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AROMATASE INHIBITORS FOR MALE INFERTILITY
Abstract
PURPOSE: Testosterone-to-estradiol ratio levels in infertile men improve during treatment with the aromatase inhibitor, testolactone, and resulting changes in semen parameters. We evaluated the effect of anastrozole, a more selective aromatase inhibitor, on the hormonal and semen profiles of infertile men with abnormal baseline testosterone-to-estradiol ratios. MATERIALS AND METHODS: A total of 140 subfertile men with abnormal testosterone-to-estradiol ratios were treated with 100 to 200 mg. testolactone daily or 1 mg. anastrozole daily. Changes in testosterone, estradiol, testosterone-to-estradiol ratios and semen parameters were evaluated during therapy. The effect of obesity, diagnosis of the Klinefelter syndrome, and presence of varicocele and/or history of varicocele repair on treatment results was studied. RESULTS: Men treated with testolactone had an increase in testosterone-to-estradiol ratios during therapy (mean plus or minus standard error of the mean 5.3 +/- 0.2 versus 12.4 +/- 1.1, p <0.001). This change was confirmed in subgroups of men with the Klinefelter syndrome, a history of varicocele repair and those with varicocele. A total of 12 oligospermic men had semen analysis before and during testolactone treatment with an increase in sperm concentration (5.5 versus 11.2 million sperm per ml., p <0.01), motility (14.7% versus 21.0%, p <0.05), morphology (6.5% versus 12.8%, p = 0.05), and motility index (606.3 versus 1685.2 million motile sperm per ejaculate, respectively, p <0.05) appreciated. During anastrozole treatment, similar changes in the testosterone-to-estradiol ratios were seen (7.2 +/- 0.3 versus 18.1 +/- 1.0, respectively, p <0.001). This improvement of hormonal parameters was noted for all subgroups except those patients with the Klinefelter syndrome. A total of 25 oligospermic men with semen analysis before and during anastrozole treatment had an increase in semen volume (2.9 versus 3.5 ml., p <0.05), sperm concentration (5.5 versus 15.6 million sperm per ml., p <0.001) and motility index (832.8 versus 2930.8 million motile sperm per ejaculate, respectively, p <0.005). These changes were similar to those observed in men treated with testolactone. No significant difference in serum testosterone levels during treatment with testolactone and anastrozole was observed. However, the anastrozole treatment group did have a statistically better improvement of serum estradiol concentration and testosterone-to-estradiol ratios (p <0.001). CONCLUSIONS: Men who are infertile with a low serum testosterone-to-estradiol ratio can be treated with an aromatase inhibitor. With treatment, an increase in testosterone-to-estradiol ratio occurred in association with increased semen parameters. Anastrozole and testolactone have similar effects on hormonal profiles and semen analysis. Anastrazole appears to be at least as effective as testolactone for treating men with abnormal testosterone-to-estradiol ratios, except for the subset with the Klinefelter syndrome, who appeared to be more effectively treated with testolactone.
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“For this reason, alternative therapies, including select estrogen receptor modulators, 47 human chorionic gonadotropin, 48 and aromatase inhibitors 49 are commonly used to promote the endogenous production of testosterone.”
From Evaluation and Management of Testosterone Deficiency: AUA Guideline (2018) · cites this paper as [49]
In the citing paper
“In three small studies, letrozole or testolactone has been administered to morbidly obese men to improve their testosterone levels [42-44].”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [42]
In the citing paper
“Treatment resulted in normalization of testosterone levels in all subjects, with a concomitant suppression of the originally increased levels of estradiol.”
From Aromatase inhibitors in men: effects and therapeutic options (2011) · cites this paper as [42]
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Self-citationRaman, J. D., & Schlegel, P. N. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(03)01927-7 · Cited by 1
Self-citationTreatment of Hypogonadism in Men
Mehta, A., Paduch, D. A., & Goldstein, M. (2012) · Springer eBooks · doi:10.1007/978-1-4471-4405-2_5 · Cited by 1
Medication Strategies for the Male with Unexplained Infertility
Starks, C. L., & Sabanegh, E. S. (2015) · Springer eBooks · doi:10.1007/978-1-4939-2140-9_24 · Cited by 1
Adjunct Management of Male Hypogonadism
Bach, P. V., Najari, B. B., & Kashanian, J. A. (2016) · Current Sexual Health Reports · doi:10.1007/s11930-016-0089-7 · Cited by 1
Management of Infertility in Klinefelter Syndrome
Ramasamy, R., & Zafar, A. (2016) · Springer eBooks · doi:10.1007/978-81-322-3604-7_8 · Cited by 1
The Complex Relationship Between Erectile Dysfunction and Hypogonadism in Diabetes Mellitus
Holland, L. C., Beilan, J. A., Tatem, A. J., & Lipshultz, L. I. (2019) · Current Sexual Health Reports · doi:10.1007/s11930-019-00216-9 · Cited by 1
Male Sexual and Reproductive Health
Tharakan, T., Minhas, S., & Jayasena, C. N. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00036-0 · Cited by 1
Association of Genetic and Reproductive Hormone with Infertility in Male
Khatoon, F. (2022) · Progress in Medical Sciences · doi:10.47363/pms/2022(6)175 · Cited by 1
Metadata
- Authors
- Raman, J. D., & Schlegel, P. N.
- Affiliations
- NewYork–Presbyterian Hospital (US)
- Venue
- Journal of Urology
- Published
- 2002-02
- Volume
- 167
- Issue
- 2 Part 1
- Pages
- 624-629
- ISSN
- 0022-5347 (ISSN-L)
- 1527-3792
- OpenAlex
- W2081837288
- Cited by
- 383
- References
- 13
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 16 · 2023: 13 · 2022: 14 · 2021: 19 · 2020: 19 · 2019: 13 · 2018: 14 · 2017: 24 · 2016: 17 · 2015: 19 · 2014: 17 · 2013: 32 · 2012: 20
- FWCI
- 12.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Urology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- male infertility, aromatase inhibitors, anastrozole, testolactone, testosterone/estradiol ratio, oligozoospermia, semen parameters, Klinefelter syndrome, varicocele, obesity, sperm motility, sperm morphology, sperm concentration, androgen therapy, estradiol, gonadotropins, GnRH agonist
- MeSH terms
- Anastrozole, Enzyme Inhibitors, Estradiol, Humans, Infertility, Male, Klinefelter Syndrome, Liver Function Tests, Male, Nitriles, Sperm Motility, Testolactone, Testosterone, Triazoles, Aromatase Inhibitors
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