Ovarian function during use of Nestorone(R) subdermal implants

Area of Science:

• Reproductive endocrinology
• Contraception development
• Pharmacokinetics and pharmacodynamics

Background:

• Nestorone progestin (NES), a 19-nor-progesterone derivative, is effective for implant contraception due to its inactivity when taken orally.
• Evaluating ovarian function is crucial for assessing the efficacy and safety of long-acting contraceptive implants.

Purpose of the Study:

• To assess ovarian function, including ovulation and luteal activity, during 24 months of use of one 4-cm or two 3-cm Nestorone progestin (NES) implants.
• To correlate serum Nestorone progestin (NES) levels with ovarian activity and estradiol (E2) and progesterone (P) levels.

Main Methods:

• Sixty volunteers per group received either one 4-cm or two 3-cm NES implants for 24 months.
• Vaginal ultrasound (VUS) and blood sampling for E2, P, and NES levels were conducted bi-weekly for 6 weeks at months 1, 6, 12, 18, and 24.
• Ovarian activity was assessed by VUS, and serum hormone levels were analyzed.

Main Results:

• Serum NES levels decreased over time, stabilizing after 18 months.
• Luteal activity was infrequent (<3%) in the first year but increased in the second year (up to 35% in the 2-implant group).
• Ovulation was not observed when NES levels exceeded 80 pmol/L; persistent anovulatory follicles were common with normal E2 levels.

Conclusions:

• While NES implants are effective, ovulation can occur, particularly in the second year of use.
• Higher serum NES levels are associated with suppressed ovulation.
• A new single NES implant with a higher release rate is being developed to enhance contraceptive efficacy and safety beyond two years.