Spontaneous fertility in a male patient with testotoxicosis despite suppression of FSH levels
Abstract
Testotoxicosis is a rare cause of peripheral precocious puberty in boys caused by constitutively activating mutations of the LHCG receptor. Affected males usually have normal gonadotropin profiles and fertility in their adult life. Here, we described the long-term follow-up of a 24-year-old young man with severe testotoxicosis due to a de novo activating mutation in the third transmembrane helix of the LHCGR (p.Leu457Arg). This patient was treated with different medications, including medroxyprogesterone acetate, ketoconazole, cyproterone acetate and aromatase inhibitor from age 2.5 to 9.5 years. His basal and GnRH-stimulated gonadotropin levels were continually suppressed during and after medical treatment. At adulthood, extremely high serum testosterone levels (>35 nmol/L), undetectable gonadotropin levels (LH < 0.15 IU/L and FSH < 0.6 IU/L) and oligozoospermia were evidenced. Despite his suppressed FSH levels and an unfavorable spermogram, the patient fathered a healthy girl and biological paternity was confirmed through analysis of microsatellites. Spontaneous fertility in a young man with severe testotoxicosis and chronic suppression of FSH levels reinforces the key role of high intratesticular testosterone levels in human spermatogenesis.
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Confirmatory evidence in humans from rare cases of men with an activating mutation of the chorionic gonadotropin/LH receptor shows that high testosterone without gonadotropin stimulation induced sperm production and allowed natural paternity.
“Nevertheless, confirmatory evidence in humans is available from rare cases of men with an activating mutation of the chorionic gonadotropin/LH receptor (73, 74).”
From Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance (2018) · cites this paper as [74]
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Circulating Testosterone as the Hormonal Basis of Sex Differences in Athletic Performance
Handelsman, D. J., Hirschberg, A. L., & Bermon, S. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00020 · Cited by 594 · see citing works
- Authors
- Cunha-Silva, M., Brito, V. N., Macedo, D. B., Bessa, D. S., Ramos, C. O., Lima, L. G., Barroso, P. S., Arnhold, I. J. P., Segaloff, D. L., Mendonca, B. B., & Latronico, A. C.
- Affiliations
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
- Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM/42, Disciplina de Endocrinologia e Metabologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil
- University of Iowa (US)
- Corresponding author
- Latronico, A C
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-03-12
- Volume
- 33
- Issue
- 5
- Pages
- 914-918
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2791102922
- Cited by
- 6
- References
- 31
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 1 · 2021: 1 · 2018: 1
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (403525/2016, 302849/2015-7)
- Fundação de Amparo à Pesquisa do Estado de São Paulo (13/03236-5)
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- testotoxicosis, LHCGR, activating mutations, peripheral precocious puberty, oligozoospermia, FSH suppression, gonadotropin suppression, intratesticular testosterone, spermatogenesis, medroxyprogesterone acetate, ketoconazole, cyproterone acetate, aromatase inhibitors
- MeSH terms
- Adult, Fertility, Humans, Male, Mutation, Puberty, Precocious, Receptors, LH, Testosterone
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