Predicting Biochemical Response to Clomiphene Citrate in Men with Hypogonadism
Abstract
Introduction Clomiphene citrate (CC) is as an effective treatment for men with hypogonadism (HG). Identifying the ideal candidate for this strategy has to date largely relied upon a patient's interest in preservation of testicular volume and spermatogenesis. Aim This analysis was undertaken to define if predictors existed of robust elevation in serum testosterone (T) levels in response to CC. Methods Seventy-six men with a diagnosis of HG (two separate early morning total T levels Main outcome measure Successful biochemical response to CC, defined as an increase of ≥200 ng/dL in total T level at ≥6 months after commencing CC, was the main outcome measure. Results Mean age was 46 ± 22 years. Mean pretreatment testicular volume was 16 ± 8 mL. Mean baseline T and LH levels were 179 ± 72 ng/dL and 7.2 ± 5.6 IU/mL, respectively. Mean total T on CC was 467 ± 190 ng/dL. Forty-seven patients (62%) met the responder definition, with a mean increase in total T levels of 302 ± 76 (204-464) ng/dL. In CC responders, the mean LH rise was 5.6 ± 3.1 IU/mL. On multivariable analysis, factors predictive of CC response included: mean testicular volume (adjusted [adj.] r = 0.32, P Conclusion These data indicate that two thirds of men with HG meet a robust responder definition and that pretreatment testicular volume and LH levels (in continuous and dichotomized fashions) are predictors of response.
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Testosterone deficient patients with low or low/normal LH levels are candidates for selective estrogen receptor modulator use as treatment, particularly those wishing to preserve fertility.
“Testosterone deficient patients with low or low/normal LH levels are also candidates for selective estrogen receptor modulator use as a treatment for testosterone deficiency, particularly those wishing to preserve their fertility.”
From Evaluation and Management of Testosterone Deficiency: AUA Guideline (2018) · cites this paper as [18]
Multiple studies have shown that clomiphene citrate effectively raises testosterone to eugonadal levels in men with testosterone deficiency.
“CC has long been used as a treatment to restore testosterone levels and promote or preserve spermatogenesis in men with testosterone deficiency desiring to preserve fertility, and multiple studies have shown that CC effectively raises testosterone to eugonadal levels (50-56).”
From Non-testosterone management of male hypogonadism: an examination of the existing literature (2020) · cites this paper as [52]
One retrospective study in 66 men identified pretreatment testicular volume ≥14 mL and mean LH level ≤6 IU/mL as predictors of good response to treatment with clomiphene citrate.
“One retrospective study in 66 men identified pretreatment testicular volume ≥14 mL and mean LH level ≤6 IU/mL as predictors of good response to treatment with clomiphene citrate [48].”
From Treatment of Men with Central Hypogonadism: Alternatives for Testosterone Replacement Therapy (2020) · cites this paper as [48]
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Prevalence of Symptomatic Androgen Deficiency in Men
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Outcomes of clomiphene citrate treatment in young hypogonadal men
Katz, D. J., Nabulsi, O., Tal, R., & Mulhall, J. P. (2012) · BJU International · doi:10.1111/j.1464-410x.2011.10702.x · Cited by 142 · see citing works
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Evaluation and Management of Testosterone Deficiency: AUA Guideline
Mulhall, J. P., Trost, L. W., Brannigan, R. E., Kurtz, E. G., Redmon, J. B., Chiles, K. A., Lightner, D. J., Miner, M. M., Murad, M. H., Nelson, C. J., et al. (2018) · Journal of Urology · doi:10.1016/j.juro.2018.03.115 · Cited by 766 · see citing works
Self-citationTreatment 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 · see citing works
Clomiphene Citrate for the Treatment of Hypogonadism
Wheeler, K. M., Sharma, D., Kavoussi, P. K., Smith, R. P., & Costabile, R. (2019) · Sexual Medicine Reviews · doi:10.1016/j.sxmr.2018.10.001 · Cited by 81 · see citing works
Non-testosterone management of male hypogonadism: an examination of the existing literature
Krzastek, S. C., & Smith, R. P. (2020) · Translational Andrology and Urology · doi:10.21037/tau.2019.11.16 · Cited by 34 · see citing works
“testosterone deficiency desiring to preserve fertility, and multiple studies have shown that CC effectively raises testosterone to eugonadal levels (50-56).”
BackgroundIs There Room for SERMs or SARMs as Alternative Therapies for Adult Male Hypogonadism?
Giagulli, V. A., Silvestrini, A., Bruno, C., Triggiani, V., Mordente, A., & Mancini, A. (2020) · International Journal of Endocrinology · doi:10.1155/2020/9649838 · Cited by 14 · see citing works
- Authors
- Mazzola, C. R., Katz, D. J., Loghmanieh, N., Nelson, C. J., & Mulhall, J. P.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Mulhall, John P.
- Venue
- The Journal of Sexual Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-09-01
- Volume
- 11
- Issue
- 9
- Pages
- 2302-2307
- ISSN
- 1743-6095 (ISSN-L)
- 1743-6109
- OpenAlex
- W1896835143
- Cited by
- 50
- References
- 5
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 2 · 2020: 6 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 8 · 2015: 2 · 2014: 1
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- The Journal of Sexual Medicine (publishedVersion)
- PubMed (publishedVersion)
- 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 › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- clomiphene citrate, male hypogonadism, testicular volume, luteinizing hormone, varicocele, spermatogenesis, predictors of treatment response, luteinizing hormone suppression, varicocelectomy
- MeSH terms
- Adult, Aged, Clomiphene, Humans, Hypogonadism, Male, Middle Aged, Retrospective Studies, Young Adult
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