Treatment of menopausal symptoms with three low-dose continuous sequential 17β-estradiol/progesterone parenteral monthly formulations using novel non-polymeric microsphere technology

Abstract

Objective: To analyze the short-term efficacy and safety over menopausal symptoms of three low-dose continuous sequential 17β-estradiol (E)/progesterone (P) parental monthly formulations using novel non-polymeric microspheres. Methods: This was a multicenter, randomized, single blinded study in which peri- and postmenopausal women were assigned to receive a monthly intramuscular injection of 0.5 mg E + 15 mg P (Group A, n = 34), 1 mg E + 20 mg P (Group B, n = 24) or 1 mg E + 30 mg P (Group C, n = 26) for 6 months. Primary efficacy endpoints included mean change in the frequency and severity of hot flushes and the effect over urogenital atrophy symptoms at 3 and 6 months. Safety variables included changes in the rate of amenorrhea, endometrial thickness and histopathology, and local and systemic adverse events. Results: Compared to baseline at month 6, the three treatment schemes significantly decreased the rate of urogenital atrophy symptoms and the frequency (mean number per day) and severity (mean number graded as moderate and severe per month) of hot flushes. No differences in studied efficacy parameters were observed between studied groups at baseline or at the end of the study. For all groups the most frequent adverse event was pain at the injection site; however they were all rated as mild. At the end of the study peri- and postmenopausal women displayed no significant changes in endometrial thickness or histopathology in all treated groups. The rate of amenorrhea at the end of the study decreased for all studied groups yet was less evident among postmenopausal women as compared to perimenopausal ones. Conclusions: The three low-dose continuous sequential intramuscular monthly treatments of E/P using novel microsphere technology were effective at reducing menopausal symptoms at short-term with a low rate of adverse events. More long-term and comparative research is warranted to support our positive findings.

Variation in menopausal vasomotor symptoms outcomes in clinical trials: a systematic review

“…Of these, 330 were excluded; 59 included fewer than 20 women per study arm and 54 were not an RCT; 126 did not clearly state a sample size calculation; 52 did not measure vasomotor symptoms as the primary outcome; 39 were secondary analysis. Following these exclusions, 214 RCT were included…”

The Current Strategy in Hormonal and Non-Hormonal Therapies in Menopause—A Comprehensive Review

“…Another combination of estrogen therapy uses the intravaginal fractional CO2 laser for treating symptoms related to genito-urinary syndrome [ 19 , 20 , 34 , 35 ]. The combined estrogen-progesterone scheme decreased the rate of urogenital atrophy symptoms and the frequency and severity of hot flushes [ 36 ]. Another study shows that vitamin E may be an alternative to vaginal estrogen [ 26 ].…”

Quality of Life and Menopause

“…Providing a combination of E/P in a parenteral monthly formulation with the presently suggested lower dosages and using a new technology that offers persistent plasmatic levels over time, will have a positive long-term outcome on compliance. It has just reported an optimistic pilot experience in taking care of vasomotor and urogenital atrophy symptoms with three low-dose continuous sequential monthly parenteral formulations of 17b-estradiol (E)/progesterone (P) employing innovative non-polymeric microsphere technology [25]. Later was presented the short-term effect of the same proposed schemes over secondary endpoints (menopausal symptoms and QoL).…”