Transdermal application of steroid hormones for contraception

Autor: Régine Sitruk-Ware
Rok vydání: 1995
Předmět:
Zdroj: The Journal of Steroid Biochemistry and Molecular Biology. 53:247-251
ISSN: 0960-0760
DOI: 10.1016/0960-0760(95)00055-5
Popis: 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.The transdermal delivery of steroids (TD) is gaining ground in hormone replacement therapy during menopause. This approach to treatment, however, has only recently been envisaged for contraception. Delivered in the appropriate solvent, both estrogens and progestins can penetrate the skin. Approximately 10% of any total dose applied topically is actually absorbed systemically. Currently available TD systems (TDS) are either of the reservoir type or of the matrix dispersion type in which the drug is dispersed into a polymer matrix. Estradiol is the most appropriate steroid for TD and can be combined with progestins to ensure a contraceptive effect. The use of potent progestins allows effective plasma levels to be reached with low doses through application over a small area of skin. TDS changed weekly and delivering both estradiol and levonorgestrel at daily dosages of 38.4 and 28.8 mcg per 10 sq. cm daily, respectively, was found to suppress ovulation. ST 1435, a synthetic progestin derived from 19-norprogesterone, has also been shown to penetrate the skin when suspended in acetylated lanolin or dissolved in a hydroalcoholic gel and to suppress ovulation at a dose of 2 mg per day in a small number of cycles. TD systems should be perfectly adhesive, well-tolerated locally, and nearly 100% effective.
Databáze: OpenAIRE
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