Pulmonary Arterial Hypertension: Basis of Sex Differences in Incidence and Treatment Response

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2013 Jun 28

PMID 23802760

Citations 68

Authors

K M Mair

A K Z Johansen

A F Wright

E Wallace

M R MacLean

Affiliations

Soon will be listed here.

Abstract

Pulmonary arterial hypertension (PAH) is a complex disease characterized by elevated pulmonary arterial pressure, pulmonary vascular remodelling and occlusive pulmonary vascular lesions, leading to right heart failure. Evidence from recent epidemiological studies suggests the influence of gender on the development of PAH with an approximate female to male ratio of 4:1, depending on the underlying disease pathology. Overall, the therapeutic strategy for PAH remains suboptimal with poor survival rates observed in both genders. Endogenous sex hormones, in particular 17β oestradiol and its metabolites, have been implicated in the development of the disease; however, the influence of sex hormones on the underlying pathobiology remains controversial. Further understanding of the influence of sex hormones on the normal and diseased pulmonary circulation will be critical to our understanding the pathology of PAH and future therapeutic strategies. In this review, we will discuss the influence of sex hormones on the development of PAH and address recent controversies.

Citing Articles

RPL39 Was Associated With Sex Differences in Pulmonary Arterial Hypertension.

Wang H, Li L, Zhou G, Wang L, Wu Z Can Respir J. 2025; 2025:7139235.

PMID: 39957991 PMC: 11824382. DOI: 10.1155/carj/7139235.

Sex-Specific Differences in Chronic Thromboembolic Pulmonary Hypertension Treated with Balloon Pulmonary Angioplasty.

Kurzyna P, Witowicz A, Kedzierski P, Florczyk M, Banaszkiewicz M, Szwed P J Clin Med. 2025; 14(3).

PMID: 39941569 PMC: 11818403. DOI: 10.3390/jcm14030899.

Relevance of patient-centered actigraphy measures in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: a qualitative interview study.

Kendrew R, Ajraoui S, Beaudet A, Kelly K, Kiely D, Rothman A BMC Pulm Med. 2024; 24(1):608.

PMID: 39696200 PMC: 11654380. DOI: 10.1186/s12890-024-03442-7.

Harmonising cellular conversations: decoding the vital roles of extracellular vesicles in respiratory system intercellular communications.

Jadamba B, Jin Y, Lee H Eur Respir Rev. 2024; 33(174).

PMID: 39537245 PMC: 11558538. DOI: 10.1183/16000617.0272-2023.

Trends and patterns in pulmonary arterial hypertension-associated hospital admissions among methamphetamine users: a decade-long study.

Husein A, Boullion J, Hossain M, Xing D, Khan M, Bhuiyan M Front Cardiovasc Med. 2024; 11:1445193.

PMID: 39529971 PMC: 11550945. DOI: 10.3389/fcvm.2024.1445193.

References

MASI A . Editorial: Pulmonary hypertension and oral contraceptive usage. Chest. 1976; 69(4):451-3. DOI: 10.1378/chest.69.4.451b. View

Miyauchi T, Yanagisawa M, Iida K, Ajisaka R, Suzuki N, Fujino M . Age- and sex-related variation of plasma endothelin-1 concentration in normal and hypertensive subjects. Am Heart J. 1992; 123(4 Pt 1):1092-3. DOI: 10.1016/0002-8703(92)90734-d. View

Christman B, McPherson C, Newman J, King G, Bernard G, GROVES B . An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 1992; 327(2):70-5. DOI: 10.1056/NEJM199207093270202. View

Murray F, MacLean M, Insel P . Role of phosphodiesterases in adult-onset pulmonary arterial hypertension. Handb Exp Pharmacol. 2011; (204):279-305. DOI: 10.1007/978-3-642-17969-3_12. View

Humbert M, Sitbon O, Yaici A, Montani D, OCallaghan D, Jais X . Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J. 2010; 36(3):549-55. DOI: 10.1183/09031936.00057010. View

Chaouat A, Coulet F, Favre C, Simonneau G, Weitzenblum E, Soubrier F . Endoglin germline mutation in a patient with hereditary haemorrhagic telangiectasia and dexfenfluramine associated pulmonary arterial hypertension. Thorax. 2004; 59(5):446-8. PMC: 1746994. DOI: 10.1136/thx.2003.11890. View

Dwyer N, Kilpatrick D . Bosentan for the treatment of adult pulmonary hypertension. Future Cardiol. 2010; 7(1):19-37. DOI: 10.2217/fca.10.114. View

Matori H, Umar S, Nadadur R, Sharma S, Partow-Navid R, Afkhami M . Genistein, a soy phytoestrogen, reverses severe pulmonary hypertension and prevents right heart failure in rats. Hypertension. 2012; 60(2):425-30. PMC: 4252152. DOI: 10.1161/HYPERTENSIONAHA.112.191445. View

Ahn B, Park H, Cho H, Lee H, Lee Y, Yang E . Estrogen and enalapril attenuate the development of right ventricular hypertrophy induced by monocrotaline in ovariectomized rats. J Korean Med Sci. 2003; 18(5):641-8. PMC: 3055117. DOI: 10.3346/jkms.2003.18.5.641. View

10.

Barrett-Connor E, Khaw K, Yen S . A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986; 315(24):1519-24. DOI: 10.1056/NEJM198612113152405. View

11.

Rabinovitch M . Molecular pathogenesis of pulmonary arterial hypertension. J Clin Invest. 2008; 118(7):2372-9. PMC: 2439479. DOI: 10.1172/JCI33452. View

12.

Benza R, Miller D, Barst R, Badesch D, Frost A, McGoon M . An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012; 142(2):448-456. DOI: 10.1378/chest.11-1460. View

13.

Thorne S, Nelson-Piercy C, MacGregor A, Gibbs S, Crowhurst J, Panay N . Pregnancy and contraception in heart disease and pulmonary arterial hypertension. J Fam Plann Reprod Health Care. 2006; 32(2):75-81. DOI: 10.1783/147118906776276486. View

14.

Smith A, Bennett R, Jones T, Cowen M, Channer K, Jones R . Characterization of the vasodilatory action of testosterone in the human pulmonary circulation. Vasc Health Risk Manag. 2009; 4(6):1459-66. PMC: 2663441. DOI: 10.2147/vhrm.s3995. View

15.

Filardo E, Quinn J, Bland K, Frackelton Jr A . Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF. Mol Endocrinol. 2000; 14(10):1649-60. DOI: 10.1210/mend.14.10.0532. View

16.

Giaid A, Yanagisawa M, Langleben D, Michel R, Levy R, Shennib H . Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med. 1993; 328(24):1732-9. DOI: 10.1056/NEJM199306173282402. View

17.

Weiss B, Zemp L, Seifert B, Hess O . Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996. J Am Coll Cardiol. 1998; 31(7):1650-7. DOI: 10.1016/s0735-1097(98)00162-4. View

18.

Badesch D, Raskob G, Elliott C, Krichman A, Farber H, Frost A . Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2009; 137(2):376-87. DOI: 10.1378/chest.09-1140. View

19.

Dubey R, Oparil S, Imthurn B, Jackson E . Sex hormones and hypertension. Cardiovasc Res. 2002; 53(3):688-708. DOI: 10.1016/s0008-6363(01)00527-2. View

20.

Homma N, Nagaoka T, Morio Y, Ota H, Gebb S, Karoor V . Endothelin-1 and serotonin are involved in activation of RhoA/Rho kinase signaling in the chronically hypoxic hypertensive rat pulmonary circulation. J Cardiovasc Pharmacol. 2007; 50(6):697-702. DOI: 10.1097/FJC.0b013e3181593774. View