Prospects for FSH Treatment of Male Infertility

2020 ◽  
Vol 105 (7) ◽  
pp. 2105-2118
Author(s):  
Manuela Simoni ◽  
Giulia Brigante ◽  
Vincenzo Rochira ◽  
Daniele Santi ◽  
Livio Casarini

Abstract Context Despite the new opportunities provided by assisted reproductive technology (ART), male infertility treatment is far from being optimized. One possibility, based on pathophysiological evidence, is to stimulate spermatogenesis with gonadotropins. Evidence Acquisition We conducted a comprehensive systematic PubMed literature review, up to January 2020, of studies evaluating the genetic basis of follicle-stimulating hormone (FSH) action, the role of FSH in spermatogenesis, and the effects of its administration in male infertility. Manuscripts evaluating the role of genetic polymorphisms and FSH administration in women undergoing ART were considered whenever relevant. Evidence Synthesis FSH treatment has been successfully used in hypogonadotropic hypogonadism, but with questionable results in idiopathic male infertility. A limitation of this approach is that treatment plans for male infertility have been borrowed from hypogonadism, without daring to overstimulate, as is done in women undergoing ART. FSH effectiveness depends not only on its serum levels, but also on individual genetic variants able to determine hormonal levels, activity, and receptor response. Single-nucleotide polymorphisms in the follicle-stimulating hormone subunit beta (FSHB) and follicle-stimulating hormone receptor (FSHR) genes have been described, with some of them affecting testicular volume and sperm output. The FSHR p.N680S and the FSHB –211G>T variants could be genetic markers to predict FSH response. Conclusions FSH may be helpful to increase sperm production in infertile men, even if the evidence to recommend the use of FSH in this setting is weak. Placebo-controlled clinical trials, considering the FSHB-FSHR haplotype, are needed to define the most effective dosage, the best treatment length, and the criteria to select candidate responder patients.

Author(s):  
Ravi Kant ◽  
Mahendra Kumar Meena

Kisspeptin or GPR-54 is a product of KISS 1 gene regulating the production of gonadotropin releasing hormone (GnRH), luteinizing (LH) as well follicle stimulating hormone (FSH). Both LH and FSH are important hormones for reproduction in animals as well in humans. The recognition of Kisspeptin has a landmark bearing in reproductive biology. Few recent pilot studies have convincingly proven it to be a promising molecule in treating infertile couples especially those having hypogonadotropic hypogonadism not responding to conventional treatment.


2020 ◽  
Vol 9 (4) ◽  
pp. 1014 ◽  
Author(s):  
Daniele Santi ◽  
Pascale Crépieux ◽  
Eric Reiter ◽  
Giorgia Spaggiari ◽  
Giulia Brigante ◽  
...  

Background: Human reproduction is regulated by the combined action of the follicle-stimulating hormone (FSH) and the luteinizing hormone (LH) on the gonads. Although FSH is largely used in female reproduction, in particular in women attending assisted reproductive techniques to stimulate multi-follicular growth, its efficacy in men with idiopathic infertility is not clearly demonstrated. Indeed, whether FSH administration improves fertility in patients with hypogonadotropic hypogonadism, the therapeutic benefit in men presenting alterations in sperm production despite normal FSH serum levels is still unclear. In the present review, we evaluate the potential pharmacological benefits of FSH administration in clinical practice. Methods: This is a narrative review, describing the FSH physiological role in spermatogenesis and its potential therapeutic action in men. Results: The FSH role on male fertility is reviewed starting from the physiological control of spermatogenesis, throughout its mechanism of action in Sertoli cells, the genetic regulation of its action on spermatogenesis, until the therapeutic options available to improve sperm production. Conclusion: FSH administration in infertile men has potential benefits, although its action should be considered by evaluating its synergic action with testosterone, and well-controlled, powerful trials are required. Prospective studies and new compounds could be developed in the near future.


1991 ◽  
Vol 125 (3) ◽  
pp. 280-285 ◽  
Author(s):  
J. Alan Talbot ◽  
Ann Lambert ◽  
Robert Mitchell ◽  
Marek Grabinski ◽  
David C. Anderson ◽  
...  

Abstract We have investigated the role of Ca2+ in the control of FSH-induced estradiol secretion by Sertoli cells isolated from 8-10 days old rats. Exogenous Ca2+ (4-8 mmol/1) inhibited FSH-stimulated E2 secretion such that, with 8 mmol/l Ca2+ and FSH (8 IU/l) E2 secretion decreased from 2091±322 to 1480±84 pmol/l (p<0.002), whilst chelation of Ca2+ in the culture medium with EGTA (3 mmol/l) increased E2 secretion from 360±45 to 1242±133 pmol/l) in the absence of FSH. Further, EGTA (3 mmol/l) markedly potentiated FSH (8 IU/l), forskolin (1 μmol/l) and dibutyryl cAMP (1 mmol/l)-stimulated E2 secretion. Addition of the Ca2+ ionophores, ionomycin (2-5 μmol/l) and A23187 (2 μmol/l), inhibited FSH (8 IU/l)-stimulated E2 secretion by >80%. The effect of ionomycin was totally reversible, whereas that of A23187 was irreversible. Ionomycin (5 μmol/l) had no effect on EGTA-induced E2 secretion in the absence of FSH, but reduced EGTA-provoked E2 secretion by 59% in the presence of FSH (8 IU/l). Similarly, forskolin- and dibutyryl cAMP-provoked E2 production was inhibited 46-50% by ionomycin (5 μmol/l). We conclude that FSH-induced E2 secretion from immature rat Sertoli cells is modulated by intra- and extracellular Ca2+.


2008 ◽  
Vol 70 (2) ◽  
pp. 266-272 ◽  
Author(s):  
Richard J. Kline ◽  
Izhar A. Khan ◽  
Kiyoshi Soyano ◽  
Megumi Takushima

1990 ◽  
Vol 122 (1) ◽  
pp. 96-100 ◽  
Author(s):  
Ulrich Fingscheidt ◽  
Gerhard F. Weinbauer ◽  
Shafiq A. Khan ◽  
Eberhard Nieschlag

Abstract. Three adult rhesus monkeys were injected intramuscularly with human FSH at doses of 2, 10 or 25 IU/kg in a cross-over design with 3-week intervals between injections. On each occasion a fourth animal received saline only as control. Serum levels of exogenous FSH were monitored by a fluoroimmunoassay specific for human FSH. Serum inhibin was measured by a heterologous radioimmunoassay. Each FSH injection was followed by a rise in serum inhibin in a dose-dependent manner. The half-life of human FSH in rhesus monkeys ranged from 25.1 to 32.9 h with no significant differences between doses. The rise of inhibin occurred with a lag time of 53.3 to 61.9 h after injection of FSH, independent of the dose administered. These findings support the concept that inhibin secretion in male primates is stimulated by FSH.


1996 ◽  
Vol 271 (52) ◽  
pp. 33317-33324 ◽  
Author(s):  
Tamara L. Goetz ◽  
Tracy L. Lloyd ◽  
Michael D. Griswold

1974 ◽  
Vol 75 (3) ◽  
pp. 491-496 ◽  
Author(s):  
Junichi Mori ◽  
Hiroshi Nagasawa ◽  
Reiko Yanai ◽  
Junji Masaki

ABSTRACT The sequence of changes in the serum levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from 2 days before to 24 h after parturition of primiparous Sprague-Dawley rats was investigated by radioimmunoassay. No appreciable change in average serum FSH levels was observed during 2 days before and 1 h after parturition. After this the levels increased gradually to show a peak at 7 h after parturition and then declined gradually until 24 h after parturition. However, the level at 24 h after parturition was still twice as high as that at parturition (0 h). The average serum LH levels which were low between 2 days before and 1 h after parturition, showed a peak at 7 h and decreased toward 13 h after parturition. The same levels as at parturition were maintained between 13 and 24 h after parturition. The time of surge of either FSH or LH was closely related to the time after parturition. There were some differences between FSH and LH in the patterns of sequence of changes in the serum levels near parturition.


2018 ◽  
Vol 23 ◽  
pp. 2515690X1879605 ◽  
Author(s):  
Nourollah Rezaei ◽  
Tahereh Mardanshahi ◽  
Majid Malekzadeh Shafaroudi ◽  
Saeed Abedian ◽  
Hamid Mohammadi ◽  
...  

The present study was designed to investigate the antioxidant property of l-carnitine (LC) on serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TH) and testis oxidative stress in streptozotocin (STZ)-induced diabetic rats. The rats were divided into the following groups: group I, control; group II, LC 100 mg/kg/d; group III, diabetic; and groups IV to VI, diabetic rats treated with 50, 100, and 200 mg/kg/d of LC, respectively. Daily injections were given intraperitoneally for 7 weeks. At the end of experimental period, after sacrificing the rats, FSH, LH, TH, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), mitochondrial function (MTT), protein carbonyl (PC), and reactive oxygen species (ROS) levels were measured. STZ caused an elevation of MDA, ROS, and PC ( P < .001) with reduction of GSH, CAT, TAC, and MTT ( P < .001) in the serum levels. Group VI had significantly increased FSH, LH, and TH levels versus the untreated diabetic group ( P < .001). Although groups V and VI significantly decreased MDA ( P < .001), PC ( P < .01), and ROS ( P < .01) compared with the untreated diabetic group; only in group VI, the activity of GSH ( P < .001), CAT ( P < .01), TAC ( P < .001), and MTT ( P < .001) significantly increased. The results of the present study suggest that LC decreased diabetes-induced oxidative stress complications and also improved serum level of FSH, LH, and TH by reducing levels of lipid peroxidation and increasing antioxidant enzymes.


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