Efficacy of depot leuprolide in premenstrual syndrome: effect of symptom severity and type in a controlled trial.
OBJECTIVE
To determine whether depot leuprolide is effective in premenstrual syndrome (PMS) and whether symptom type or severity affects therapeutic or hormonal responses and the incidence of adverse events.


METHODS
Twenty-five women who met strict diagnostic criteria for PMS completed a double-blind, placebo-controlled, 6-month crossover trial at a university medical center. Depot leuprolide (3.75 mg/month) or saline was administered intramuscularly for three consecutive treatment cycles. Efficacy, adverse events, and hormone concentrations were assessed at each visit. Repeated-measures analysis of variance was used to analyze continuous data, and ordinal and binary data were analyzed using nonparametric techniques.


RESULTS
Depot leuprolide treatment was significantly more effective than placebo on all rating scales. Irritability, neurologic symptoms, breast tenderness, and fatigue were most responsive to treatment. Symptoms were reduced to follicular phase levels only in women without premenstrual depression. Those with moderate premenstrual depression improved but remained clinically symptomatic, whereas the group with severe premenstrual depression showed no improvement on any efficacy measure. Adverse events were lowest in those without premenstrual depression and highest in those with severe depression. Leuprolide suppressed estradiol and progesterone in most premenstrual depression groups but had varying effects on gonadotropins.


CONCLUSIONS
Leuprolide treatment reduced both behavioral and physical symptoms and was well tolerated in the absence of severe premenstrual depression. Women should be evaluated for depression severity before receiving a GnRH agonist. The differential response to leuprolide suggests that it may possess diagnostic value in determining distinct subtypes of PMS.
Brown
C S
CS
Department of Clinical Pharmacy, University of Tennessee, Memphis.
Ling
F W
FW
Andersen
R N
RN
Farmer
R G
RG
Arheart
K L
KL
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D003863:Depression / Q000188:drug therapy / Q000209:etiology; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007273:Injections, Intramuscular; D016729:Leuprolide / Q000008:administration & dosage* / Q000009:adverse effects; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D011293:Premenstrual Syndrome / Q000097:blood / Q000188:drug therapy*; D011374:Progesterone / Q000097:blood
D003692:Delayed-Action Preparations; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D016729:Leuprolide