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Obesity and GnRH action. Report of a case with contribution by peripherally derived estrogens
L M Hansen1, F R Batzer, S L Corson
1Department of Obstetrics and Gynecology, Thomas Jefferson University School of Medicine, Philadelphia, Pennsylvania, USA.
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.
Case:
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.
Conclusion:
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.
Insights
Obesity can limit the effectiveness of gonadotropin-releasing hormone agonists (GnRH-a) in treating uterine fibroids. Peripheral estrogen production in adipose tissue may maintain normal hormone levels despite GnRH-a therapy.
Area of Science:
- Endocrinology
- Gynecology
- Reproductive Medicine
Background:
- Gonadotropin-releasing hormone agonists (GnRH-a) suppress pituitary gonadotropin release, reducing ovarian estrogen production.
- This hypoestrogenic state typically shrinks uterine leiomyomas and reduces bleeding.
- Peripheral adipose tissue is a significant source of circulating estrogen, independent of pituitary control.
Observation:
- A morbidly obese woman with uterine leiomyomas experienced persistent menorrhagia despite depot leuprolide acetate (GnRH-a) treatment.
- Her serum estradiol levels remained normal, with suppressed follicle-stimulating hormone (FSH).
- A GnRH stimulation test showed suppressed FSH but unchanged estradiol levels.
Findings:
- Peripheral estrogen synthesis from adrenal androgens in adipose tissue can bypass GnRH-a's pituitary suppression.
- Leuprolide acetate did not effectively lower estradiol levels in this obese patient.
- Morbid obesity may provide a substantial reservoir for continuous peripheral estrogen production.
Implications:
- Patient body habitus is a critical factor when prescribing GnRH suppressants.
- Obesity may necessitate alternative or adjunctive therapies for conditions like uterine leiomyomas.
- Understanding peripheral estrogen sources is crucial for managing hormone-dependent conditions in obese individuals.