The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
High Prevalence of Reduced Fecundity in Men with Congenital Adrenal Hyperplasia
Abstract
Context: Testicular adrenal rest tumors (TARTs) are regarded to contribute to the high prevalence of subfertility in males with congenital adrenal hyperplasia (CAH). Objectives: Our objectives were to evaluate reduced fecundity and its possible causes in well-controlled adult males with CAH, and to investigate diagnostic tools for improved treatment monitoring with respect to fertility outcomes. Design: In a cross-sectional study at the Department of Endocrinology at the University Hospital München, Germany, 22 adult male CAH patients (15 salt wasting and seven simple virilizing, age 19–48 yr) were clinically assessed according to their hormonal control. We performed testicular ultrasound (22 of 22), magnetic resonance imaging (18 of 22), and a semen analysis (19 of 22) in the participants. Results: All patients had a pathological semen analysis. TART prevalence was 10 of 22 (eight salt wasting, two simple virilizing). Poor therapy control was present in five patients, and all five had TARTs. Of the other 17 well-controlled patients with normal or suppressed adrenal androgens and 17-hydroxyprogesterone levels, five presented with TARTs. There was a significant correlation between sperm concentration and functional testicular volume (r = 0.70; P = 0.002), TART volume (r = −0.70; P = 0.036), as well as inhibin B levels (r = 0.75; P < 0.0001), respectively. In several men, hormonal control parameters suggested hypogonadism, with glucocorticoid overtreatment as a relevant factor for poor semen quality. Conclusions: Poor semen parameters are common in male CAH patients. TARTs, most likely reflecting undertreatment, as well as inhibin B are important indicators of fecundity. On the other hand, long-term glucocorticoid overtreatment also seems to contribute to low semen quality.
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In the citing paper
“In the virilizing forms of CAH, excess adrenal sex steroids can lead to hypogonadotropic hypogonadism 106,107 and increased progesterone can interfere with endometrial implantation.108,109”
From Congenital adrenal hyperplasia (2017) · cites this paper as [106]
In the citing paper
“Low inhibin B levels reflect declining Sertoli cell function and can be used to monitor.106”
From Congenital adrenal hyperplasia (2017) · cites this paper as [106]
In the citing paper
“Fertility in males with CAH is often impaired (226, 237, 248-250).”
From Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society* Clinical Practice Guideline (2018) · cites this paper as [248]
In the citing paper
“TARTs have no malignant features but can lead to obstructive azoospermia and infertility (248).”
From Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society* Clinical Practice Guideline (2018) · cites this paper as [248]
In the citing paper
“The presence of TARTs is a predictor of infertility (226, 248, 253).”
From Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society* Clinical Practice Guideline (2018) · cites this paper as [248]
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Speiser, P. W., Arlt, W., Auchus, R. J., Baskin, L. S., Conway, G. S., Merke, D. P., Meyer-Bahlburg, H. F. L., Miller, W. L., Murad, M. H., Oberfield, S. E., et al. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01865 · Cited by 1,234
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Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management
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“Male subfertility can also occur as the consequence of TART expansion (16, 20, 21).”
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“However, in cross-sectional studies no correlation of ACTH and TART size could be found, and TARTs even occur in overtreated patients with suppressed ACTH levels (3, 4).”
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“In fact, TARTs even occurred in overtreated patients with suppressed ACTH and 17-hydroxyprogesterone (17-OHP) concentrations (3, 4, 12).”
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Acién, P., & Acién, M. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9113555 · Cited by 92
“[103] also noted that TARTs (likely reflecting undertreatment) contribute to the high prevalence of subfertility in men with CAH and that inhibin B values are important indicators of fertility.”
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Self-citationMANAGEMENT OF ENDOCRINE DISEASE: Gonadal dysfunction in congenital adrenal hyperplasia
Claahsen-van der Grinten, H. L., Stikkelbroeck, N., Falhammar, H., & Reisch, N. (2021) · European Journal of Endocrinology · doi:10.1530/eje-20-1093 · Cited by 72
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Adrenal disorders in pregnancy
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Testicular Adrenal Rest Tumors in Patients With Congenital Adrenal Hyperplasia
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“Our findings confirm and extend previous studies showing reduced fertility in men with CAH.(46) Although some males with CAH may develop hypogonadotropic hypogonadism due to high levels of steroids which suppress the hypothalamicpituitary-gonadal axis, the most common reason for reduced fertility in men with CAH is th…”
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“…521–527 525 but at an older age than men in group Null or A. Recently, Reisch et al. described the presence of TART in two adult CAH patients (aged 37 and 40 years, respectively) who were categorized as having milder mutations (group B), thereby supporting our hypothesis (Reisch et al., 2009).”
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Nonclassic congenital adrenal hyperplasia
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“Periodic screening by scrotal (testicular) ultrasound is warranted (for men with NCAH) because treatment options are limited once irreversible testicular damage due to the mass effect has occurred [45,46].”
BackgroundLong-Term Outcomes of Congenital Adrenal Hyperplasia
Nordenström, A., Lajić, S., & Falhammar, H. (2022) · Endocrinology and Metabolism · doi:10.3803/enm.2022.1528 · Cited by 43
“Thus, also in males with CAH the fertility rate was markedly reduced [38,73,97-100].”
Infertility and Reproductive Function in Patients with Congenital Adrenal Hyperplasia
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“This result supports the current perception that TARTs occur more frequently in patients affected by more severe forms of CAH because these patients are exposed to higher levels of ACTH, which is a possible causative factor for TART development (29,38,40,41).”
Mazzilli, R., Stigliano, A., Delfino, M., Olana, S., Zamponi, V., Iorio, C., Defeudis, G., Cimadomo, D., Toscano, V., & Mazzilli, F. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00335 · Cited by 37
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“Importantly, glucocorticoid overdosing can also result in reduced fecundity due secondary hypogonadism [52].”
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“(3) Patient 12 is still on leuprolide acetate, cyproterone acetate and growth hormone therapy.”
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Self-citationCongenital adrenal hyperplasia in adults
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Congenital adrenal hyperplasia
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“This percentage is higher than that in recent reports [4, 14, 17-19] except for the study of Stikkelbroeck et al.”
BackgroundResultInfluentialChihaoui, M., Kanoun, F., Chaker, F., Yazidi, M., Bouchrit, K., Mizouni, H., Feki, M., Kharrat, M., & Slimane, H. (2016) · Andrologia · doi:10.1111/and.12416 · Cited by 23
“Similarly, the size of a TART can differ according to the type of CAH (Reisch et al., 2009).”
BackgroundResultLong‐term health consequences of congenital adrenal hyperplasia
Pofi, R., Ji, X., Krone, N. P., & Tomlinson, J. (2023) · Clinical Endocrinology · doi:10.1111/cen.14967 · Cited by 28
“34,71 However, the frequency of semen analysis again varies based on clinical judgement.”
Substitution therapy in adult patients with congenital adrenal hyperplasia
Reisch, N. (2014) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2014.11.002 · Cited by 23
Self-citationRecabarren, M. P., Rojas-Garcia, P. P., Einspanier, R., Padmanabhan, V., Sir‐Petermann, T., & Recabarren, S. E. (2013) · Reproduction · doi:10.1530/rep-13-0006 · Cited by 23
“2001, New 2001, Reisch et al .”
Rohayem, J., Bäumer, L. M., Zitzmann, M., Fricke‐Otto, S., Mohnike, K. L., Gohlke, B. C., Reschke, F., Jourdan, C., Muller, H. L., Dunstheimer, D., et al. (2021) · European Journal of Endocrinology · doi:10.1530/eje-20-1154 · Cited by 22
Hormone-Based Treatments in Subfertile Males
Patel, D. P., Chandrapal, J. C., & Hotaling, J. M. (2016) · Current Urology Reports · doi:10.1007/s11934-016-0612-4 · Cited by 22
“Adrenal androgens may also be peripherally aromatized to estrogens, which can also disrupt spermatogenesis [29].”
BackgroundGrowth and Reproductive Outcomes in Congenital Adrenal Hyperplasia
Nebesio, T. D., & Eugster, E. (2010) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2010-298937 · Cited by 22
Auer, M. K., Paizoni, L., Neuner, M., Lottspeich, C., Schmidt, H., Bidlingmaier, M., Hawley, J. M., Keevil, B. G., & Reisch, N. (2021) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2021.105921 · Cited by 24
“In line, presence of TART has been associated with poor treatment quality in some [8] but not all studies [9,40].”
Self-citationRussian clinical practice guidelines «congenital adrenal hyperplasia»
Mokrysheva, N. G., Mel'nichenko, G. A., Adamyan, L. V., Troshina, E. A., Молашенко, Н. В., Игоревна, С. А., Uvarova, E. V., Esayan, E. R. M., Andreeva, E. N., Ужегова, Ж. А., et al. (2021) · Obesity and metabolism · doi:10.14341/omet12787 · Cited by 28
Tanaka, M., Enatsu, N., Chiba, K., & Fujisawa, M. (2018) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12068 · Cited by 20
Challenges Waiting for an Adult with DSD
Nowotny, H. F., & Reisch, N. (2022) · Hormone Research in Paediatrics · doi:10.1159/000527433 · Cited by 24
Self-citationBurman, P., Falhammar, H., Waldenström, E., Sundin, A., & Bitzèn, U. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa870 · Cited by 19
Collet, T., & Pralong, F. P. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2691 · Cited by 19
“The chronological association of TART disappearance with pregnancy suggests that mechanical obstruction on seminal tubules might have caused this patient’s infertility, although gonadal axis suppression may also have contributed to infertility, as discussed recently (3, 4).”
Charfi, N., Kamoun, M., Mnif, M. F., Mseddi, N., Mnif, F., Kallel, N., Naceur, B. B., Rekik, N., Fourati, H., Daoud, E., et al. (2012) · Case Reports in Urology · doi:10.1155/2012/648643 · Cited by 19
Congenital Adrenal Hyperplasia
Vos, A. A., & Bruinse, H. W. (2010) · Obstetrical & Gynecological Survey · doi:10.1097/ogx.0b013e3181d61046 · Cited by 18
“This complication, also known as testicular adrenal rest tumor, occurs in almost all affected males due to adrenal rests in the testes, and is often accompanied by impaired spermatogenesis and Leydig cell failure (41,42).”
Bachelot, A., Lapoirie, M., Dulon, J., Leban, M., Renard Penna, R., & Touraine, P. (2021) · European Journal of Endocrinology · doi:10.1530/eje-20-0787 · Cited by 19
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Kavoussi, P. K., Summers-Colquitt, R. B., Odenwald, K. C., Kressin, M., Kavoussi, K. M., Pool, T. B., & Kavoussi, S. K. (2016) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-016-0665-9 · Cited by 17
“It has even been suggested that glucocorticoid overtreatment may have an adverse effect on spermatogenesis by suppression of the hypothalamic-pituitarygonadal axis, and there may be individual variation in responses [19].”
BackgroundMatsumoto, A. M., & Bremner, W. J. (2011) · Williams Textbook of Endocrinology · doi:10.1016/b978-1-4377-0324-5.00019-5 · Cited by 18
Management of the Adult with Congenital Adrenal Hyperplasia
Auchus, R. J. (2010) · International Journal of Pediatric Endocrinology · doi:10.1155/2010/614107 · Cited by 19
Choi, J., & Yoo, H. (2017) · Korean Journal of Pediatrics · doi:10.3345/kjp.2017.60.2.31 · Cited by 17
Management aspects of congenital adrenal hyperplasia during adolescence and transition to adult care
Balagamage, C., Arshad, A., Elhassan, Y., Said, W. B., Krone, R. E., Gleeson, H. K., & Idkowiak, J. (2023) · Clinical Endocrinology · doi:10.1111/cen.14992 · Cited by 19
The role of imaging in congenital adrenal hyperplasia
Teixeira, S. R., Elias, P. C. L., Andrade, M. T. S., Melo, A., & Elías, J. (2014) · Arquivos Brasileiros de Endocrinologia & Metabologia · doi:10.1590/0004-2730000003371 · Cited by 17
Jha, S., El‐Maouche, D., Marko, J., Mallappa, A., Veeraraghavan, P., & Merke, D. P. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00227 · Cited by 16
“Reduced fecundity is common in men with classic congenital adrenal hyperplasia (CAH) [1].”
BackgroundReproductive health in young male adults with chronic diseases in childhood.
Sanctis, V. D., Soliman, A. T., & Mohamed, Y. (2013) · PubMed · Cited by 16
Gusmano, C., Cannarella, R., Crafa, A., Barbagallo, F., Vignera, S. L., Condorelli, R. A., & Calogero, A. E. (2022) · Journal of Endocrinological Investigation · doi:10.1007/s40618-022-01849-9 · Cited by 17
Schröder, M. A. M., Neacşu, M., Adriaansen, B. P. H., Sweep, F. C. G. J., Ahmed, S. F., Ali, S., Bachega, T. A. S. S., Baronio, F., Birkebæk, N., de Bruin, C., et al. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad143 · Cited by 14
Primary and Secondary Hypogonadism
Santi, D., & Corona, G. (2017) · Endocrinology · doi:10.1007/978-3-319-44441-3_24 · Cited by 14
Auer, M. K., Krumbholz, A., Bidlingmaier, M., Thieme, D., & Reisch, N. (2019) · Neuroendocrinology · doi:10.1159/000504672 · Cited by 13
Self-citationTesticular Adrenal Rest Tumor (TART) in congenital adrenal hyperplasia
Özışık, H., Yürekli, B. Ş., Şimşir, İ. Y., Altun, İ., Soyaltın, U. E., Güler, E., Önay, H., Sarsık, B., & Saygılı, F. (2017) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2017.06.009 · Cited by 11
Sonnet, E., Roudaut, N., & Kerlan, V. (2011) · ISRN Endocrinology · doi:10.5402/2011/219494 · Cited by 11
COVID-19 and its treatments: lights and shadows on testicular function
Pallotti, F., Esteves, S., Faja, F., Buonacquisto, A., Conflitti, A. C., Hirsch, M., Lenzi, A., Paoli, D., & Lombardo, F. (2022) · Endocrine · doi:10.1007/s12020-022-03221-6 · Cited by 8
Vukina, J., Chism, D. D., Sharpless, J. L., Raynor, M., Milowsky, M. I., & Funkhouser, W. K. (2015) · Case Reports in Pathology · doi:10.1155/2015/459318 · Cited by 10
“Thus, the serum testosterone in CAH is a function of the extent of testicular TART expansion [33, 34].”
Background
Metadata
- Authors
- Reisch, N., Flade, L., Scherr, M., Rottenkolber, M., Pedrosa Gil, F., Bidlingmaier, M., Wolff, H., Schwarz, H.-P., Quinkler, M., Beuschlein, F., & Reincke, M.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- LMU Klinikum (DE)
- Psychosomatic Ambulance and Outpatient Clinic (F.P.G.), University Hospital München, D-80336 München, Germany
- München Klinik (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Endocrinology and Metabolism (N.R., L.F., M.B., F.B., M.Re.), University Hospital München, D-80336 München, Germany
- Corresponding author
- Reisch, Nicole
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2009-05-01
- Volume
- 94
- Issue
- 5
- Pages
- 1665-1670
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1981718662
- Cited by
- 170
- References
- 22
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 9 · 2019: 12 · 2018: 6 · 2017: 12 · 2016: 13 · 2015: 12 · 2014: 11 · 2013: 15 · 2012: 15
- FWCI
- 5.72
- 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 › Sexual Differentiation and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- congenital adrenal hyperplasia, male subfertility, testicular adrenal rest tumor, semen quality, hypogonadism, inhibin B, 17-hydroxyprogesterone, salt wasting, simple virilizing CAH, testicular volume
- MeSH terms
- Adrenal Hyperplasia, Congenital, Adrenal Rest Tumor, Adult, Fertility, Follicle Stimulating Hormone, Hormones, Humans, Infertility, Male, Inhibins, Leydig Cells, Luteinizing Hormone, Male, Middle Aged, Saliva, Semen, Sperm Count, Spermatogenesis, Testis, Testosterone, Ultrasonography, Cohort Studies, Treatment Outcome, Young Adult
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