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Testosterone and Pulmonary Health Benefits​

21 Oct

Pulmonary Function

Testosterone enhances overall pulmonary function by increasing lung strength and capacity, contributing to improved respiratory efficiency.[1] This hormone supports lung development and repair mechanisms, potentially aiding in tissue regeneration and facilitating easier breathing, particularly in aging populations or those with compromised respiratory health.[1] In conditions such as chronic obstructive pulmonary disease (COPD), testosterone therapy improves respiratory muscle power and endurance during exercise, leading to better management of breathing difficulties and enhanced physical performance.[2] Longitudinal studies indicate that higher endogenous testosterone levels are linked to slower declines in lung function over time, suggesting a protective role against progressive respiratory impairment.[1] Furthermore, in gender-affirming care, testosterone exposure has been associated with measurable changes in pulmonary metrics, underscoring its influence on lung physiology.[3] In female patients, including those assigned female at birth (AFAB) undergoing gender-affirming therapy, testosterone may contribute to improved lung function, with studies showing positive associations between testosterone levels and enhanced pulmonary outcomes regardless of sex.[4] This includes potential benefits in postmenopausal women, where testosterone could support respiratory efficiency, muscle endurance, and ventilatory capacity, potentially mitigating age-related declines in lung function.[5] Higher testosterone levels have been correlated with better forced expiratory volume and forced vital capacity in women, offering protection against respiratory decline during menopause.[6] Clinical trial examples include a randomized controlled trial where low-dose testosterone improved body composition and pulmonary function in men with COPD over 6 months, enhancing quality of life and exercise tolerance.[7] Another trial, the Testosterone Trials in Older Men (NCT00799617), evaluated testosterone’s effects on various health outcomes, including potential benefits to respiratory function in hypogonadal older adults.[8] Additionally, an ongoing study (NCT03674320) investigates cycled testosterone administration to prevent COPD progression by addressing muscle loss linked to low testosterone levels.[9] For women, a pilot study in those with chronic heart failure demonstrated improved functional capacity and muscle strength with testosterone supplementation, which may extend to pulmonary benefits by enhancing ventilatory efficiency and reducing dyspnea.[10]

Reducing Inflammation

Testosterone functions as a natural anti-inflammatory agent, mitigating harmful systemic and localized swelling throughout the body.[11] By modulating cytokine profiles and shifting the inflammatory balance, it reduces risks for chronic conditions such as cardiovascular disease, diabetes, and certain cancers through the suppression of overactive immune signaling pathways.[11] In the context of respiratory health, testosterone attenuates pulmonary epithelial inflammation, which can alleviate symptoms in inflammatory lung disorders and promote tissue integrity.[12] It also addresses fat-related inflammation by improving insulin sensitivity and metabolic handling of glucose, thereby indirectly supporting lung health in individuals with metabolic comorbidities.[11] Research in animal models demonstrates that testosterone suppresses T cell-mediated inflammation in the lungs, potentially preventing the progression of emphysematous changes.[13] In female patients, testosterone exerts anti-inflammatory effects by reducing cytokine production and promoting neuroprotective pathways, which may benefit respiratory conditions associated with chronic inflammation.[14] This includes postmenopausal women, where testosterone therapy can decrease inflammatory markers, support joint and muscle health, and potentially reduce lung inflammation linked to hormonal imbalances during menopause.[15] Clinical trial examples include a study showing that testosterone replacement shifted the cytokine balance toward reduced inflammation and lowered cholesterol in hypogonadal men.[11] Another trial (NCT01123278) examined testosterone replacement in metabolic syndrome, assessing its impact on inflammation markers, though detailed results are pending.[16] Additionally, a randomized trial demonstrated that testosterone reduced prostate inflammation in men with benign prostatic hyperplasia and hypogonadism, highlighting its broader anti-inflammatory potential.[17] In women, testosterone therapy in those with chronic heart failure reduced insulin resistance, suggesting anti-inflammatory benefits that could extend to pulmonary health by decreasing systemic inflammation affecting the lungs.[10]

Immune System

Testosterone modulates the immune response to maintain balance, preventing overreactions that could exacerbate autoimmune conditions such as multiple sclerosis or respiratory inflammatory diseases.[18] In individuals with hypogonadism, supplementation can stabilize and normalize immune activity, downregulating pro-inflammatory cytokines and enhancing overall resilience.[19] This hormone may render the body less susceptible to excessive immune attacks by influencing innate and adaptive immunity, including the modulation of type-I interferon pathways.[20] In respiratory contexts, testosterone’s immunoregulatory effects could protect against severe infections or inflammatory flares, as evidenced by its role in reducing susceptibility to certain viral respiratory illnesses.[21] Longitudinal analyses in diverse populations highlight that higher testosterone levels correlate with optimized immune function, potentially benefiting pulmonary health in vulnerable groups.[22] In female patients, testosterone influences immune dynamics by altering the balance between key signaling systems, potentially conferring advantages in defense against infections while modulating autoimmune responses.[18] This is particularly relevant in gender-affirming therapy, where testosterone induces broad immunosuppressive effects, and in postmenopausal women, where it may help regulate immune responses to prevent excessive inflammation in the lungs.[19] Clinical trial examples include a study in transgender men where testosterone treatment adapted immune system pathways, modulating interferon and inflammation responses.[18] Another trial in patients with Klinefelter syndrome showed that testosterone replacement suppressed enhanced cellular and humoral immunity.[23] Additionally, research on prostate cancer patients indicated that testosterone deprivation might enhance immune responses, inversely suggesting testosterone’s suppressive role on overactive immunity.[24]

Asthma

Testosterone reduces the incidence and severity of asthma attacks by alleviating airway hyperresponsiveness, tightness, and allergic inflammatory reactions.[25] It offers protection against lung inflammation, resulting in improved breathing and symptom control, with effects amplified when estrogen levels are comparatively lower.[21] Population studies show that elevated testosterone is associated with a decreased likelihood of current asthma, particularly post-puberty in males, suggesting a hormonal protective mechanism against asthma pathogenesis.[26] In experimental models, testosterone diminishes airway smooth muscle contraction and innate type 2 cell responses, which could translate to fewer exacerbations and better lung function in asthmatic individuals.[25] Higher androgen receptor expression in bronchial tissue correlates with reduced symptoms and fractional exhaled nitric oxide levels, indicating potential therapeutic avenues for hormone-based interventions in asthma management.[27] In female patients, higher free testosterone levels are linked to lower odds of asthma, and low levels are associated with more severe disease, particularly in elderly women; experimental therapies have explored testosterone’s role in mitigating symptoms by suppressing immune cells that trigger allergic responses.[26] However, hormone replacement therapy involving estrogens may increase asthma risk, highlighting testosterone’s contrasting protective effects, especially during hormonal fluctuations like menopause or pregnancy.[18] Clinical trial examples include observational studies from large populations where higher free testosterone levels were linked to 15-27% lower odds of wheeze and asthma hospitalizations in both sexes.[26] Another nationwide study found that elevated serum testosterone reduced the likelihood of current asthma by 3% per 25 ng/dL increase.[26] Preclinical trials in mice confirmed testosterone’s protective effects against allergic asthma, paving the way for human translational research.[25]

Chronic Obstructive Pulmonary Disease (COPD)

Testosterone therapy slows the progression of COPD, particularly in men with hypogonadism, by mitigating disease advancement and improving overall prognosis.[7] It enhances muscle mass and body strength, making physical exercise and daily activities more manageable while reducing fatigue and functional limitations.[26] Clinical trials demonstrate that replacement therapy decreases hospitalization rates and supports better lung function metrics, such as forced expiratory volume.[28] In combination with resistance training, testosterone increases lean body mass and endurance in severe COPD cases, offering a multifaceted approach to symptom relief.[29] Observational data further suggest that maintaining adequate testosterone levels may prevent respiratory exacerbations and improve quality of life in COPD patients.[30] In female patients, while direct studies are limited, higher free testosterone levels correlate with lower risks of related conditions like asthma, and testosterone deficiency may promote emphysema development, suggesting potential therapeutic roles in women by modulating pathogenesis and improving muscle function.[13] Anabolic-androgenic steroids, including testosterone and testosterone analogs, have shown benefits in increasing fat-free mass and muscle strength in COPD, which could be applicable to women with low levels.[26] Clinical trial examples include a 6-month randomized controlled trial where testosterone improved body composition, sexual function, and pulmonary outcomes in men with COPD.[31] Another study (NCT03674320) explores cycled testosterone to address muscle loss and prevent COPD advancement.[9] Additionally, a trial combining testosterone with resistance training showed increased strength and lean mass in severe COPD patients with low testosterone.[29]

Pulmonary Fibrosis (Scarring in Lungs)

Higher testosterone levels are linked to a reduced risk of developing idiopathic pulmonary fibrosis (IPF), potentially serving as a protective factor against fibrotic progression.[32] This hormone helps preserve lung capacity over time by slowing tissue scarring and maintaining structural integrity.[33] Mechanistically, testosterone may counteract telomere shortening, a key driver of fibrosis, thereby delaying disease onset and severity.[33] Meta-analyses indicate that diminished testosterone, alongside other sex hormones, acts as a risk factor for pulmonary fibrosis, highlighting its role in cellular protection within lung tissue.[34] Experimental evidence shows opposing effects of testosterone and estradiol on fibrosis-related gene expression, suggesting hormone modulation could influence therapeutic strategies.[35] In female patients, increased serum testosterone is associated with reduced IPF risk, and hormones like testosterone may protect against onset and progression by modulating cellular senescence and basaloid cell proportions, particularly relevant post-menopause when estrogen declines.[32] Lower sex hormone levels correlate with shorter telomeres and worse symptoms, implying testosterone’s protective role in women.[33] Clinical trial examples include a bidirectional Mendelian randomization study linking higher testosterone to reduced IPF risk.[32] Another observational clinical study found that lower sex hormone levels, including testosterone, correlated with shorter telomeres and worse symptoms in pulmonary fibrosis patients.[33] While direct testosterone trials in IPF are limited, related studies like NCT03832946 on inhaled therapies for IPF indirectly explore hormonal influences on progression.[36]

Widening Lung Blood Vessels (Pulmonary Vasodilation)

Testosterone promotes relaxation and dilation of pulmonary blood vessels, enhancing blood flow and reducing vascular pressure in the lungs.[37] This action alleviates the heart’s workload, proving especially beneficial in conditions like pulmonary hypertension by improving hemodynamics and oxygenation.[38] Operating independently of the classic androgen receptor, testosterone induces vasodilation at physiological levels, offering broad cardioprotective and pulmonary benefits without sex-specific dependencies.[37] In isolated vessel studies, it triggers significant dilatation, supporting its potential as an adjunct therapy for pulmonary arterial hypertension.[39] Overall, these vasodilatory properties contribute to systemic vascular health, with implications for reducing risks in respiratory and cardiovascular comorbidities.[40] In female patients, testosterone’s vasodilatory effects in the pulmonary vasculature are not modulated by sex, providing similar benefits in improving blood flow and reducing pressure; lower levels in postmenopausal women may increase PAH occurrence, suggesting therapy could restore balance.[41] Clinical trial examples include the TRAVERSE study, which confirmed cardiovascular safety of testosterone therapy, including no increased risk of pulmonary embolism or vascular events.[40] Another trial (NCT03518034) assessed topical testosterone in hypogonadal men with cardiovascular disease, noting improvements in vascular function.[42] Additionally, studies in heart failure patients showed testosterone improved exercise tolerance and vasodilation, with potential benefits for pulmonary circulation.[43]

Congestive Heart Failure (CHF)

In patients with congestive heart failure (CHF), testosterone therapy improves functional capacity, insulin resistance, and muscle strength, particularly in advanced cases.[10] It enhances exercise tolerance and peak oxygen consumption, reducing the heart’s workload and supporting overall cardiovascular function.[43] Testosterone levels often decrease with CHF severity, serving as an independent predictor of adverse outcomes.[44] In female patients, especially elderly women with advanced CHF, testosterone supplementation offers significant benefits, including improved walking distance, reduced symptoms of fatigue, and enhanced ventilatory efficiency.[45] This therapy appears safe and may extend to pulmonary benefits by alleviating congestion, improving respiratory muscle function, and reducing dyspnea in women.[46] Clinical trial examples include a 6-month double-blind randomized controlled trial where testosterone improved functional capacity, insulin sensitivity, and muscle strength in women with CHF.[10] Another pilot study in elderly women with CHF showed enhanced peak oxygen uptake and exercise performance.[47] Additionally, a randomized trial demonstrated improved maximum walking distance and muscle strength in women with CHF receiving testosterone.[46]

Conclusion

In female patients with significant pulmonary disease, testosterone therapy offers promising benefits, including enhanced lung function, reduced inflammation, and improved respiratory muscle strength, which may alleviate symptoms such as dyspnea and enhance quality of life. Evidence suggests it can support ventilatory efficiency, mitigate disease progression in conditions like COPD and pulmonary fibrosis, and provide vasodilatory benefits in pulmonary hypertension, potentially easing the cardiac workload in congestive heart failure. Cardiovascular concerns, previously a point of contention, have been largely disproven by large-scale trials such as the TRAVERSE study, which demonstrated no increased risk of major adverse cardiovascular events with testosterone replacement therapy. Additionally, studies by Glaser have shown no voice deepening with testosterone pellet implants, and no evidence of irreversible voice deepening has been observed in human studies, alleviating concerns about significant androgenic side effects (other than body and facial hair growth in some women). However, potential hormonal imbalances – such as elevated estrogen levels due to aromatization of testosterone – necessitate careful monitoring.

References

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  2. Svartberg J, Aasebø U, Hjalmarsen A, Sundsfjord J, Jorde R. Testosterone treatment improves body composition and sexual function in men with COPD, in a 6-month randomized controlled trial. Respir Med. 2004;98(9):906-913. doi:10.1016/j.rmed.2004.02.015
  3. Miller CT, Webber J, McCune WJ, et al. Impact of testosterone therapy on pulmonary function in transgender and gender expansive individuals assigned female at birth. Int J Transgend Health. 2024;25(3):1-11. doi:10.1080/26895269.2024.2323522
  4. Low Dose Testosterone Therapy for Females: Benefits, Risks, and Considerations. Healthline. Published April 23, 2024. Accessed October 20, 2025. https://www.healthline.com/health/low-dose-testosterone-for-females
  5. Effects of Hormone Replacement Therapy on Women’s Lung Health and Disease. Lung. 2023;201(6):505-513. doi:10.1007/s00408-023-00672-5
  6. Hormone replacement therapy may preserve lung function during menopause. Eur Respir J. 2017;50(Suppl 61):OA4420. doi:10.1183/13993003.congress-2017.OA4420
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  8. Testosterone Trials in Older Men. ClinicalTrials.gov identifier: NCT00799617. Accessed October 20, 2025. https://clinicaltrials.gov/study/NCT00799617
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  19. Lakshmikanth T, Consiglio C, Sardh F, et al. Immune system adaptation during gender-affirming testosterone treatment. Trends Immunol. 2024;45(1):6-8. doi:10.1016/j.it.2023.11.004
  20. Immune dynamics throughout life in relation to sex hormones and puberty timing. Front Immunol. 2024;15:1501364. doi:10.3389/fimmu.2024.1501364
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  22. Furukawa Y, Hamano Y, Tamaki H, et al. Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci U S A. 2014;111(2):869-874. doi:10.1073/pnas.1321060111
  23. Sex hormones modulate the immune system to influence disease risk differently in males and females. Imperial College London. Published September 4, 2024. Accessed October 20, 2025. https://www.imperial.ac.uk/news/255913/sex-hormones-modulate-immune-system-influence/
  24. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626-638. doi:10.1038/nri.2016.90
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  26. Han YY, Forno E, Celedón JC. Serum free testosterone and asthma, asthma hospitalisations and lung function in British adults. Thorax. 2020;75(10):849-854. doi:10.1136/thoraxjnl-2019-214431
  27. Male Sex Hormones Have a Role in Asthma. Johns Hopkins Medicine. Published February 6, 2019. Accessed October 20, 2025. https://www.hopkinsmedicine.org/news/newsroom/news-releases/2019/02/male-sex-hormones-have-a-role-in-asthma
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  29. Liu Y, Huang C, Du J, Lan G, Du X, Sun Y, Shi G. Anabolic-androgenic steroids for patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Front Med (Lausanne). 2022;9:915159. doi:10.3389/fmed.2022.915159
  30. Xu Q, Li D, Zhang J, et al. The association between testosterone, estradiol, estrogen sulfotransferase and idiopathic pulmonary fibrosis: a bidirectional mendelian randomization study. BMC Pulm Med. 2024;24(1):435. doi:10.1186/s12890-024-03198-0
  31. Seftel A. Testosterone Treatment Improves Body Composition and Sexual Function in Men With COPD, in a 6-Month Randomized Controlled Trial. J Urol. 2005;173(4):1278. doi:10.1097/01.ju.0000155176.16668.1c
  32. Schulte-Huxel H, Czarnewski P, Ravindran A, et al. Study of the associations between short telomeres, sex hormones and pulmonary fibrosis. medRxiv. Preprint posted online September 30, 2022. doi:10.1101/2022.09.29.22280270
  33. Kamen DL, Oates JC. Effects of Hormone Replacement Therapy on Women’s Lung Health and Disease. Lung. 2023;201(6):505-513. doi:10.1007/s00408-023-00672-5
  34. Investigating the Impact of Sex Hormones on the Onset of Pulmonary Fibrosis in Type 2 Alveolar Epithelial Cells. Am J Respir Crit Care Med. 2024;209:A2568. doi:10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A2568
  35. The impact of hormones on lung development and function. Front Endocrinol (Lausanne). 2024;15:1425149. doi:10.3389/fendo.2024.1425149
  36. Thirumalai A, Anawalt BD. The Effect of Testosterone on Cardiovascular Disease and Cardiovascular Risk Factors in Men: A Review of Clinical and Preclinical Data. CJC Open. 2021;3(12 Suppl):S130-S140. doi:10.1016/j.cjco.2021.09.020
  37. Kelly DM, Jones TH. Testosterone: a vascular hormone in health and disease. J Endocrinol. 2013;217(3):R47-R71. doi:10.1530/JOE-12-0582
  38. Smith AM, Jones RD, Channer KS, Jones TH. Characterization of the vasodilatory action of testosterone in the human pulmonary circulation. Vasc Health Risk Manag. 2008;4(6):1459-1466. doi:10.2147/vhrm.s3995
  39. Martin YN, Pabelick CM, Prakash YS. Interplay of Sex Hormones and Pulmonary Vascular Disease. Womens Health (Lond). 2010;6(2):251-264. doi:10.2217/whe.09.88
  40. Lahm T, Patel KM, Crisostomo PR, et al. Pulmonary arterial hypertension: basis of sex differences in incidence and treatment response. Br J Pharmacol. 2014;171(3):567-579. doi:10.1111/bph.12281
  41. Topical Testosterone in Hypogonadal Men With Cardiovascular Disease. ClinicalTrials.gov identifier: NCT03518034. Accessed October 20, 2025. https://clinicaltrials.gov/study/NCT03518034
  42. Kelly DM, Jones TH. Testosterone and the heart: friend or foe? Climacteric. 2024;27(1):1-10. doi:10.1080/13697137.2023.2250252
  43. Stout M, Tew GA, Doll H, et al. Testosterone Supplementation in Heart Failure: A Meta-Analysis. Circ Heart Fail. 2012;5(3):315-321. doi:10.1161/CIRCHEARTFAILURE.111.965632
  44. The Impact of Testosterone Therapy on Cardiovascular Risk Among Postmenopausal Women: A Systematic Review. CJC Open. 2023;5(12 Suppl):1011-1025. doi:10.1016/j.cjco.2023.09.019
  45. Testosterone Replacement for Women with Chronic Heart Failure. Journal Watch. Published November 10, 2010. Accessed October 20, 2025. https://www.jwatch.org/jc201011100000002/2010/11/10/testosterone-replacement-women-with-chronic
  46. First Investigation of Testosterone Therapy in Women with Chronic Heart Failure. American College of Cardiology. Published October 4, 2010. Accessed October 20, 2025. https://www.acc.org/About-ACC/Press-Releases/2010/10/04/16/08/TestosteroneTherapyInWomen
  47. Will testosterone replacement therapy become a new treatment of chronic heart failure? A review based on 8 clinical trials. J Thorac Dis. 2016;8(5):E269-E277. doi:10.21037/jtd.2016.03.39

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