(R)-Moxestrol

Sprague-Dawley (female, 50-55 days old, DMBA-induced mammary carcinoma)^[1]

2 μg; 8 μg; 24 μg

i.p.; daily; 4 weeks

Exhibited little effect on tumor number or total tumor area, caused a slight increase in average tumor size due to 11 new tumors developing, and showed no significant reduction in [³H]E₂, [³H]R5020, or ¹²⁵I-labeled ovine PRL receptor levels in tumor tissue at 2 μg daily.
Inhibited tumor number by 45% compared to controls, had minimal effect on total tumor area, caused a slight increase in average tumor size due to 4 new tumors developing, showed no significant reduction in [³H]E₂, [³H]R5020, or ¹²⁵I-labeled ovine PRL receptor levels in tumor tissue, and increased plasma PRL levels relative to controls at 8 μg daily.
Reduced tumor number by 65% compared to controls, caused marked reduction in total tumor area and average tumor size (only 3 new tumors developed), reduced [³H]E₂ binding in tumor tissue from 2.3 pmoles/g (controls) to 0.3 pmoles/g, significantly reduced ¹²⁵I-labeled ovine PRL specific binding in tumor tissue, resulted in low progesterone receptor levels in 4 of 6 tumors accompanying reduced estrogen and prolactin receptor levels, and increased plasma PRL levels relative to controls at 24 μg daily.

Sprague-Dawley (female, 200-225 g, with 2-3 prior 4-day estrous cycles)^[2]

0.1-50 μg (various regimens)

s.c.; twice daily; 2-4 days; s.c.; single dose; s.c.; twice on single day

Caused a 1-day delay in vaginal cornification with 0.5 μg twice-daily 4-day treatment.
Caused a 4.5 day delay in vaginal cornification with 5.0 μg twice-daily 4-day treatment.
Caused a 14.8 day delay in vaginal cornification with 50 μg twice-daily 4-day treatment.
Caused a 1.6 day delay in vaginal cornification with 0.5 μg twice-daily 2-day (estrus + diestrus 1) treatment.
Caused a 1.1 day delay in vaginal cornification with 1.5 μg twice-daily 2-day (estrus + diestrus 1) treatment.
Caused a 4.9 day delay in vaginal cornification with 4.5 μg twice-daily 2-day (estrus + diestrus 1) treatment.
Caused a 5.8 day delay in vaginal cornification with 13.5 μg twice-daily 2-day (estrus + diestrus 1) treatment.
Reduced uterine weight to 522 mg (0.5 μg), 358 mg (1.5 μg), 372 mg (4.5 μg), 327 mg (13.5 μg) at 1600 h on expected proestrus (control: 756 mg) with twice-daily 2-day (estrus + diestrus 1) treatment.
Reduced uterine weight to 489 mg (0.5 μg), 362 mg (1.5 μg), 282 mg (4.5 μg), 294 mg (13.5 μg) at 1000 h on expected estrus (control: 453 mg) with twice-daily 2-day (estrus + diestrus 1) treatment.
Completely inhibited ovulation (0/10 rats ovulating) with all doses ≥0.5 μg twice-daily 2-day (estrus + diestrus 1) treatment (control: 10/10).
Reduced plasma LH to 407 ng/mL (control: 888 ng/mL) with 0.5 μg twice-daily estrus-only treatment.
Reduced plasma LH to 103 ng/mL, plasma PRL to 23 ng/mL (control: 203 ng/mL), and uterine weight to 426 mg (control: 590 mg) with 2.5 μg twice-daily estrus-only treatment.
Completely inhibited the preovulatory LH and FSH peaks with 5 μg single dose injected at 2000 h proestrus, 0800 h estrus, or 2000 h estrus.
Depressed the plasma LH response to LHRH by 60% with 0.5 μg twice-daily 2-day (estrus + diestrus 1) treatment.
Almost completely inhibited the plasma LH response to LHRH with doses ≥ 1.5 μg twice-daily 2-day (estrus + diestrus 1) treatment.

Swiss mice (immature 18-day old female)^[3]

1 μg; 10 μg; 100 μg (single s.c.); 1 μg; 3 μg; 10 μg (daily s.c. x3); 30 μg (total s.c. over 3 days); 3 μg; 10 μg (continuous silastic implant over 72 hours)

s.c. (single injection); s.c. (daily for 3 consecutive days); silastic implant (continuous release over 72 hours)

Increased uterine wet weight to a similar extent as 1 μg estradiol or moxestrol at 6 hours, but returned to control levels by 48 hours with a single 10 μg s.c. dose.
Maintained uterine weight increase for 48 hours with a single 100 μg s.c. dose.
Produced maximum uterine weight increase within 24 hours with three daily 1-3 μg s.c. doses, with no further effect from subsequent injections.
Required a daily 10 μg s.c. dose to match the effect of 0.1 μg estradiol.
Increased uterine weight 8-10-fold over 72 hours with silastic implants releasing 3 μg or 10 μg.
Depleted cytosolic ER by 1 hour, increased nuclear ER, and allowed cytosolic ER replenishment to control or above levels by 24 hours with a single 1 μg s.c. dose.
Kept cytosolic ER levels low for at least 24 hours with a single 100 μg s.c. dose.
Induced a 24-hour PR increase similar to estradiol, but PR levels returned to control by 48 hours with a single 1 μg s.c. dose.
Maintained PR at 3-4 times control at 48 hours, dropping to twice control by day 3 and control by day 5 with a single 100 μg s.c. dose.
Inhibited the estradiol-induced uterine weight increase by 30%, and antagonized estradiol-induced ER replenishment and PR induction with a total 30 μg s.c. dose over 3 days; lower doses were ineffective.