Delayed oral estradiol combined with leuprolide increases endometriosis-related pain.
OBJECTIVE
To determine if low-dose estrogen replacement can be added to GnRH agonist therapy after three months to reduce hypoestrogenic symptoms while allowing continued relief of pain in patients with endometriosis.


METHODS
Thirteen women with endometriosis and pain were treated with six months of leuprolide acetate in a prospective, randomized double-blind placebo controlled study. After three months of therapy, six subjects initiated oral estradiol 1 mg daily, and seven received an identical placebo.


RESULTS
Dysmenorrhea improved in both groups, and dyspareunia significantly improved in the GnRH agonist plus placebo group. The mean pain scores of the oral estrogen group tended to be higher than the placebo group, and hot flushes tended to be less severe with estrogen treatment. However, differences observed between the study and placebo groups did not reach statistical significance.


CONCLUSIONS
In a prospective, randomized study, low-dose estrogen replacement increases endometriosis-related pain during GnRH agonist therapy. The study was terminated after the first 13 subjects due to the concerning trend toward recurrent symptoms in women who received oral estradiol during GnRH agonist therapy for endometriosis-related pain. With the trend toward increasing pain with estrogen add-back therapy, a larger study would not seem to be justifiable.
Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, Denver, USA. BSHurst@pop.uky.edu
B S
BS
Hurst
S C
SC
Gardner
K E
KE
Tucker
C A
CA
Awoniyi
W D
WD
Schlaff
D000284:Administration, Oral; D000328:Adult; D002908:Chronic Disease; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004412:Dysmenorrhea / Q000188:drug therapy / Q000209:etiology*; D004715:Endometriosis / Q000150:complications* / Q000188:drug therapy; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage* / Q000009:adverse effects; D010147:Pain Measurement; D011446:Prospective Studies; D013997:Time Factors
D005300:Fertility Agents, Female; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D016729:Leuprolide