Evaluation of the tolerability, hormonal profile and endometrial effects of allopregnanolone, administered in the form of a gel by the vaginal route to postmenopausal women on oral estrogen therapy: phase II study.

Author(s)

Paula Andrea de Albuquerque Salles Navarro

• Document type: Master's Dissertation
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2000-07-31

Examining board members

Rui Alberto Ferriani; César Eduardo Fernandes; Marcos Felipe Silva de Sá

• Advisor: Rui Alberto Ferriani

Abstract

Objectives: To evaluate the tolerability and to obtain preliminary data regarding the endometrial effects of allopregnanolone, administered in the form of a gel by the vaginal route to postmenopausal women on oral estrogen therapy, along two cycles of treatment, and to obtain preliminary data about the effect of the drug under study on serum gonadotropin, estradiol and progesterone levels. Patients and methods: Thirteen postmenopausal women were divided into 2 groups: group 1: the first 7 patients admitted to the study (median age = 52 years; median time of amenorrhea = 2 years), and group 2: last 6 patients (median age = 55.5 years; median time of amenorrhea = 4.3 years). All patients were submitted to 2 consecutive treatment cycles of 28 days each continuously taking 2 mg estradial valerate a day by the oral route in combination with 8% allopregnanolone gel by the vaginal route during the last 10 days of a single cycle (group 1) or of 2 cycles (group 2). All patients were evaluated in terms of adverse effects and genital bleeding. Blood samples were collected for hormonal measurements and endometrial biopsies were taken on the 28th and 56th days of treatment in group 1 patients and only on the 56th day in group 2 patients. Results: The rate of compliance with treatment was 100% for the patients of both groups. Mastalgia was the most frequent adverse effect (4 cases), followed by headache and by abdominal pain (2 cases each), all of them related to the use of estradiol valerate. One patient reported vaginal pruritus during the use of the allopregnanolone gel by the vaginal route. All adverse effects were mild and none of them interfered with the use of the prescribed medications. There was no significant difference (P = 1.0) between the proportions of genital bleeding due to hormonal deprivation after one (23.1%) or two cycles of allopregnanolone (33.3%). Also, no significant difference (P = 0.27) was found between the proportions of secretory and proliferative endometrium after one (57.1% and 42.9%, respectively) or two cycles (16.7% and 66.6%) of allopregnanolone. However, there was an apparent reduction in the percentage of secretory endometrium after 2 months of allopregnanolone compared to a single cycle of this drug. There was no significant difference between serum FSH, LH, estradiol or progesterone levels after one cycle with estradiol valerate exclusively, compared to one or two cycles of allopregnanolone. Conclusions: We observed good tolerability of vaginal administration of allopregnanolone gel to menopausal women on oral estrogen treatment with estradiol valerate, as shown by the low incidence of adverse effects and by the good acceptability of treatment. Apparently allopregnanolone does not interfere with serum gonadotrophin, estradiol or progesterone levels. Studies on a larger series and with a longer follow-up time are needed to determine the endometrial effects of this new drug and consequently the possibility of its future use in the different schemes of hormonal replacement therapy currently available. (AU)