. Overall, 44 and 16 studies were retrieved for gonadotropin and GnRH therapy, respectively. Of those, 43 and 16 considered the appearance of at least one spermatozoa in semen, whereas 26 and 10 considered sperm concentration upon gonadotropin and GnRH, respectively. The combination of the study results showed an overall success rate of 75% (69-81) and 75% (60-85) in achieving spermatogenesis, with a mean sperm concentration obtained of 5.92 (4.72-7.13) and 4.27 (1.80-6.74) million/ mL for gonadotropin and GnRH therapy, respectively. The results upon gonadotropin were significantly worse in studies involving only subjects with a pre-pubertal onset HHG, as compared with studies involving a mixed population of pre-and post-pubertal onset [68% (58-77) vs. 84% (76-89), p = 0.011 and 3.37 (2.25-4.49) vs. 12.94 (8.00-17.88) million/mL, p < 0.0001; for dichotomous and continuous data, respectively]. A similar effect was observed also upon GnRH. No difference in terms of successful achievement of spermatogenesis and sperm concentration was found for different FSH preparations. Previous use of testosterone replacement therapy (TRT) did not affect the results obtained with gonadotropins. Finally, a higher success rate was found for subjects with lower levels of gonadotropins at the baseline and for those using both human chorionic gonadotropin and FSH. Gonadotropin therapy, even with urinary derivatives, is a suitable option in inducing/restoring fertility in azoospermic HHG subjects. Gonadotropins appear to be more efficacious in subjects with a pure secondary nature (low gonadotropins) and a post-pubertal onset of the disorder, whereas previous TRT does not affect outcome.

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Section: Spermatogenesis In Hhg Subjects Upon Gonadotropin Therapymentioning

confidence: 99%

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

et al. 2014

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“…Sex hormones in¯uence the development of prostate cancer, now the commonest cancer in men in some Western countries (Parkin et al 1992). Sex hormones also in¯uence a variety of other conditions in men, such as infertility (Kaiser et al 1988), low sperm count (Lee et al 1998;Liu et al 1999), and benign prostatic hyperplasia (Denis et al 1999). Diet-related changes in hormone metabolism may also be of interest to elite athletes, who may bene®t from maximising anabolic steroid production to enhance physical performance (Brotherhood, 1984;Miller & Wolfe, 1999).…”

Section: Introductionmentioning

confidence: 99%

The effects of diet on circulating sex hormone levels in men

Allen¹,

Key²

2000

Nutr. Res. Rev.

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There is considerable epidemiological evidence that a Western-style diet may increase the risk of certain hormone-dependent conditions in men via its effects on hormone metabolism. Experimental evidence also suggests that dietary factors may exert subtle effects on hormone metabolism. Here we review the clinical and epidemiological evidence that diet is associated with circulating sex hormone levels in men. In comparison with factors such as age and BMI, nutrients do not appear to be strong determinants of sex hormone levels. Dietary intervention studies have not shown that a change in dietary fat and/or dietary ®bre intake is associated with changes in circulating sex hormone concentrations over the short term. The data on the effects of dietary phyto-oestrogens on sex hormone levels in men are too limited for conclusions to be drawn. Observational studies between men from different dietary groups have shown that a vegan diet is associated with small but signi®cant increases in sex-hormone-binding globulin and testosterone concentrations in comparison with meat-eaters. However, these studies have not demonstrated that variations in dietary composition have any long-term important effects on circulating bioavailable sex hormone levels in men. This lack of effect may be partly explained by the body's negative feedback mechanism, which balances out small changes in androgen metabolism in order to maintain a constant level of circulating bioavailable androgens. It appears, therefore, that future studies should look for dietary effects on the feedback mechanism itself, or on the metabolism of androgens within the target tissues.

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“…Human menopausal gonadotrophin (HMG), a urine-derived source of FSH, has been shown to induce spermatogenesis in men with HH, but this preparation also contains LH, which adds a further variable in the treatment [30]. Additionally, the urinary gonadotropin preparations such as HMG had to be administered by intramuscular injection, but recombinant preparations are now available that can be self-administered by subcutaneous injection, with important implications for clinical management [24,[31][32][33].…”

Section: Managementmentioning

confidence: 99%

Management of Male Hypogonadotrophic Hypogonadism

2007

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THE development of sexual maturity and reproductive function in the male is dependent upon appropriate secretion of hormones that orchestrate the sophisticated relationship between the hypothalamus, pituitary, and testes -the hypothalamic-pituitary-gonadal (HPG) axis. A state of hypogonadism, i.e. inadequate testicular function, is manifested by deficiencies in secretion of androgens, with a wide range of effects on a number of physiological processes, including gametogenesis. Any dysfunction in the HPG axis can result in hypogonadotrophic hypogonadism, where a decrease in endocrine and/or gametogenic function of the testes results in retardation of puberty and reproductive insufficiency [1].The hypothalamus is the centre of the reproductive axis. Messages received from the central nervous system and from the gonads are integrated by the hypothalamus to regulate the production and secretion of gonadotrophin releasing hormone (GnRH), which is released in a pulsatile manner that is essential for stimulating the production and release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary. The anterior pituitary produces LH and FSH in response to pulses of GnRH stimulation, and in the male LH and FSH both bind to specific receptors on the Leydig and Sertoli cells within the testis. This stimulation regulates the release of androgens required for pubertal development, and subsequently for the initiation and maintenance of male reproductive function and spermatogenesis. Feedback mechanisms play an important role in maintaining the reproductive axis: testosterone inhibits LH secretion, and inhibin secreted by Sertoli cells regulates FSH secretion. A reduction in negative feedback results in an increased secretion of FSH, and, in a manner similar to that found in the female with diminished ovarian function, serum FSH levels in the male act as an indicator of germinal epithelial function in the testis [2,3].Episodic secretion of GnRH is an essential part of this process. The hypothalamic pituitary gonadal axis is first activated during the fetal/neonatal period, when an increase in testosterone stimulates completion of the inguinoscrotal phase of testicular descent and further growth of the penis. This is accompanied by a wave of Sertoli and germ cell proliferation in the testis. A second wave of increased HPG axis activity then occurs during the early stages of puberty, with a second wave of Sertoli cell proliferation. This wave of proliferation is followed by terminal differentiation, and Leydig cells begin to secrete testosterone, allowing the normal development of puberty [4].A disruption in any of these events, from fetal to adult life, can lead to hypogonadism, and this can be manifested in a wide variety of clinical symptoms, according to the time of onset and the severity of the resulting hormone deficiency. In many cases, the symptoms may not be recognised before puberty. Hypogonadism can be classified into three categories, which must be considered in establishing the diagnosis r...

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Efficacy and safety of recombinant human follicle stimulating hormone (Gonal-F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men

Cited by 106 publications

References 40 publications

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

The effects of diet on circulating sex hormone levels in men

Management of Male Hypogonadotrophic Hypogonadism

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