Transdermal application of steroid hormones for contraception.
The concept of transdermal delivery (TD) for steroid application has nowadays been largely accepted for hormone replacement therapy in the menopause. It is only recently that the same concept has been envisaged for contraception. The skin can be penetrated by both estrogens and progestins, provided they are delivered in an appropriate solvent. About 10% of the total dose applied topically is actually absorbed. The transdermal delivery systems (TDS) presently available are either of the reservoir type (membrane-moderated system) or of the matrix dispersion type where the drug is dispersed into a polymer matrix. Estradiol (E2) is the most appropriate steroid for TD and can be combined with progestins to ensure a contraceptive effect. Only potent progestins should be used to achieve effective plasma levels with low doses in order to maintain an acceptable small surface of TDS. TDS changed weekly and delivering both E2 and levonorgestrel (L-NG) at daily dosages of 38.4 (+/- 7.5) and 28.8 (+/- 7.2) micrograms/10 cm2 per day respectively, showed ovulation suppression. Another progestin derived from norprogesterone (ST 1435) has been shown to penetrate the skin when suspended in acetylated lanolin or dissolved in a hydroalcoholic gel and to ensure ovulation suppression at a dose of 2 mg per day in a small number of cycles. These preliminary data demonstrate the feasibility of suppressing ovulation in women by transdermal absorption of steroids. Using TDS for contraception implies that such systems should be perfectly adhesive, well tolerated locally and achieve nearly 100% efficacy. These targets are very challenging, however, the potential advantages are so high that the concept deserves further development.
Sitruk-Ware
R
R
Medical and Clinical Development Department, CIBA-GEIGY Ltd, Basle, Switzerland.
D000042:Absorption; D000279:Administration, Cutaneous; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D004058:Diffusion; D004958:Estradiol / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D006801:Humans; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism; D000077563:Norethindrone Acetate; D009653:Norprogesterones / Q000008:administration & dosage / Q000378:metabolism; D012867:Skin / Q000378:metabolism
D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D009653:Norprogesterones; D004958:Estradiol; C029167:ST 1435; D000077563:Norethindrone Acetate; D009640:Norethindrone