Low-dose Oral or Non-oral Hormone Therapy: Effects on C-reactive Protein and Atrial Natriuretic Peptide in Menopause

Objective: To assess the effects of oral low-dose and non-oral hormone therapy (HT) on ultra-sensitive C-reactive protein (CRP), atrial natriuretic peptide (ANP), and cardiovascular risk factors in postmenopause.

Methods: In this randomized, cross-over study, 44 recently postmenopausal women, with no clinical evidence of cardiovascular disease, received oral low-dose HT (estradiol 1 mg + drospirenone 2 mg/day) for 3 months. Forty-two patients received non-oral, conventional HT (1.5 mg/day percutaneous 17β-estradiol gel or equivalent for nasal route) for 3 months followed by 200 mg/day micronized progesterone by the vaginal route (14 days during each menstrual period). After 3 months, patients were crossed over without washout. Post-HT vs. pre-HT measures were determined: lipids, glucose, body mass index, waist circumference, fibrinogen, CRP-stratified levels, and ANP levels. The study was registered at clinical trials.gov (NCT01432028).

Results: The mean age was 51 ± 3 years and the mean time since the menopause was 22 ± 10 months. CRP-stratified high levels decreased in a higher number of non-oral HT patients, who moved to intermediate and low levels (p = 0.02). No effect of HT was observed on ANP levels (baseline 67.4 (18.4-104.5), low-dose oral 43.5 (14.4-95.9), non-oral 39.8 (15.5-67.5) pg/ml). Markers of endothelial function did not worsen with either low-dose oral or non-oral HT: von Willebrand factor (baseline 118 ± 37%, low-dose oral 119 ± 38%, non-oral 108 ± 3%, p < 0.01), fibrinogen (baseline 356 ± 58 mg/dl; low-dose oral 343 ± 77 mg/dl; non-oral 326 ± 71 mg/dl, p < 0.01).

Conclusions: Low-dose oral and non-oral HT for 6 months had neutral or beneficial effects in recently postmenopausal women with no clinical evidence of cardiovascular disease.