Depot leuprolide acetate with estrogen and progestin add-back for long-term treatment of premenstrual syndrome

Citations from the literature /International

Journal of Gynecology & Obstetrics 50 (1995) I1 I- 121

estrogen replacement. Methods: Eighty postmenopausal women received 0.625 mg/day of conjugated equine estrogens for 48 weeks. Using a double-masked design, the subjects were randomized to medroxyprogesterone acetate 10 mg/day for 14 days every 28 or 84 days, or the samedosagefor 28 of 84 days. Bleeding patterns, endometrial histology, and serum lipids were assessed.Results:The total days of bleeding during the 48-week study were significantly reduced(P < 0.05) in the women given the progestin for 14 days every 3 months (mean f standard deviation 29 f 16 days) than with the other two regimens. In all groups, secretory endometrium was reported in 17-39s. At 24 but not 48 weeks, simple hyperplasia was observed in one subject in each of the lessthan monthly progestin groups. Significant increases(P < 0.05) of high-density lipoprotein cholesterol were observed before but not after medroxyprogesterone acetate in the women receiving it lessthan monthly. No change was seen with monthly progestin. Conclusions: In this direct comparison, medroxyprogesterone acetate given for I4 days every 3 months elicited less vaginal bleeding than standard monthly administration. Only a single woman had simple hyperplasia with each regimen of progestin given every 84 days. Medroxyprogesterone acetate given for I4 days every 3 months representsa possible alternative to standard monthly therapy if coupled with regular assessmentof the endometrium. Veralipride for hot flu&es induced by a gooadotropin-releasing hormone agonist: A controlled study

Vercellini P.; Sacerdote P.; Trespidi L.; Manfredi B.; Panerai A.E.; Crosignani P.G. ITA

FERTIL. STERIL. 199462/5 (938-942) Objectives: To evaluate the efftcacy of veralipride, a benzamide derivative, in the treatment of hot flushes induced by GnRH agonists (GnRH-a) and to study peripheral blood mononuclear cell -endorphin concentrations during drug administration. Design: Randomized, placebo-controlled, double-blind trial. Setting: Academic department of obstetrics and gynecology. Patients: Forty women of mean age 43 f 5 years who experienceddisturbing hot flushesduring a 4-month courseof tryptorelin depot for myoma-associatedmenorrhagia. Interventions: Treatment with oral veralipride 100 mg/d (20 subjects) or matching placebo (20 subjects) during the third month of GnRH-a administration. Main Outcome Measures: Modifications of frequency and severity of hot flushesas shown by a 0 to 6-point vasomotor scoring system and variations of fi-endorphin levels in peripheral blood mononuclear cells. Results: Two subjectsin each group dropped out of the study. The median (range) vasomotor scoreat the end of the secondmonth of treatment was 4 (3 to 6) in both the veralipride and placebo group. At the end of the third and fourth months the median (range) scoreswere, respectively, 2 (0 to 6) versus4 (I to 6) and 2 (0 to 5) versus4 (I to 6). No significant variations in mononuclear cell fl-endorphin concentrations were recorded. Serum PRL levels rose from II.7 f 5.7 to 132.3 f 65.0 rig/ml (conversion factor to SI unit, 1.0)during veralipride administration and returned to IO.6 f 3.7 @ml after drug withdrawal. Conclusion: Veralipride reduced vasomotor symptoms induced by a GnRH-a. Transient hyperprolactinemia was the main side

119

effect observed. The mode of action of the drug in GnRH-atreated patients and possible interactions with endogenousopioid peptides need further elucidation. Depot leuprolide acetate witb estrogen nod progestin add-back for long-term treatment of premenstrual syndrome

Mezrow G.; Shoupe D.; Spicer D.; Lobo R.; Leung B.; Pike M. USA

FERTIL. STERIL. 19946215(932-937) Objective: To test the effectivenessand safety of long-term depot leuprolide acetate (GnRH-a) plus estrogenand progestin add-back therapy in the treatment of moderate and severepremenstrual syndrome (PMS). Design: A prospective trial with each patient serving as her own control. Setting: University teaching hospital. Participants: Ten women with regular menstrual cycles complaining of moderate to severe PMS. Premenstrual syndrome was diagnosed when symptoms increased z 25% during the luteal phase.Treatment: Four-week cycles of IM injections of placebo or GnRH-a with all patients receiving saline (placebo), the first cycle followed by 12cycles of GnRHa, 7.5 mg. Conjugated equine estrogen(0.625mgid) was started Monday through Saturday within the first cycle and increased as needed.Medroxyprogesterone acetate (MPA), IO mgid, was taken orally for 10 days after 4, 8, and I2 cycles of GnRH-a therapy. Main Outcome Measures: Changes in three symptom categories(water retention, pain, and psychological function), serum levels of total cholesterol and HDL, HDL-2, and LDL cholesterol, E2, and estrone. Endometrial biopsy was obtained I day after the end of the 12th GnRH-a cycle, and bone density was assessedusing quantitative computer tomography at the end of the 12thGnRH-a cycle. Results: During treatment, there was a significant decreasecompared with baseline and placebo in all three symptom categories. There were no significant changesin lipids. Endometrial biopsies revealed progestational changeswith no evidence of hyperplasia. Quantitative computer tomography bone density dropped 3.7 on averagecompared with baseline after I2 months of treatment, but this was not statistically significant. Conclusion: Gonadotropin-releasing hormone agonist therapy with hormonal add-back therapy is effective in treating PMS symptoms with progressive improvement over a 12-monthperiod. This therapy prevents changesin lipids and adequately protects the endometrium with the addition of MPA every 4th cycle. Quantitative computer tomography bone density dropped at I2 months; further examination of bone changesis necessary. A comparative multicenter study of tbe effects of continuous lowdose estradiol released from a new vaginal ring versus estriol vaginal pessaries in postmenopausal women with symptoms and sip of urogenitalatropby

Henriksson L.; Stjernquist M.; Boquist L.; Alander U.; Selinus I. SWE

AM. J. OBSTET. GYNECOL. 1994 171/3(624-632) Objective: Our purpose was to study the efficacy, safety, and acceptability Of a new estradiol-releasing (6.5 to 9.5 pg per 24 h) silicone rubber vaginal ring compared with Ovesterin 0.5 mg estriol vaginal pessaries. Study Design: Gynecologic clinical