Objective: To evaluate the efficacy of a combination of bioidentical combined 17β-estradiol and progesterone transdermal delivery system (lipophilic emulsion-type base) to relieve climacteric symptoms. The hormonal replacement was given during a period of 6 months at four different cyclic doses to mimic the normal ovary secretory pattern.
Design: An open, randomized, comparative, between-patient trial conducted over 6 months in 29 menopausal women with climacteric symptoms assessed with the Kupperman index at baseline and during treatments. Saliva and serum values of 17β-estradiol and progesterone were quantitated before treatment and after 3 and 6 months. Pharmacokinetic data following transdermal administration of 17β-estradiol (0.3 mg, daily) and progesterone (100 mg, daily) were calculated from saliva levels using high-performance liquid chromatography analysis.
Results: Improvement in climacteric symptoms was reported in 93% of women evaluated before and after 3 and 6 months of treatment. Values of saliva 17β-estradiol increased after 6 months from 0.6 ± 0.3 pg/mL to 14.1 ± 3.3 pg/mL, and the values of serum 17β-estradiol increased from 3.3 ± 2.8 pg/mL to 80.6 ± 21.9 pg/mL. Of responders, 88% characterized symptom relief as complete. No adverse health-related events were attributed to the bioidentical hormone therapy. Time to maximum saliva concentrations (Tmax), in all experimental cases, was observed after 6 hours. Baseline values were reached within 24 hours, indicating a diurnal rhythm of 17β-estradiol seen in normally cyclic women over the 24-hour period, ie, its daily biological rhythm.
Conclusion: Percutaneous absorption of 17β-estradiol, as well as the absorption of progesterone, was associated with relief of climacteric symptoms. The cyclical transdermal delivery of combined bioidentical hormones may be advantageous because it mimics the secretory profiles of 17β-estradiol and progesterone in normally cyclic women over a 28-day period. Larger studies are needed to determine the long-term effects of our therapy.
Keywords: 17β-estradiol; circadian rhythms; estrogen homeostasis; menopause; transdermal.