Cocaine impairs ovarian response to exogenous gonadotropins in nonhuman primates.
OBJECTIVE
Determine whether cocaine directly impairs ovarian steroid production and ovulation.


METHODS
Normally cycling adult female rhesus monkeys received daily intravenous normal saline (control; n = 8) or cocaine (4 mg/kg; n = 8) through the follicular phase. Monkeys were injected daily with human menopausal gonadotropin (hMG; Pergonal) at a dose of 6 IU/kg intramuscularly beginning on cycle day 2. Daily blood samples were obtained, and serum estradiol (E(2)) and progesterone (P(4)) were measured by radioimmunoassay. When serum levels of E(2) declined, plateaued, or exceeded 600 pg/mL, laparoscopy was performed to count the number of follicles. If no new corpus luteum was present, monkeys were injected intramuscularly with 1000 IU of hCG. Laparoscopy was repeated 2 days later to document the number of ovulatory stigma.


RESULTS
During ovarian stimulation, cocaine-treated monkeys required an average additional 1.5 days of hMG injections (P =.01), and this resulted in a greater total dose of hMG compared with control monkeys (351 +/- 16 IU versus 297 +/- 15 IU [mean +/- standard error of the mean], P =.03). For spontaneous and hCG-triggered ovulation, the number of ovulatory stigma was significantly lower (P <.003) in the cocaine-treated versus control monkeys (16 versus 31). Peak E(2) levels were significantly (P =.05) lower in cocaine-treated monkeys compared with controls. Luteal phase P(4) levels were lower in the cocaine-treated monkeys, but the difference was not statistically significant when compared with controls.


CONCLUSIONS
Cocaine impaired ovarian responsiveness to exogenous gonadotropins and decreased ovulatory stigma in nonhuman primates. These findings suggest that cocaine has direct ovarian effects.
Thyer
A C
AC
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, The University of Texas Health Science Center at San Antonio, 78229-3900, USA.
King
T S
TS
Moreno
A C
AC
Eddy
C A
CA
Siler-Khodr
T M
TM
Schenken
R S
RS
D000818:Animals; D003042:Cocaine / Q000009:adverse effects / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000503:physiopathology; D004347:Drug Interactions; D004958:Estradiol / Q000097:blood; D005260:Female; D005498:Follicular Phase / Q000187:drug effects / Q000502:physiology; D008253:Macaca mulatta; D008596:Menotropins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects*; D010062:Ovulation Induction; D011374:Progesterone / Q000097:blood; D011897:Random Allocation
D011374:Progesterone; D004958:Estradiol; D008596:Menotropins; D003042:Cocaine