Depot leuprolide acetate with estrogen and progestin add-back for long-term treatment of premenstrual syndrome.
OBJECTIVE
To test the effectiveness and safety of long-term depot leuprolide acetate (GnRH-a) plus estrogen and progestin add-back therapy in the treatment of moderate and severe premenstrual syndrome (PMS).


METHODS
A prospective trial with each patient serving as her own control.


METHODS
University teaching hospital.


METHODS
Ten women with regular menstrual cycles complaining of moderate to severe PMS. Premenstrual syndrome was diagnosed when symptoms increased > or = 25% during the luteal phase.


METHODS
Four-week cycles of IM injections of placebo or GnRH-a with all patients receiving saline (placebo), the first cycle followed by 12 cycles of GnRH-a, 7.5 mg. Conjugated equine estrogen (0.625 mg/d) was started Monday through Saturday within the first cycle and increased as needed. Medroxyprogesterone acetate (MPA), 10 mg/d, was taken orally for 10 days after 4, 8, and 12 cycles of GnRH-a therapy.


METHODS
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 1 day after the end of the 12th GnRH-a cycle, and bone density was assessed using quantitative computer tomography at the end of the 12th GnRH-a cycle.


RESULTS
During treatment, there was a significant decrease compared with baseline and placebo in all three symptom categories. There were no significant changes in lipids. Endometrial biopsies revealed progestational changes with no evidence of hyperplasia. Quantitative computer tomography bone density dropped 3.7 on average compared with baseline after 12 months of treatment, but this was not statistically significant.


CONCLUSIONS
Gonadotropin-releasing hormone agonist therapy with hormonal add-back therapy is effective in treating PMS symptoms with progressive improvement over a 12-month period. This therapy prevents changes in lipids and adequately protects the endometrium with the addition of MPA every 4th cycle. Quantitative computer tomography bone density dropped at 12 months; further examination of bone changes is necessary.
Mezrow
G
G
Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles, California.
Shoupe
D
D
Spicer
D
D
Lobo
R
R
Leung
B
B
Pike
M
M
D000328:Adult; D015519:Bone Density; D003692:Delayed-Action Preparations; D004717:Endometrium / Q000473:pathology; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000008:administration & dosage / Q000627:therapeutic use*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000627:therapeutic use*; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage / Q000627:therapeutic use*; D011293:Premenstrual Syndrome / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011446:Prospective Studies
D003692:Delayed-Action Preparations; D004967:Estrogens; D004970:Estrone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D016729:Leuprolide