{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T19:19:24Z","timestamp":1783451964639,"version":"3.55.0"},"reference-count":32,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":97,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                    <jats:p\/>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Male hypogonadotropic hypogonadism is characterized by deficient secretion of luteinizing hormone and follicle-stimulating hormone, leading to low testosterone levels, impaired spermatogenesis, and often infertility. Treatment aims to normalize testosterone and induce spermatogenesis, with gonadotropin therapy as standard. Factors affecting treatment success and optimal duration remain unclear. This single-center retrospective cohort study assessed the outcomes of gonadotropin therapy in men with hypogonadotropic hypogonadism and azoospermia. Men \u2265 18 years were included. The primary outcome was the successful induction of spermatogenesis. Data on demographics, treatment regimens, semen parameters, pregnancy outcomes, and side effects were collected. Regression analyses identified factors associated with treatment success. Thirty-five men were included. Spermatogenesis was achieved in 74% of patients, with higher success rates in those receiving combined human chorionic gonadotropin and follicle-stimulating hormone therapy (78%) versus human chorionic gonadotropin monotherapy (33%). Of those producing sperm, 69% upgraded to a higher WHO semen category, with 29% reaching normospermia. The median maximum sperm concentration achieved during treatment was 8.3 million\/mL (IQR: 1.9\u201336.3). A larger baseline testicular volume was associated with a higher success rate of spermatogenesis and a shorter time to pregnancy. Pregnancy was achieved in 68% of patients, with 39% through spontaneous conception. The median time to first spermatogenesis was 7 months and to pregnancy was 21 months. Mild side effects occurred in 16% of patients. Gonadotropin therapy is effective and well tolerated in inducing spermatogenesis and achieving pregnancy in azoospermic men with HH. These findings, based on a contemporary Western cohort, provide updated evidence that supports personalized counseling and underscore the importance of long-term treatment adherence for successful fertility restoration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>Some men are infertile because their brain does not produce the hormones needed to make sperm. This condition is called hypogonadotropic hypogonadism. These men often have low testosterone and no sperm in their semen. In this study, we looked at whether hormone treatment could help these men produce sperm and have children. We studied 35 men who were given hormone injections at a Dutch university hospital. After treatment, 74% of them started producing sperm. Those who received a combination of two hormones had better results than those who received only one. Almost 70% of men with sperm had better sperm quality, and over a quarter reached normal sperm levels. Two-thirds of men who wanted children became fathers, mostly through natural conception. Our findings show that hormone treatment is safe and often successful. This can offer hope to men with this condition who want to become fathers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/raf-25-0100","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T17:51:26Z","timestamp":1779817886000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-13","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic benefits of gonadotropins in male hypogonadotropic hypogonadism: a focus on spermatogenesis and fertility"],"prefix":"10.1530","volume":"7","author":[{"given":"M","family":"Huijben","sequence":"first","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M A","family":"Prinsen","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C E","family":"de Keyser","sequence":"additional","affiliation":[{"name":"2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S M","family":"van der Leij","sequence":"additional","affiliation":[{"name":"2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E F H I","family":"Peeters","sequence":"additional","affiliation":[{"name":"2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A M E","family":"Stades","sequence":"additional","affiliation":[{"name":"2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S J","family":"Tanahatoe","sequence":"additional","affiliation":[{"name":"3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L M O","family":"de Kort","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H M K","family":"van Breda","sequence":"additional","affiliation":[{"name":"1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"2026070714152439600_bib1","first-page":"113","article-title":"Gonadotropins in infertile men with idiopathic hypogonadotropic hypogonadism","volume":"2","author":"Abbasi","year":"2008","journal-title":"Int J Fertil Sterility"},{"key":"2026070714152439600_bib2","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1093\/ejendo\/lvad166","article-title":"Gonadotropins for pubertal induction in males with hypogonadotropic hypogonadism: systematic review and meta-analysis","volume":"190","author":"Alexander","year":"2024","journal-title":"Eur J Endocrinol"},{"key":"2026070714152439600_bib3","first-page":"3341","article-title":"Serum inhibin B levels reflect Sertoli cell function in normal men and men with testicular dysfunction","volume":"81","author":"Anawalt","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070714152439600_bib4","first-page":"339","article-title":"Gonadotropin treatment of hypogonadotropic hypogonadal adolescents","volume":"12","author":"Bouvattier","year":"1999","journal-title":"J Pediatr Endocrinol Metab"},{"key":"2026070714152439600_bib5","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nrendo.2011.164","article-title":"Neonatal gonadotropin therapy in male congenital hypogonadotropic hypogonadism","volume":"8","author":"Bouvattier","year":"2012","journal-title":"Nat Rev Endocrinol"},{"key":"2026070714152439600_bib6","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1093\/humrep\/12.5.980","article-title":"Subcutaneous self-administration of highly purified follicle-stimulating hormone and human chorionic gonadotrophin for the treatment of male hypogonadotrophic hypogonadism","volume":"12","author":"Burgu\u00e9s","year":"1997","journal-title":"Hum Reprod"},{"key":"2026070714152439600_bib7","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jsxm.2020.01.011","article-title":"Correlations among genotype and outcome in Chinese male patients with congenital hypogonadotropic hypogonadism under hCG treatment","volume":"17","author":"Chen","year":"2020","journal-title":"J Sex Med"},{"key":"2026070714152439600_bib8","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1007\/s10815-021-02211-3","article-title":"Reproductive outcomes of microdissection testicular sperm extraction in hypogonadotropic hypogonadal azoospermic men after gonadotropin therapy","volume":"38","author":"Chen","year":"2021","journal-title":"J Assist Reprod Genet"},{"key":"2026070714152439600_bib9","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/humupd\/dmp048","article-title":"World Health Organization reference values for human semen characteristics","volume":"16","author":"Cooper","year":"2009","journal-title":"Hum Reprod Update"},{"key":"2026070714152439600_bib10","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1530\/eje.0.1470617","article-title":"Maintenance of spermatogenesis in hypogonadotropic hypogonadal men with human chorionic gonadotropin alone","volume":"147","author":"Depenbusch","year":"2002","journal-title":"Eur J Endocrinol"},{"key":"2026070714152439600_bib11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.beem.2014.10.005","article-title":"Gonadotrophin replacement for induction of fertility in hypogonadal men","volume":"29","author":"Dwyer","year":"2015","journal-title":"Best Pract Res Clin Endocrinol Metabol"},{"key":"2026070714152439600_bib12","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/BF02550500","article-title":"Gonadotropin therapy in males with hypogonadotropic hypogonadism: factors affecting induction of spermatogenesis after gonadotropin replacement","volume":"28","author":"Fuse","year":"1996","journal-title":"Int Urol Nephrol"},{"key":"2026070714152439600_bib13","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1111\/andr.13388","article-title":"Clomiphene citrate for male infertility: a systematic review and meta-analysis","volume":"11","author":"Huijben","year":"2023","journal-title":"Andrology"},{"key":"2026070714152439600_bib14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1365-2605.1994.tb01249.x","article-title":"Induction of spermatogenesis with gonadotrophins in Chinese men with hypogonadotrophic hypogonadism","volume":"17","author":"Kung","year":"1994","journal-title":"Int J Androl"},{"key":"2026070714152439600_bib15","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1210\/jcem-67-6-1140","article-title":"Two-year comparison of testicular responses to pulsatile gonadotropin-releasing hormone and exogenous gonadotropins from the inception of therapy in men with isolated hypogonadotropic hypogonadism","volume":"67","author":"Liu","year":"1988","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070714152439600_bib16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.avsg.2016.01.051","article-title":"Clinical effectiveness of endovascular therapy for total occlusion of the subclavian arteries: a study of 67 patients","volume":"35","author":"Liu","year":"2016","journal-title":"Ann Vasc Surg"},{"key":"2026070714152439600_bib17","first-page":"1","article-title":"Gonadotropin-induced spermatogenesis in CHH patients with cryptorchidism","volume":"2019","author":"Liu","year":"2019","journal-title":"Int J Endocrinol"},{"key":"2026070714152439600_bib18","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.eprac.2021.04.009","article-title":"Gonadotropin therapy once a week for spermatogenesis in hypogonadotropic hypogonadism","volume":"27","author":"Ma","year":"2021","journal-title":"Endocr Pract"},{"key":"2026070714152439600_bib19","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.fertnstert.2008.07.1742","article-title":"Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone in azoospermic men with hypogonadotropic hypogonadism","volume":"92","author":"Matsumoto","year":"2009","journal-title":"Fertil Steril"},{"key":"2026070714152439600_bib20","doi-asserted-by":"crossref","first-page":"623","DOI":"10.4103\/aja.aja_6_19","article-title":"Evaluation of gonadotropin-replacement therapy in male hypogonadotropic hypogonadism","volume":"21","author":"Ortac","year":"2019","journal-title":"Asian J Androl"},{"key":"2026070714152439600_bib21","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/cen.13850","article-title":"Fertility induction in hypogonadotropic hypogonadal men","volume":"89","author":"Prior","year":"2018","journal-title":"Clin Endocrinol"},{"key":"2026070714152439600_bib22","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1111\/andr.262","article-title":"Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study","volume":"2","author":"Rastrelli","year":"2014","journal-title":"Andrology"},{"key":"2026070714152439600_bib23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/andr.12128","article-title":"Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults","volume":"4","author":"Rohayem","year":"2016","journal-title":"Andrology"},{"key":"2026070714152439600_bib24","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S0015-0282(16)54730-X","article-title":"Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism","volume":"56","author":"Schopohl","year":"1991","journal-title":"Fertil Steril"},{"key":"2026070714152439600_bib25","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.eururo.2021.06.007","article-title":"European Association of Urology guidelines on sexual and reproductive health \u2013 2021 update: male sexual dysfunction","volume":"80","author":"Salonia","year":"2021","journal-title":"Eur Urol"},{"key":"2026070714152439600_bib26","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/j.1365-2605.1992.tb01131.x","article-title":"Therapy with human chorionic gonadotrophin alone induces spermatogenesis in men with isolated hypogonadotrophic hypogonadism","volume":"15","author":"Vicari","year":"1992","journal-title":"Int J Androl"},{"key":"2026070714152439600_bib27","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1177\/0391560319882231","article-title":"A review of hypogonadotropic hypogonadism cases followed up in our clinic in the last decade","volume":"88","author":"Y\u0131lmazel","year":"2021","journal-title":"Urologia J"},{"key":"2026070714152439600_bib28","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1210\/er.2018-00116","article-title":"Clinical management of congenital hypogonadotropic hypogonadism","volume":"40","author":"Young","year":"2019","journal-title":"Endocr Rev"},{"key":"2026070714152439600_bib29","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.fertnstert.2012.06.022","article-title":"Addition of recombinant follicle-stimulating hormone to human chorionic gonadotropin treatment in adolescents and young adults with hypogonadotropic hypogonadism","volume":"98","author":"Zacharin","year":"2012","journal-title":"Fertil Steril"},{"key":"2026070714152439600_bib30","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1210\/jc.2014-3802","article-title":"Sequential versus continual purified urinary FSH\/hCG in men with idiopathic hypogonadotropic hypogonadism","volume":"100","author":"Zhang","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"key":"2026070714152439600_bib31","doi-asserted-by":"crossref","DOI":"10.1177\/1557988318818280","article-title":"The pulsatile gonadorelin pump induces earlier spermatogenesis than cyclical gonadotropin therapy in congenital hypogonadotropic hypogonadism men","volume":"13","author":"Zhang","year":"2019","journal-title":"Am J Mens Health"},{"key":"2026070714152439600_bib32","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/j.1365-2605.2004.00519.x","article-title":"Intracytoplasmic sperm injection as a complement to gonadotrophin treatment in infertile men with hypogonadotrophic hypogonadism","volume":"28","author":"Zorn","year":"2005","journal-title":"Int J Androl"}],"container-title":["Reproduction and Fertility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/raf.bioscientifica.com\/view\/journals\/raf\/7\/2\/RAF-25-0100.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/raf.bioscientifica.com\/downloadpdf\/journals\/raf\/7\/2\/RAF-25-0100.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/raf\/article-pdf\/doi\/10.1530\/RAF-25-0100\/521426\/raf-25-0100.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/raf\/article-pdf\/doi\/10.1530\/RAF-25-0100\/521426\/raf-25-0100.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T18:16:47Z","timestamp":1783448207000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/raf\/article\/7\/2\/RAF250100\/77659\/Therapeutic-benefits-of-gonadotropins-in-male"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1530\/raf-25-0100","relation":{},"ISSN":["2633-8386"],"issn-type":[{"value":"2633-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]},"article-number":"RAF250100"}}