Hormone replacement therapy may prevent the development of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement

Scand J Rheumatol. 2006 Nov-Dec;35(6):468-71. doi: 10.1080/03009740600844498.


Background: Isolated pulmonary hypertension (iPHT) is a near-fatal consequence of systemic sclerosis (SSc); in female patients, the risk of its development is increased during the post-menopausal period, when the protective effects of oestrogens on the endothelium decrease. In many animal and human models, hormone replacement therapy (HRT) and oestrogen administration proved efficacious in counteracting many mechanisms that might be implicated in the pathogenesis of iPHT. Accordingly, it has been hypothesized that HRT might help to prevent the development of iPHT.

Methods: A retrospective cohort study was conducted on 61 SSc patients with the limited cutaneous form of the disease and no sign of pulmonary hypertension on echocardiogram (pulmonary artery pressure, PAP > 35 mmHg) at the time of menopause. All the patients had to be stably treated with calcium-channel blockers and not to have risk factors for secondary PHT throughout the duration of the observational period.

Results: Twenty patients (32.8%) received HRT for a mean of 6.7 +/- 3.7 years. None of these patients developed iPHT after a mean of 7.2 +/- 3.5 years from menopause, whereas eight out of 41 patients not receiving HRT (19.5%) developed iPHT after a similar time period (7.5 +/- 3.9 years, p = 0.032). These rates were not explained by differences between the two groups with respect to autoantibodies, age, age at onset of SSc, diffusing capacity of the lung for carbon monoxide (DLCO) at menopause, or duration of therapy with calcium-channel blockers.

Conclusion: HRT administration may be effective in SSc post-menopausal women, preventing the development of iPHT.

MeSH terms

  • Estrogen Replacement Therapy*
  • Estrogens / therapeutic use*
  • Ethinyl Estradiol / therapeutic use*
  • Female
  • Humans
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / prevention & control*
  • Middle Aged
  • Retrospective Studies
  • Scleroderma, Limited / complications*


  • Estrogens
  • Ethinyl Estradiol