The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer

Endocrinology. 1977 Jun;100(6):1684-95. doi: 10.1210/endo-100-6-1684.


4-Hydroxy-f-androstene-3,17-dione (4-OH-A) when tested at various concentrations was found to inhibit markedly the conversion of 4-andorstene-3,17-dione to estrogens inhuman placental and rat ovarian microsomes. To obtain evidence that estrogen biosynthesis could also be reduced in vivo with 4-OH-A, rats were treated sc at a dose level of 50 mg/kg body weight. After 3 h the ovarian veins were cannulated and blood collected. Estradiol concentrations in the plasma were reduced by 80% compared to control values during the proestrous surge and on Day 4 of pregnancy. 4-OH-A was also found to be effective in controlling estrogen-dependent reproductive and neoplastic processes. In rats treated from Day 2-7 of pregnancy, implantation of fertilized ova was completely prevented in some rats, while in others either implantation was delayed or the development of implants was retarded. 4-OH-A treatment of rats having estrogen-dependent breast tumors induced by 7,12-dimethylbenz(a)anthracene caused 80% of the tumors to regress significantly in 4 weeks of treatment; 42% of these regressed completely.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Androstenedione / analogs & derivatives*
  • Androstenedione / metabolism
  • Androstenedione / pharmacology
  • Androstenedione / therapeutic use
  • Animals
  • Aromatase Inhibitors
  • Body Weight
  • Embryo Implantation / drug effects*
  • Estrogens / biosynthesis
  • Female
  • Humans
  • Male
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / drug therapy*
  • Pregnancy
  • Proestrus
  • Rats


  • Aromatase Inhibitors
  • Estrogens
  • Androstenedione
  • 9,10-Dimethyl-1,2-benzanthracene
  • formestane