Androgen replacement therapy in Turner syndrome: a pilot study
Abstract
CONTEXT: Women with Turner syndrome (TS) have reduced levels of androgens due to ovarian failure. HYPOTHESES: Morbidity associated with TS, such as bone fragility, metabolic changes, obesity, neurocognitive profile, and sexual problems may partly relate to androgen insufficiency and improve on androgen replacement therapy (ART). OBJECTIVES: The objective of the study was to determine the effect of androgens on morbidity in TS. DESIGN: Fourteen TS women (aged 17-27 yr) participated in a randomized, double-blind, placebo-controlled crossover pilot. The study was conducted in a hospital outpatient clinic between December 2001 and July 2004. INTERVENTION: TS patients were on estrogen/progestin replacement therapy. Subjects received oral 1.5 mg methyl testosterone (ART) or placebo for 1 yr and the alternative for another year. MAIN OUTCOME MEASURES: The study compared body composition as a primary outcome, and physiology, biochemistry, visceral fat, cognition, and quality of life (QOL) as secondary outcomes. RESULTS: ART as compared with placebo reduced total cholesterol, triglycerides, and high-density lipoprotein cholesterol. It improved bone mineral density, increased lean body mass, and decreased fat mass. ART improved attention, reaction time, and verbal memory and had no effect on executive functions and spatial cognition. Patients reported improved QOL, including general health, coping with stress, and sexual desire. CONCLUSIONS: Androgen insufficiency plays a role in TS-impaired body composition, neurocognition, and QOL, and these aspects improve with ART, which was safe and effective when given for 1 yr.
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In one pilot study, androgen replacement therapy compared with placebo reduced total cholesterol, triglycerides, and HDL cholesterol in adolescents/young women with TS.
“One pilot study by Zuckerman-Levin et al. has looked at testosterone replacement in adolescents/young women with TS and confirmed that androgen replacement therapy (ART), as compared with placebo, reduced total cholesterol, triglycerides, but also HDL cholesterol.”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [381]
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“Recognizing the limitation in testosterone assays in women (16, 28), TS subjects of this study had low normal serum total testosterone, and its level increased on ART but remained in the normal range for women.”
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Puberty in the Female and Its Disorders
Rosenfield, R. L., Cooke, D. W., & Radovick, S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-62520-3.00016-6 · Cited by 22 · see citing works
New insights into the diagnosis and management of bone health in premature ovarian insufficiency
Nguyen, H. H., Milat, F., & Vincent, A. J. (2021) · Climacteric · doi:10.1080/13697137.2021.1917539 · Cited by 20 · see citing works
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Endocrine diseases, perspectives and care in Turner syndrome
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Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome
Gawlik, A., Hankus, M., Such, K., Drosdzol-Cop, A. B., Madej, P., Borkowska, M., Zachurzok, A., & Małecka‐Tendera, E. (2016) · Journal of Pediatric and Adolescent Gynecology · doi:10.1016/j.jpag.2016.03.005 · Cited by 14 · see citing works
Androgens in premenopausal women and women with premature ovarian insufficiency
Davis, S. R. (2021) · Climacteric · doi:10.1080/13697137.2020.1866530 · Cited by 13 · see citing works
Body image and sexual interests in adolescents and young adults with Prader–Willi syndrome
Gross‐Tsur, V., Eldar‐Geva, T., Benarroch, F., Rubinstein, O., & Hirsch, H. J. (2011) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.2011.201 · Cited by 12 · see citing works
Face perception in women with Turner syndrome and its underlying factors
Anaki, D., Zadikov-Mor, T., Gepstein, V., & Hochberg, Z. (2016) · Neuropsychologia · doi:10.1016/j.neuropsychologia.2016.08.024 · Cited by 12 · see citing works
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Distinct waves of ovarian follicles contribute to mouse oocyte production
Yin, Q., & Spradling, A. C. (2025) · eLife · doi:10.1101/2024.05.30.596686 · Cited by 10 · see citing works
Attard, C. C., Cameron‐Pimblett, A., Puri, D., Rosa, C. L., Talaulikar, V. S., Davies, M. C., Learner, H. I., Liao, L., & Conway, G. S. (2020) · Clinical Endocrinology · doi:10.1111/cen.14271 · Cited by 10 · see citing works
Musculoskeletal Health in Premature Ovarian Insufficiency. Part One: Muscle
Samad, N., Nguyen, H. H., Scott, D. S., Ebeling, P. R., & Milat, F. (2020) · Seminars in Reproductive Medicine · doi:10.1055/s-0040-1721797 · Cited by 10 · see citing works
A current perspective into young female sex hormone replacement: a review
Giordano Imbroll, M., & Gruppetta, M. (2020) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2020.1816820 · Cited by 7 · see citing works
Normal Performance in Non-Visual Social Cognition Tasks in Women with Turner Syndrome
Anaki, D., Zadikov-Mor, T., Gepstein, V., & Hochberg, Z. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00171 · Cited by 6 · see citing works
Androgen replacement therapy in women
Lebbe, M., Hughes, D., Reisch, N., & Arlt, W. (2012) · Expert Review of Endocrinology & Metabolism · doi:10.1586/eem.12.45 · Cited by 5 · see citing works
Distinct waves of ovarian follicles contribute to mouse oocyte productionPreprint
Yin, Q., & Spradling, A. C. (2025) · eLife · doi:10.7554/elife.107352 · Cited by 6 · see citing works
Use of androgens at different stages of life: reproductive period
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A danazolkezelés hatása C1-inhibitor-hiány okozta hereditaer angiooedemás gyermekek növekedésére
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Samad, N., Nguyen, H. H., Aleksova, J., Pasco, J. A., Kotowicz, M. A., Ebeling, P. R., Vincent, A. J., Zebaze, R. M. D., & Milat, F. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad158 · Cited by 2 · see citing works
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Davis, S. R. (2012) · Cambridge University Press eBooks · doi:10.1017/cbo9781139003353.024 · Cited by 2 · see citing works
Distinct waves of ovarian follicles contribute to mouse oocyte productionPreprint
Yin, Q., & Spradling, A. C. (2025) · eLife · doi:10.7554/elife.107352.1 · Cited by 1 · see citing works
Guimarães, M. M., Collett‐Solberg, P. F., Gallicchio, C. T., Coelho, C. D. S., Siqueira, R. D. A., & Alves, T. D. F. (2011) · Cited by 1 · see citing works
Does having Turner syndrome affect quality of life in Brazilian women compared to common population?
Estevez, M. B., Monteagudo, P. T., Oliveira, K. C., & Verreschi, I. T. N. (2019) · Archives of Endocrinology and Metabolism · doi:10.20945/2359-3997000000136 · Cited by 1 · see citing works
Infertilidad femenina de origen endocrino
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Infertilités féminines d’origine endocrinienne
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Hormone Replacement Therapy in Premature Ovarian Insufficiency
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Endocrine and Metabolic Consequences of Turner Syndrome
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Final Height Outcome in Girls with Turner Syndrome Treated with Growth Hormone and Low Dose Estrogen
Fathalla, O., Alghazir, N., Hadid, I., Ghawil, M., Mattar, S., Abdulgader, M., Doggah, M., & Abusrewil, S. (2022) · Khalij-Libya Journal of Dental and Medical Research · doi:10.47705/kjdmr.216109
Comparação de qualidade de vida e controle laboratorial em pessoas com e sem Síndrome de Turner
Estevez, M. B., Monteagudo, P. T., & Verreschi, I. T. N. (2023) · doi:10.22533/at.ed.467231412
Turner Syndrome and Gender Incongruence: Considerations for Gender Affirming Hormonal Therapy
Urban, V., & Krishna, K. B. (2025) · Case Reports in Endocrinology · doi:10.1155/crie/6687002
New genomic understanding and challenges in clinical care of Turner syndrome
Gravholt, C. H., Balle, C. M., Johannsen, E. B., Valsted, L. B., Hartogsohn, E. A. R., Bedei, I. A., Just, J., Backeljauw, P. F., & Stochholm, K. (2026) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(26)00192-0
Gonadal Hormones, Diseases, and Emerging Therapeutics
Mirza, F., Zakko, L., & Taxel, P. (2012) · Springer eBooks · doi:10.1007/978-1-4471-2745-1_3
- Authors
- Zuckerman-Levin, N., Frolova-Bishara, T., Militianu, D., Levin, M., Aharon-Peretz, J., & Hochberg, Z.
- Affiliations
- Division of Pediatric Endocrinology (N.Z.-L., M.L., Z.H.), Technion-Israel Institute of Technology, Haifa 31096, Israel
- Technion – Israel Institute of Technology (IL)
- Meyer Children’s Hospital, Rambam Medical Center, Insitute of Cognitive Neurology (T.F.-B., J.A.-P.), Technion-Israel Institute of Technology, Haifa 31096, Israel
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-12-01
- Volume
- 94
- Issue
- 12
- Pages
- 4820-4827
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2070564732
- Cited by
- 69
- References
- 58
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 1 · 2014: 3 · 2013: 5 · 2012: 8
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- Turner syndrome, testosterone replacement therapy, androgen deficiency, methyltestosterone, body composition, bone mineral density, lipid profile, neurocognitive function, quality of life, ovarian failure, estrogen-progestin therapy, visceral fat
- MeSH terms
- Adolescent, Adult, Androgens, Anthropometry, Body Composition, Double-Blind Method, Female, Humans, Lipids, Methyltestosterone, Neuropsychological Tests, Pilot Projects, Quality of Life, Turner Syndrome, Treatment Outcome, Cross-Over Studies, Sexuality, Hormone Replacement Therapy, Testosterone Congeners, Young Adult
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