The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Switch to restoration therapy in a testosterone treated central hypogonadism with erythrocytosis
Open accessAbstract
We describe a case of severe erythrocytosis caused by testosterone replacement therapy in a 66-year-old man affected with hypogonadotropic hypogonadism (HH) determining osteoporosis, resolved by switching to restoration therapy with clomiphene citrate. The patient complained fatigue, loss of libido and defective erections and a spontaneous vertebral fracture despite bisphosphonate therapy and vitamin D supplementation. The examinations proved isolated HH and he was therefore treated with testosterone gel with regression of specific manifestations but elevated hemoglobin and hematocrit values. Therefore, it was decided to switch to a restoration therapy with clomiphene citrate 25 mg/die, which resulted in the resolution of symptoms without evident side effects. In a couple of months, the patient showed normalization of testosterone levels and increment of testicular volume. Since secondary hypogonadism is the consequence of an insufficient stimulation of the gonads by hypothalamic-pituitary axis, therapeutic approaches aimed to restore endogenous testosterone production should be considered in alternative to testosterone replacement, particularly if side effects intervene. Among these strategies, clomiphene citrate seems to have a high efficacy and safety profile also in the elderly with isolated HH and no evident pituitary lesion. LEARNING POINTS: Hypogonadism should always be assessed in patients with severe loss in BMD and undergo appropriate medical treatment.In hypogonadotropic hypogonadism, more approaches are available other than testosterone replacement therapy alone.In patients with severe late-onset central hypogonadism presenting with erythrocytosis even at low doses of replacement therapy, restoration therapy with clomiphene could prove to be an effective solution, particularly in patients with a reversible disruption of GNRH/gonadotropin functions.Clomiphene citrate increases gonadotropin levels and testicular volume and should therefore be considered in hypogonadal men who wish to remain fertile.
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Advantages of SERMs over TRT include oral administration, maintenance of fertility, avoidance of supraphysiological total testosterone levels, and lower risk of erythrocytosis.
“The advantages of these SERMs over TRT include oral administration, the maintenance of fertility, the avoidance of supraphysiological total testosterone levels and the lower risk of erythrocytosis [4,49,50].”
From Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy (2020) · cites this paper as [49]
The Discussion says clomiphene citrate (a SERM) is less likely to produce supraphysiological testosterone peaks and may benefit hypogonadal men who wish to remain fertile. The Treatment and Outcome sections document erythrocytosis on TRT that resolved after switching to clomiphene, but this single case does not establish a generally lower risk for SERMs; the copy also does not state oral administration, and 'avoidance' is stronger than 'less likely.' (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe prevalence of secondary polycythemia is significantly lower during treatment with clomiphene citrate compared to TRT.
“The prevalence of secondary polycythemia is significantly lower during treatment with clomiphene citrate compared to TRT [49,50].”
From Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy (2020) · cites this paper as [49]
The Treatment and Outcome and follow-up sections report erythrocytosis during testosterone therapy in one patient and normal hematocrit after switching to clomiphene citrate (pages not provided). This supports the direction of the comparison for that patient, but a single case cannot establish a significantly lower prevalence of secondary polycythemia across treatments. (LLM, conf=0.87)
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Risks of testosterone-replacement therapy and recommendations for monitoring.
Rhoden, E. L., & Morgentaler, A. (2004) · New England Journal of Medicine · doi:10.1056/nejmra022251 · Cited by 705
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Research works printed but not linked: 10
- Vezzoli, 2016, The complex genetic basis of congenital hypogonadotropic hypogonadism, Minerva Endocrinologica, 41, 223
- Tajar, 2010, Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study, Journal of Clinical Endocrinology and Metabolism, 95, 1810, 10.1210/jc.2009-1796 · DOI · Paper page
- Samplaski, 2014, Testosterone use in the male infertility population: prescribing patterns and effects on semen and hormonal parameters, Fertility and Sterility, 101, 64, 10.1016/j.fertnstert.2013.09.003 · DOI
- Borst, 2007, Testosterone replacement therapy for older men, Clinical Interventions in Aging, 2, 561, 10.2147/CIA.S1609 · DOI
- Bachman, 2014, Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point, Journals of Gerontology: Series A, Biological Sciences and Medical Sciences, 69, 725, 10.1093/gerona/glt154 · DOI · Paper page
- McCullough, 2015, Alternatives to testosterone replacement: testosterone restoration, Asian Journal of Andrology, 17, 201, 10.4103/1008-682X.143736 · DOI
- Corona, 2012, Emerging medication for the treatment of male hypogonadism, Expert Opinion on Emerging Drugs, 17, 239, 10.1517/14728214.2012.683411 · DOI · Paper page
- Moskovic, 2012, Clomiphene citrate is safe and effective for long-term management of hypogonadism, BJU International, 110, 1524, 10.1111/j.1464-410X.2012.10968.x · DOI · Paper page
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Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy
Ide, V., Vanderschueren, D., & Antonio, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010021 · Cited by 101
Metadata
- Authors
- Cangiano, B., Cacciatore, C., Persani, L., & Bonomi, M.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Bonomi, M
- Venue
- Endocrinology, Diabetes & Metabolism Case Reports
- Publisher
- Bioscientifica
- Published
- 2017-07-07
- Volume
- 2017
- ISSN
- 2052-0573 (ISSN-L)
- PMC
- PMC5510393
- OpenAlex
- W2727314260
- Cited by
- 8
- References
- 1
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 3 · 2020: 1 · 2019: 1 · 2018: 1
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Endocrinology Diabetes and Metabolism Case Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Istituto Auxologico Italiano
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- hypogonadotropic hypogonadism, testosterone replacement therapy, erythrocytosis, clomiphene citrate, secondary hypogonadism, osteoporosis, vertebral fractures, bisphosphonate therapy, testosterone gel, testicular volume, gonadotropins, fertility preservation, older men
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