High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men
Open accessAbstract
Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis (EE) secondary to hypoventilation. Erythropoietin (Epo) and testosterone regulate erythrocyte production. Low thyroid hormone levels are also associated to hypoventilation. Hence, these hormones can play a role in etiopathogeny of EE. The purpose of this study was to elucidate the effect of sexual and thyroid hormones and Epo in residents from Lima (150 m) and Cerro de Pasco (4,340 m), Peru, and the response to human chorionic gonadotrophin stimulation (hCG). Three groups, one at low altitude and two at high altitude [1 with hemoglobin values >16–21 g/dl and the second with Hb ≥21 g/dl (EE)], were studied. hCG was administered intramuscularly in a single dose (1,000 IU), and blood samples were obtained at 0, 6, 12, 24, 48, and 72 h after injection. High-altitude natives present similar levels of gonadotropins and thyroid hormones but lower dehydroepiandrosterone sulphate (DHEAS) levels ( P < 0.01) and greater Epo ( P < 0.01), 17α-hydroxyprogesterone ( P < 0.01), and testosterone levels ( P < 0.01) than those at 150 m. Serum testosterone levels (524.13 ± 55.91 μg/dl vs. 328.14 ± 53.23 ng/dl, means ± SE; P < 0.05) and testosterone/DHEAS ratios are higher (7.98 ± 1.1 vs. 3.65 ± 1.1; P < 0.01) and DHEAS levels lower in the EE group (83.85 ± 14.60 μg/dl vs. 148.95 ± 19.11 ug/dl; P < 0.05), whereas Epo was not further affected. Testosterone levels were highest and DHEAS levels lowest in the EE group at all times after hCG stimulation. In conclusion, high androgen activity could be involved in the etiopathogeny of CMS. This evidence provides an opportunity to develop new therapeutic strategies.
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Increased hematocrit levels are associated with increased risk of adverse cardiovascular events.
“Large epidemiologic studies show that increased hematocrit levels are associated with increased risk of adverse cardiovascular events (39).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [39]
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“Erythropoiesis is a process induced hormonally by erythropoietin and testosterone, which takes effect directly on bone marrow at polychromatophilic erythroblast level and enhances the synthesis of ribosomal RNA.”
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Lèon‐Velarde, F., Rivera, M. C., Huicho, L., & Villafuerte, F. C. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8772-2_22 · Cited by 14 · see citing works
Gonzales, G. F. (2015) · Segurança Alimentar e Nutricional · doi:10.20396/san.v17i1.8634797 · Cited by 12 · see citing works
“En el presente estudio hemos observado que con la menopausia el puntaje de MMC aumenta, lo que indicaría que el estradiol sería protector de la eritrocitosis excesiva, y que la testosterona sería más bien factor de riesgo de MMC como ha sido demostrado recientemente [50].”
BackgroundSelf-citationMountain sickness in altitude inhabitants of Latin America: A systematic review and meta-analysis
Zila-Velasque, J. P., Grados‐Espinoza, P., Romero, P., Tapia‐Sequeiros, G., Pascual-Aguilar, J. E., Ruiz‐Yaringaño, A. J., Sevillano, S. B., Ayca-Mendoza, J., & Nieto-Gutiérrez, W. (2024) · PLoS ONE · doi:10.1371/journal.pone.0305651 · Cited by 11 · see citing works
“We identified lower prevalence of cerebral edema (less than 1 event out of 10 persons), but slightly lower than European estimations (1 event out of 10 persons) [46].”
Background., P., Sharma, V., Sharma, M., Varshney, R. K., Kumar, B., & Sethy, N. K. (2021) · High Altitude Medicine & Biology · doi:10.1089/ham.2020.0187 · Cited by 11 · see citing works
“Andean males with higher levels of testosterone (T) suffer from CMS, a lack of adaptation to altitude characterized by excessive ery-throcytosis (Gonzales et al., 2009, 2011) and increased risk of developing cardiovascular events (Corante et al., 2018).”
Vyas, K. J., Danz, D., Gilman, R. H., Wise, R. A., Lèon‐Velarde, F., Miranda, J. J., & Checkley, W. (2015) · High Altitude Medicine & Biology · doi:10.1089/ham.2015.0026 · Cited by 10 · see citing works
“Point-of-care testing using the HemoCue has been shown to be a reliably accurate alternative to the gold standard methemoglobin test at sea level, 15 and has been used in prior high altitude studies in Peru (Leo´n-Velarde et al., 1994; Gonzales et al., 2009).”
Liu, W., Zhang, X., Liu, J., Pu, L., Ai, L., Xu, H., Wang, G., Wang, D., Song, X., Zhang, Y., et al. (2025) · Cell stem cell · doi:10.1016/j.stem.2025.03.010 · Cited by 9 · see citing works
Efficient breathing at neonatal ages: A sex and Epo-dependent issue
Iturri, P., Bairam, A., & Soliz, J. (2016) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2016.12.004 · Cited by 9 · see citing works
“In line with this evidence, high serum testosterone 5 levels are associated with excessive erythrocytosis in chronic mountain sickness (Gonzales et al., 2009), and testosterone deficiency induces anemia and reduces the responsiveness to erythropoiesis-stimulating agents in men with chronic kidney…”
BackgroundInfluentialMating Behavior Increases Workload of the Heart in Thoroughbred Stallions
HATAZOE, T., Kubota, C., FUJIKI, M., & MISUMI, K. (2011) · Journal of Veterinary Medical Science · doi:10.1292/jvms.11-0360 · Cited by 7 · see citing works
Nutritional status and the gonadotrophic response to a polar expedition
Woods, D. R., Delves, S. K., Britland, S. E., Shaw, A. M., Brown, P. E. H., Bentley, C., Hornby, S. B., Burnett, A., Lanham-New, S. A., & Fallowfield, J. L. (2014) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2014-0418 · Cited by 6 · see citing works
“Furthermore, an increase in testosterone would also be of benefit to erythropoiesis and protein synthesis, which may be advantageous when exercising or undertaking physical work in cold weather (Gonzales et al. 2009).”
Gonzales, G. F. (2025) · Science Progress · doi:10.1177/00368504251387827 · Cited by 5 · see citing works
“55 This imbalance has been documented in both men 35 and women.”
InfluentialSelf-citationCui, J., GAO, L., Hai-jun, Y., Wang, F., Jiang, C., & Gao, Y. (2013) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2013.1388 · Cited by 4 · see citing works
“Excessive erythropoiesis in CMS is a process that is hormonally regulated (15,16).”
Efectos de la suplementación con testosterona sobre el rendimiento en resistencia
Fernández-Díaz, P., & Domínguez, R. (2016) · Revista Andaluza de Medicina del Deporte · doi:10.1016/j.ramd.2015.02.011 · Cited by 3 · see citing works
Zaman, G. S., Alshahrani, S. A. S. A.-S., Laskar, N. B., Hadadi, I., Alelyani, M., Adam, M., Babiker, M., Musa, M. J., Barua, P., & Mohammed, M. E. A. (2022) · International Journal of General Medicine · doi:10.2147/ijgm.s344904 · Cited by 3 · see citing works
“Since 17α-hydroxyprogesterone is elevated at high altitude with respect to sea level, this could be another reason for this.(14) However, previous studies reported an insignificant difference in the increase and decrease in the blood testosterone of smokers.”
BackgroundUNNOTICED ETIOLOGY IN ORTHOPEDIC COMPLAINTS: CHRONIC MOUNTAIN SICKNESS
Karaytuğ, K., Ekinci, M., & Yücekul, A. (2022) · Journal of Istanbul Faculty of Medicine / İstanbul Tıp Fakültesi Dergisi · doi:10.26650/iuitfd.929597 · Cited by 2 · see citing works
Alcantara-Zapata, D. E., Thiersch, M., & Gonzales, G. F. (2023) · PubMed Central · doi:10.5167/uzh-233787 · Cited by 2 · see citing works
Self-citationHemoglobina y testosterona: importancia en la aclimatación y adaptación a la altura
Gonzales, G. F. (2011) · Revista Peruana de Medicina Experimental y Salud Pública · doi:10.17843/rpmesp.2011.281.462 · Cited by 1 · see citing works
“Recientemente se ha demostrado que los varones de Cerro de Pasco con eritrocitosis excesiva tienen mayores niveles séricos de testosterona que aquellos viviendo en la misma altitud pero sin eritrocitosis excesiva (12).”
InfluentialSelf-citationImportance of Testosterone on Adaptation at High Altitude
Gonzales, G. F. (2018) · International Journal of Medical and Surgical Sciences · doi:10.32457/ijmss.2015.043 · Cited by 1 · see citing works
Self-citationTiedemann, J. (2012) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-12132
Testosterone replacement therapy
Vrolyk, M. (2015) · OpenBU (Boston University)
Serum Levels of Testosterone in Patients with Polycythemia Vera
Fujita, H., Ohwada, A., & Nishimura, S. (2016) · Open Journal of Blood Diseases · doi:10.4236/ojbd.2016.62004
UNNOTICED ETIOLOGY IN ORTHOPEDIC COMPLAINTS: CHRONIC MOUNTAIN SICKNESS
Karaytuğ, K., Ekinci, M., & Yücekul, A. (2022) · Journal of Istanbul Faculty of Medicine / İstanbul Tıp Fakültesi Dergisi · doi:10.26650/iuitfd.2022.929597
Yang, M., Zhu, Y., Liu, L., Pan, C., Li, L., Su, Q., Zhou, W., Fu, L., Yang, L., Luo, F., et al. (2026) · Journal of Global Health · doi:10.7189/jogh.16.04042
- Authors
- Gonzales, G. F., Gasco, M., Tapia, V., & Gonzales-Castañeda, C.
- Affiliations
- Universidad Peruana Cayetano Heredia (PE)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2009-06
- Volume
- 296
- Issue
- 6
- Pages
- E1319-E1325
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC2692401
- OpenAlex
- W2101044947
- Cited by
- 51
- References
- 58
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 4 · 2018: 1 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 6 · 2012: 2
- FWCI
- 1.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Universidad Peruana Cayetano Heredia Institutional Repository (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health
- Fogarty International Center (D43TW005746)
- National Institute for Occupational Safety and Health
- Agency for Toxic Substances and Disease Registry
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › High Altitude and Hypoxia
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- chronic mountain sickness, erythrocytosis, testosterone, dehydroepiandrosterone sulfate, erythropoietin, human chorionic gonadotropin stimulation, thyroid hormones, androgenic activity, high altitude, hypoxia, erythropoiesis, 17-hydroxyprogesterone, hyperventilation, high-altitude adaptation
- MeSH terms
- Adult, Aged, Altitude, Altitude Sickness, Chronic Disease, Erythrocytes, Erythropoietin, Estradiol, Hematocrit, Hemoglobins, Humans, Male, Middle Aged, Peru, Polycythemia, Testosterone, Dehydroepiandrosterone Sulfate, 17-alpha-Hydroxyprogesterone
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