{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:17Z","timestamp":1787028437624,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Central hypogonadism is a clinical condition, characterized by sexual symptoms and low serum testosterone levels, due to an impaired function of the hypothalamus or pituitary gland. Testosterone replacement therapy (TRT) is the standard treatment for hypogonadism, but it has some disadvantages. TRT is not a good option in men wishing to preserve fertility, nor in men with (a high risk of) prostate cancer, polycythemia, thrombophilia and severe cardiovascular disease. In this review, we discuss alternative treatments for central hypogonadism. If reversible causes are present, non-pharmacological interventions can be therapeutic. Gonadotropins are a good alternative to TRT when fertility is desired in the near future though they require frequent injections. Clomiphene citrate and tamoxifen seem to be a safe alternative for the treatment of functional central hypogonadism in men, as several studies reported a significant increase in testosterone levels with these drugs. However, their use is off-label and data supporting the efficacy of clomiphene citrate and tamoxifen on hypogonadal symptoms are insufficient. For this reason, clomiphene citrate and tamoxifen should not be used in routine clinical practice to treat sexual symptoms in men with central hypogonadism.<\/jats:p>","DOI":"10.3390\/ijms22010021","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T20:39:29Z","timestamp":1608669569000},"page":"21","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy"],"prefix":"10.3390","volume":"22","author":[{"given":"Veerle","family":"Ide","sequence":"first","affiliation":[{"name":"Department of Endocrinology, University Hospitals Leuven, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Vanderschueren","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospitals Leuven, B-3000 Leuven, Belgium"},{"name":"Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KULeuven, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1079-2860","authenticated-orcid":false,"given":"Leen","family":"Antonio","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, University Hospitals Leuven, B-3000 Leuven, Belgium"},{"name":"Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KULeuven, B-3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41572-019-0087-y","article-title":"Paediatric and adult-onset male hypogonadism","volume":"5","author":"Salonia","year":"2019","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Corona, G., Goulis, D.G., Huhtaniemi, I., Zitzmann, M., Toppari, J., Forti, G., Vanderschueren, D., Wu, F.C., Corona, G., and Goulis, D.G. (2020). European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males. Andrology, 12770.","DOI":"10.1111\/andr.12770"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1210\/jc.2018-00229","article-title":"Testosterone Therapy in Men with Hypogonadism: An Endocrine Society Clinical Practice Guideline","volume":"103","author":"Bhasin","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Awouters, M., Vanderschueren, D., and Antonio, L. (2019). Aromatase inhibitors and selective estrogen receptor modulators: Unconventional therapies for functional hypogonadism?. Andrology, 1\u20138.","DOI":"10.1111\/andr.12725"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrendo.2015.112","article-title":"Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism-pathogenesis, diagnosis and treatment","volume":"11","author":"Boehm","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1530\/EJE-17-0065","article-title":"Characteristics of a nationwide cohort of patients presenting with isolated hypogonadotropic hypogonadism (IHH)","volume":"178","author":"Bonomi","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cangiano, B., Swee, D.S., Quinton, R., and Bonomi, M. (2020). Genetics of congenital hypogonadotropic hypogonadism: Peculiarities and phenotype of an oligogenic disease. Qual. Life Res., 1\u201335.","DOI":"10.1007\/s00439-020-02147-1"},{"key":"ref_8","first-page":"183","article-title":"Hereditary Hemochromatosis","volume":"87","author":"Crownover","year":"2013","journal-title":"Am. Fam. Physician"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1210\/jc.2016-3580","article-title":"A Perspective on Middle-Aged and Older Men with Functional Hypogonadism: Focus on Holistic Management","volume":"102","author":"Grossmann","year":"2017","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"192","DOI":"10.4103\/1008-682X.122336","article-title":"Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment","volume":"16","author":"Huhtaniemi","year":"2014","journal-title":"Asian J. Androl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1056\/NEJMoa0911101","article-title":"Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men","volume":"363","author":"Wu","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1210\/jc.2007-1972","article-title":"Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European male aging study","volume":"93","author":"Wu","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1210\/jc.2015-1571","article-title":"Development of and Recovery from Secondary Hypogonadism in Aging Men: Prospective Results from the EMAS","volume":"100","author":"Rastrelli","year":"2015","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cangiano, B., Duminuco, P., Vezzoli, V., Guizzardi, F., Chiodini, I., Corona, G., Maggi, M., Persani, L., and Bonomi, M. (2019). Evidence for a Common Genetic Origin of Classic and Milder Adult-Onset Forms of Isolated Hypogonadotropic Hypogonadism. J. Clin. Med., 8.","DOI":"10.3390\/jcm8010126"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"781","DOI":"10.3389\/fendo.2019.00781","article-title":"A Rare SPRY4 Gene Mutation Is Associated with Anosmia and Adult-Onset Isolated Hypogonadotropic Hypogonadism","volume":"10","author":"Indirli","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1210\/er.2017-00234","article-title":"Lessons from the Testosterone Trials","volume":"39","author":"Snyder","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1016\/j.jsxm.2016.10.009","article-title":"Diagnosis and Treatment of Testosterone Deficiency: Recommendations from the Fourth International Consultation for Sexual Medicine (ICSM 2015)","volume":"13","author":"Khera","year":"2016","journal-title":"J. Sex. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1210\/jc.2006-1859","article-title":"The Relative Contributions of Aging, Health, and Lifestyle Factors to Serum Testosterone Decline in Men","volume":"92","author":"Travison","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"161","DOI":"10.7326\/0003-4819-139-3-200308050-00005","article-title":"Sexual Function in Men Older Than 50 Years of Age: Results from the Health Professionals Follow-up Study","volume":"139","author":"Bacon","year":"2003","journal-title":"Ann. Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1530\/EJE-12-0890","article-title":"Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: Longitudinal results from the European Male Ageing Study","volume":"168","author":"Camacho","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1530\/EJE-12-0955","article-title":"Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: A systematic review and meta-analysis","volume":"168","author":"Corona","year":"2013","journal-title":"Eur. J. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"726","DOI":"10.2164\/jandrol.108.007005","article-title":"Fifty-two-Week Treatment with Diet and Exercise Plus Transdermal Testosterone Reverses the Metabolic Syndrome and Improves Glycemic Control in Men with Newly Diagnosed Type 2 Diabetes and Subnormal Plasma Testosterone","volume":"30","author":"Heufelder","year":"2009","journal-title":"J. Androl."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mongio\u00ec, L.M., Cimino, L., Condorelli, R.A., Magagnini, M.C., Barbagallo, F., Cannarella, R., la Vignera, S., and Calogero, A.E. (2020). Effectiveness of a Very Low Calorie Ketogenic Diet on Testicular Function in Overweight\/Obese Men. Nutrients, 12.","DOI":"10.3390\/nu12102967"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"La Vignera, S., Cannarella, R., Galvano, F., Grillo, A., Aversa, A., Cimino, L., Magagnini, C.M., Mongio\u00ec, L.M., Condorelli, R.A., and Calogero, A.E. (2020). The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic \u00df-cell function in overweight\/obese men: A single-arm uncontrolled study. Endocrine, 1\u20138.","DOI":"10.1007\/s12020-020-02518-8"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1001\/jama.291.24.2978","article-title":"Effect of lifestyle changes on erectile dysfunction in obese men: A randomized controlled trial","volume":"291","author":"Esposito","year":"2004","journal-title":"J. Am. Med. Assoc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.esxm.2019.06.003","article-title":"Effect of Bariatric Surgery on Male Sexual Function: A Meta-Analysis and Systematic Review","volume":"7","author":"Xu","year":"2019","journal-title":"Sex. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.drugalcdep.2015.01.038","article-title":"Testosterone suppression in opioid users: A systematic review and meta-analysis","volume":"149","author":"Bawor","year":"2015","journal-title":"Drug Alcohol Depend."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1111\/j.1365-2265.2006.02461.x","article-title":"The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males","volume":"64","author":"Rosa","year":"2006","journal-title":"Clin. Endocrinol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1007\/BF03345775","article-title":"Epidemiology; diagnosis, and treatment of male hypogonadotropic hypogonadism","volume":"32","author":"Lenzi","year":"2009","journal-title":"J. Endocrinol. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1210\/jc.2003-030979","article-title":"Outcome of Cabergoline Treatment in Men with Prolactinoma: Effects of a 24-Month Treatment on Prolactin Levels, Tumor Mass, Recovery of Pituitary Function, and Semen Analysis","volume":"89","author":"Colao","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_31","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":"ref_32","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1056\/NEJM198509123131102","article-title":"Stimulation of Spermatogenesis by Gonadotropins in Men with Hypogonadotropic Hypogonadism","volume":"313","author":"Finkel","year":"1985","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12958-017-0232-y","article-title":"An open-label clinical trial to investigate the efficacy and safety of corifollitropin alfa combined with hCG in adult men with hypogonadotropic hypogonadism","volume":"15","author":"Nieschlag","year":"2017","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1007\/BF03346659","article-title":"Efficacy of recombinant human follicle stimulating hormone at low doses in inducing spermatogenesis and fertility in hypogonadotropic hypogonadism","volume":"33","author":"Sinisi","year":"2010","journal-title":"J. Endocrinol. Investig."},{"key":"ref_35","first-page":"121","article-title":"Clinical Applications of Gonadotropins in the Male","volume":"143","year":"2016","journal-title":"Prog. Mol. Biol. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/cen.13164","article-title":"Testicular growth and spermatogenesis: New goals for pubertal hormone replacement in boys with hypogonadotropic hypogonadism? A multicentre prospective study of hCG\/rFSH treatment outcomes during adolescence","volume":"86","author":"Rohayem","year":"2017","journal-title":"Clin. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"68","DOI":"10.12688\/f1000research.10102.1","article-title":"Treatment of hypogonadism: Current and future therapies","volume":"6","author":"Thirumalai","year":"2017","journal-title":"F1000Research"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"32","DOI":"10.4103\/2230-8210.119500","article-title":"Endocrine management of male subfertility","volume":"17","author":"George","year":"2013","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E1790","DOI":"10.1210\/jc.2013-2518","article-title":"Trial of Recombinant Follicle-Stimulating Hormone Pretreatment for GnRH-Induced Fertility in Patients with Congenital Hypogonadotropic Hypogonadism","volume":"98","author":"Dwyer","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_40","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. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1210\/jcem-66-6-1144","article-title":"Gonadotropin therapy in men with isolated hypogonadotropic hypogonadism: The response to human chorionic gonadotropin is predicted by initial testicular size","volume":"66","author":"Burris","year":"1988","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","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-long-term follow-up","volume":"15","author":"Vicari","year":"1992","journal-title":"Int. J. Androl."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s11255-011-0065-0","article-title":"Application of hormonal treatment in hypogonadotropic hypogonadism: More than ten years experience","volume":"44","author":"Yang","year":"2012","journal-title":"Int. Urol. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/j.fertnstert.2008.07.1720","article-title":"A combined analysis of data to identify predictive factors for spermatogenesis in men with hypogonadotropic hypogonadism treated with recombinant human follicle-stimulating hormone and human chorionic gonadotropin","volume":"92","author":"Warne","year":"2009","journal-title":"Fertil. Steril."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1210\/jcem.87.7.8630","article-title":"A Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Recombinant Human Chorionic Gonadotropin on Muscle Strength and Physical Function and Activity in Older Men with Partial Age-Related Androgen Deficiency","volume":"87","author":"Liu","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11934-018-0816-x","article-title":"Novel Therapy for Male Hypogonadism","volume":"19","author":"Carrasquillo","year":"2018","journal-title":"Curr. Urol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Giagulli, V.A., Silvestrini, A., Bruno, C., Triggiani, V., Mordente, A., and Mancini, A. (2020). Is There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?. Int. J. Endocrinol., 2020.","DOI":"10.1155\/2020\/9649838"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1111\/jsm.12592","article-title":"Predicting Biochemical Response to Clomiphene Citrate in Men with Hypogonadism","volume":"11","author":"Mazzola","year":"2014","journal-title":"J. Sex. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Cangiano, B., Cacciatore, C., Persani, L., and Bonomi, M. (2017). Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis. Endocrinol. Diabetes Metab. Case Rep., 2017.","DOI":"10.1530\/EDM-17-0055"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.juro.2016.10.068","article-title":"A Comparison of Secondary Polycythemia in Hypogonadal Men Treated with Clomiphene Citrate versus Testosterone Replacement: A Multi-Institutional Study","volume":"197","author":"Wheeler","year":"2017","journal-title":"J. Urol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1111\/j.2047-2927.2013.00107.x","article-title":"Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: A meta-analysis","volume":"1","author":"Chua","year":"2013","journal-title":"Andrology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/j.1743-6109.2005.00075.x","article-title":"Clomiphene citrate effects on testosterone\/estrogen ratio in male hypogonadism","volume":"2","author":"Shabsigh","year":"2005","journal-title":"J. Sex. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1743-6109.2009.01454.x","article-title":"Clomiphene Citrate and Testosterone Gel Replacement Therapy for Male Hypogonadism: Efficacy and Treatment Cost","volume":"7","author":"Taylor","year":"2010","journal-title":"J. Sex. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1111\/j.1464-410X.2011.10702.x","article-title":"Outcomes of clomiphene citrate treatment in young hypogonadal men","volume":"110","author":"Katz","year":"2012","journal-title":"BJU Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/bju.13337","article-title":"Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: Restoration instead of replacement","volume":"117","author":"Kim","year":"2016","journal-title":"BJU Int."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pelusi, C., Giagulli, V.A., Baccini, M., Fanelli, F., Mezzullo, M., Fazzini, A., Bianchi, N., Carbone, M.D., de Pergola, G., and Mastroroberto, M. (2017). Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: A randomized, double-blind, placebo-controlled study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183369"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.sxmr.2018.10.001","article-title":"Clomiphene Citrate for the Treatment of Hypogonadism","volume":"7","author":"Wheeler","year":"2019","journal-title":"Sex. Med. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"(1992). A double-blind trial of clomiphene citrate for the treatment of idiopathic male infertility. Int. J. Androl., 15, 299\u2013307.","DOI":"10.1111\/j.1365-2605.1992.tb01129.x"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1111\/jsm.12116","article-title":"Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: Comparison with testosterone gel","volume":"10","author":"Kaminetsky","year":"2013","journal-title":"J. Sex. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1080\/14656566.2019.1615057","article-title":"Effects of the selective estrogen receptor modulators for the treatment of male infertility: A systematic review and meta-analysis","volume":"20","author":"Cannarella","year":"2019","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.juro.2014.03.089","article-title":"Testosterone Supplementation Versus Clomiphene Citrate for Hypogonadism: An Age Matched Comparison of Satisfaction and Efficacy","volume":"192","author":"Ramasamy","year":"2014","journal-title":"J. Urol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/s41366-018-0105-2","article-title":"Effects of clomiphene citrate on male obesity-associated hypogonadism: A randomized, double-blind, placebo-controlled study","volume":"42","author":"Soares","year":"2018","journal-title":"Int. J. Obes."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1097\/JU.0000000000000396","article-title":"Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism","volume":"202","author":"Krzastek","year":"2019","journal-title":"J. Urol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1111\/j.1464-410X.2012.10968.x","article-title":"Clomiphene citrate is safe and effective for long-term management of hypogonadism","volume":"110","author":"Moskovic","year":"2012","journal-title":"BJU Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1111\/andr.12197","article-title":"Tamoxifen in men: A review of adverse events","volume":"4","author":"Wibowo","year":"2016","journal-title":"Andrology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1111\/jsm.12944","article-title":"A Randomized Prospective Double-Blind Comparison Trial of Clomiphene Citrate and Anastrozole in Raising Testosterone in Hypogonadal Infertile Men","volume":"12","author":"Helo","year":"2015","journal-title":"J. Sex. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1365-2265.2008.03327.x","article-title":"Effects of aromatase inhibition in hypogonadal older men: A randomized, double-blind, placebo-controlled trial","volume":"70","author":"Roupenian","year":"2009","journal-title":"Clin. Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/andr.12126","article-title":"Effects of aromatase inhibition vs. testosterone in older men with low testosterone: Randomized-controlled trial","volume":"4","author":"Dias","year":"2016","journal-title":"Andrology"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/1\/21\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:48:21Z","timestamp":1760179701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/1\/21"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,22]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ijms22010021"],"URL":"https:\/\/doi.org\/10.3390\/ijms22010021","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,22]]}}}