This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brodie, A. M. H. Articles by Albrecht, E. D. Search for Related Content PubMed PubMed Citation Articles by Brodie, A. M. H. Articles by Albrecht, E. D.

Effect of Treatment with Aromatase Inhibitor 4-Hydroxandrostenedione on the Nonhuman Primate Menstrual Cycle¹

Departments of Pharmacology and Experimental Therapeutics [A. M. H. B., J. O. H., M. G., K. M.] and of Obstetrics and Gynecology [E. D. A.], School of Medicine, University of Maryland, Baltimore, Maryland 21201

4-Hydroxyandrostenedione (4-OHA) is a potent inhibitor of rat ovarian and human placental aromatase activity as assessed in vitro and has been shown to suppress ovarian estrogen secretion in vivo in rats. The compound inhibited extragonadal aromatization in male rhesus monkeys and reduced plasma levels of estradiol in postmenopausal women with advanced, metastatic breast cancer. Furthermore, 4-OHA caused disease remission in these patients. Prior to using this compound in premenopausal patients, the present study was carried out to determine whether 4-OHA affects the menstrual cycle by inhibiting ovarian estrogen production in nonhuman primate species. Four baboons (Papio anabis) exhibiting regular menstrual cycles were studied. Blood samples were collected daily throughout a control menstrual cycle and during treatment with daily s.c. injections of 4-OHA. Menstruation was not observed in three of four animals during treatment and did not resume until cessation of 4-OHA administration. The midcycle surge of estradiol which averaged 411 pg/ml in the control menstrual cycle was reduced during 4-OHA treatment by a mean of 49% of control. Thereafter, with continued 4-OHA treatment, serum concentrations of estradiol were significantly reduced below the basal control level [75.3 ± 5.6 (SE) pg/ml] and were very low or undetectable. Perineal turgescence, an index of estrogenicity, was inhibited by 4-OHA administration. The preovulatory surge of serum luteinizing hormone, which averaged 114 ng/ml during the control cycle, appeared normal in three of four animals following 12 to 14 days of 4-OHA administration, but no luteinizing hormone surge occurred with continued 4-OHA administration. The results indicate that, although 4-OHA reduces ovarian estrogen formation during the first cycle, treatment for a second consecutive cycle appears to be necessary for maximal suppression.

¹ This work was supported by NIH Grant HD-13909 and presented in part at the 1986 Meeting of the Society for the Study of Reproduction and the Third International Congress on Hormones and Cancer, 1987.

² To whom requests for reprints should be addressed, at Department of Pharmacology and Experimental Therapeutics, School of Medicine, University of Maryland, 655 W. Baltimore Street, Baltimore, MD 21201.

Received 3/25/88. Revised 3/ 9/89. Accepted 5/15/89.

This article has been cited by other articles:

				J. T. Sanderson, J. Hordijk, M. S. Denison, M. F. Springsteel, M. H. Nantz, and M. van den Berg Induction and Inhibition of Aromatase (CYP19) Activity by Natural and Synthetic Flavonoid Compounds in H295R Human Adrenocortical Carcinoma Cells Toxicol. Sci., November 1, 2004; 82(1): 70 - 79. [Abstract] [Full Text] [PDF]

				J. M. Cline, G. Soderqvist, T. C. Register, J. K. Williams, M. R. Adams, and B. Von Schoultz Assessment of Hormonally Active Agents in the Reproductive Tract of Female Nonhuman Primates Toxicol Pathol, January 1, 2001; 29(1): 84 - 90. [Abstract] [PDF]

				J. Nakamura, Q. Lu, G. Aberdeen, E. Albrecht, and A. Brodie The Effect of Estrogen on Aromatase and Vascular Endothelial Growth Factor Messenger Ribonucleic Acid in the Normal Nonhuman Primate Mammary Gland J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1432 - 1437. [Abstract] [Full Text]