Biodegradable norethindrone (NET:cholesterol) contraceptive implants: phase II-A: a clinical study in women

Area of Science:

• Reproductive Medicine
• Endocrinology
• Pharmacology

Background:

• Subdermal implants offer a long-acting reversible contraception (LARC) method.
• Norethindrone (NET) is a progestin used in hormonal contraceptives.
• Assessing the safety, efficacy, and biodegradability of novel NET-cholesterol implants is crucial.

Purpose of the Study:

• To evaluate the safety, contraceptive efficacy, and biodegradability of subdermal norethindrone (NET)-cholesterol implants (Anuelle).
• To monitor serum NET levels, hormonal profiles (E2, P, FSH, LH), and lipid profiles in women using the implants.

Main Methods:

• A prospective study involving 19 healthy, sexually active women using either four or five NET-cholesterol pellets.
• Serum NET levels were measured at various time points post-implantation up to 36 months.
• Hormonal profiles (E2, P, FSH, LH), lipid profiles, and adverse events were monitored. Contraceptive efficacy was assessed by pregnancy rates.

Main Results:

• No pregnancies occurred in either the four- or five-pellet group over 36 months.
• Serum NET levels showed an initial "burst-effect" followed by a decline, becoming undetectable by 36 months, confirming biodegradability.
• Anovulatory cycles were observed in 78% (four pellets) and 99% (five pellets) of women. Plasma lipids showed reduced total and LDL cholesterol and triglycerides.
• Irregular bleeding was the primary drug-related adverse effect.

Conclusions:

• Subdermal norethindrone (NET)-cholesterol implants are safe and highly effective contraceptives with complete biodegradability.
• The implants induce anovulation and favorably alter lipid profiles, with irregular bleeding as the main side effect.
• Anuelle implants represent a viable long-acting reversible contraception option.