Obesity and GnRH action. Report of a case with contribution by peripherally derived estrogens.
BACKGROUND
Gonadotropin-releasing hormone agonists (GnRH-a) are effective in reducing the pituitary release of gonadotropins, which, in turn, decrease ovarian steroidogenesis. The resulting menopausal state decreases the volume and vascular supply to uterine leiomyomas. Peripheral adipose tissue also contributes significantly to the circulatory estrogen pool, which is formed independent of pituitary function. As such, obesity may interfere with depot leuprolide acetate effects, allowing normal estrogen levels despite gonadotropin suppression.


METHODS
A premenopausal, morbidly obese woman was referred for treatment of menorrhagia and uterine leiomyomas. Despite administration of depot leuprolide, a GnRH-a, she continued to bleed heavily. Serum estradiol levels remained in the normal range, with suppression of follicle-stimulating hormone (FSH) levels. The desired hypoestrogenic effect from GnRH-a administration was thought to be negated by estradiol levels arising from peripherally derived conversion of adrenal androgens in adipose tissue. A GnRH stimulation test was performed to evaluate the responsiveness of the pituitary to the above therapy. While FSH was suppressed and unresponsive to stimulation, estradiol remained unchanged.


CONCLUSIONS
Peripheral production of estrogen appears to be unaffected by leuprolide administration. Consideration should be given to the patient's body habitus when administering a GnRH suppressant. Morbidly obese patients possess an unlimited reservoir for peripheral estrogen synthesis.
Hansen
L M
LM
Department of Obstetrics and Gynecology, Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania, USA.
Batzer
F R
FR
Corson
S L
SL
Bello
S
S
D000273:Adipose Tissue / Q000502:physiology; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy*; D016729:Leuprolide / Q000627:therapeutic use*; D008595:Menorrhagia / Q000188:drug therapy*; D008875:Middle Aged; D009767:Obesity, Morbid / Q000503:physiopathology*; D014594:Uterine Neoplasms / Q000188:drug therapy*
D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D007987:Gonadotropin-Releasing Hormone; D016729:Leuprolide