Estradiol suppression and recovery during leuprolide acetate treatment in women as determined weekly by an ultrasensitive recombinant cell bioassay

Citation
Ka. Larmore et Ko. Klein, Estradiol suppression and recovery during leuprolide acetate treatment in women as determined weekly by an ultrasensitive recombinant cell bioassay, GYNECOL END, 14(6), 2000, pp. 405-410
Citations number
11
Categorie Soggetti
Reproductive Medicine
Journal title
GYNECOLOGICAL ENDOCRINOLOGY
ISSN journal
09513590 → ACNP
Volume
14
Issue
6
Year of publication
2000
Pages
405 - 410
Database
ISI
SICI code
0951-3590(200012)14:6<405:ESARDL>2.0.ZU;2-Q
Abstract
We studied the time frame of suppression and recovery of estradiol after in jection with leuprolide acetate utilizing an ultrasensitive recombinant cel l bioassay for estradiol in eight normal premenopausal women. Previous stud ies have shown suppression of gonadotropins and estradiol at 4 weeks after the depot injection, but no studies have shown the weekly time course of es tradiol suppression or recovery. Four women received one 3.75 mg i.m. injec tion of leuprolide acetate and four received two 3.75 mg doses of leuprolid e acetate 4 weeks apart. Estradiol, luteinizing hormone (LH) and follicle-s timulating hormone (FSH) levels were measured weekly for 8 to 12 weeks. Est radiol was significantly suppressed to 26.6 +/- 19.3% of baseline values by week 3 after the initial dose of leuprolide acetate and suppressed to 2.7 +/- 3.1% of baseline values by week 4 (p < 0.02 versus baseline). The actua l values were less than 14.7 pmol/l (4 pg/ml) in all women by week 4. Estra diol remained suppressed for 8 weeks after one dose of leuprolide acetate a nd remained suppressed for 6 weeks after a second dose administered 4 weeks later. LH and FSH followed a similar pattern, but only remained suppressed for 7 weeks after one dose of leuprolide acetate and for 6 weeks after two doses. Estradiol levels at baseline were significantly correlated with bod y mass index (BMI). We also studied one postmenopausal woman. Her baseline estradiol levels were 10.3 pmol/l (2.8 pg/ml) and were suppressed to 3.9 pm ol/l (1.1 pg/ml) by 2 weeks after leuprolide acetate. In conclusion, estradiol war suppressed to postmenopausal levels by the end of the first month of reatment with leuprolide acetate, as determined by a n ultrasensitive bioassay. Higher doses would need to be tested to determin e whether greater suppression can be achieved. The hypothalamic-pituitary-g onadal axis begins to recover 7 weeks after one dose and 6 weeks after a se cond dose of leuprolide acetate. This confirms the adequacy of 4-week dosin g to maintain estradiol and gonadotropin suppression in adult women treated with leuprolide acetate, but raises the question whether less frequent dos ing may be possible in some situations, or whether higher doses may be need ed in some situations for an even greater degree of estradiol suppression.