Effects of long-term low-dose mifepristone on reproductive function in women

Abstract

Low-dose antiprogestin administration has been proposed as a new contraceptive modality to interference with endometrial receptivity without disturbing ovarian function. The effects of 1 mg/day mifepristone for 150 days on the menstrual cycle were assessed in 21 surgically sterilized women. The aim was to study each woman for one control cycle and during months 1, 3 and 5 of treatment. Ovulation, endometrial thickness, serum oestradiol and progesterone, urinary luteinizing hormone, endometrial morphology and cervical mucus were assessed. Luteal phase progesterone concentrations were observed in 36 of the 60 treated months assessed and less frequently as treatment progressed. The bleeding pattern was regular in most biphasic cycles, while prolonged interbleeding intervals or no bleeding were associated with monophasic cycles. Altered endometrial morphology was found in all cases irrespective of the occurrence of luteal activity. Increased endometrial thickness and dilated glands were observed in 25 and 34% respectively of the monophasic cycles. Mifepristone, 1 mg/day, interferes with endometrial development while allowing the occurrence of biphasic ovarian cycles and regular bleeding. However, it also prevents ovarian cyclicity in a high proportion of treated months, and this is associated with increased endometrial growth in some women, which may be of concern.

Low-dose mifepristone increases uterine natural killer cell cytotoxicity and perforin expression during the receptive phase

“…Previously published studies (20)(21)(22) have shown that low-dose mifepristone might be an effective contraceptive regimen with few side effects. For example, a single-dose (2 mg/kg body weight) administration of mifepristone led to inhibition of implantation without affecting serum steroid hormonal profiles or menstrual cycles in rhesus monkeys (21), and daily administration of mifepristone (1 mg/day) blocked endometrial development while allowing biphasic ovarian cycles and regular bleeding in women (22).…”

“…For example, a single-dose (2 mg/kg body weight) administration of mifepristone led to inhibition of implantation without affecting serum steroid hormonal profiles or menstrual cycles in rhesus monkeys (21), and daily administration of mifepristone (1 mg/day) blocked endometrial development while allowing biphasic ovarian cycles and regular bleeding in women (22). When mifepristone was administered at a concentration of 1 mg/day, the steady plasma level of mifepristone was found to be 65 nmol/L.…”

The human corpus luteum: life cycle and function in natural cycles

“…Evidence of a direct role of PR in human and rat ovarian function has been supported in recent years by the demonstration that [1] the antiprogestin RU486 inhibits ovulation in the human (7) and [2] LH is the primary signal for rupture of preovulatory ovarian follicles and induces a transient expression of PR mRNA for both protein isoforms in granulosa cells isolated from rat preovulatory follicles (7)(8)(9).…”

Inhibition of Proliferation of Endometrial Stromal Cells by Trichostatin A, RU486, CDB-2914, N-Acetylcysteine, and ICI 182780

“…We sought to assess the effects of H 2 O 2 , NAC, RU486, and CDB on the YHES cell proliferation, since their effects on endometrial cell growth have been well documented either in vivo or in vitro [25,26,[54][55][56][57][58][59][60] . Treatment with H 2 O 2 at low concentrations of 1 and 10 M increased cell proliferation by 18 and 22%, respectively, while treatment with a higher concentration of 100 M of H 2 O 2 induced inhibition of proliferation ( fig.…”