ABSTRACT

Hormones like estrogen and progestin are widely used as contraceptive methods and for hormone replacement therapy (HRT) in order to reduce the symptoms of menopause prevent or treat osteoporosis and help reduce the risk of heart disease. Orally administered hormones have been prescribed for over 30 years. However, oral route presents several problems such as high first-pass hepatic metabolism and alteration of the metabolic system inducing changes in lipids, lipoproteins, carbohydrate metabolism, and certain haemostatic factors. In face of these facts, alternative administration routes have been studied to achieve effective blood levels, reducing daily doses and therefore side effects. Moreover, injectable, topical or transdermal dosage forms not only require a potent active ingredient for high efficacy but also effective drug delivery systems. In this context, the development of suitable drug delivery systems is necessary to provide single daily application, make prolonged use possible, improves the patient compliance with the therapy and reduce side effects. Transdermal delivery systems for HRT are already marketed (Estraderm^®), which maintain relatively constant drug level within the circulation, allow lower drug dose, reduce frequency of drug dosing, and are easy removed to interrupt the therapy. Until recently, no alternative combination hormonal products were available to women other than combination oral contraceptives. However, recent developments include delivery systems that are more convenient to the user, with the hope of decreasing contraceptive failures associated with incorrect use. New options include the combination estrogen-progestin monthly injectable (Lunelle™), the levonorgestrel intrauterine system (Mirena^®), the combination estrogen-progestin vaginal ring (NuvaRing^®), and a combination estrogen-progestin transdermal contraceptive (Ortho Evra/Evra™). Other options of delivery systems in market or under development for steroids include: (i) subdermal implant systems (Norplant^®) which were shown to provide a sustained release of low levels of hormones that are maintained for about 60 days; (ii) nasal spray (Aerodiol^®), a new estrogen therapy that led to a pulse-like estrogen profile; (iii) microparticulate systems aerosolized into lungs which were demonstrated to elevated systemic concentration for 5 days depending on the diameter of the particle porous; (iv) microparticles for intramuscular administration, which provided a sustained delivery up to five months and (v) systems for intravaginal delivery of hormones, such as estradiol ring (Estring^®) and estriol cream (Synapause^®) used for treating urogenital symptoms of menopause. Therefore, the aim of this review is to highlight recent progress on the developed and improved technologies for estrogen and progestin administration, as well as to present ways holding promise for the improvement of HRT and contraception.