Despite the number of oral contraceptive options on the market, there is still a pressing need for estrogen-free oral contraception in order to reduce the risk of venous thromboembolism (VTE), particularly for obese women, and to provide contraception for women with other medical contraindications to estrogen. The only approved oral estrogen-free hormonal contraceptive method is the progestin-only pill, which has a number of drawbacks, including strict adherence to dosing at the same time every day and possible bleeding irregularities. In contrast, daily low dose oral progesterone receptor modulators, such as ulipristal acetate, have been shown to inhibit ovulation and induce amenorrhea very early in the course of the treatment. Furthermore, selective progesterone receptor modulator treatment is associated with physiologic levels of endogenous estrogen. Taken together, these features support the working hypothesis that an oral ulipristal acetate contraceptive regimen would open a new path in the management of regular contraception.
To provide preliminary evidence that daily, low dose ulipristal acetate could be safe and effective for contraception, a phase II clinical trial is ongoing under the auspices of the NICHD Contraceptive Clinical Trials Network.
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Donnez, J., et al. (2012). “Ulipristal acetate versus placebo for fibroid treatment before surgery.” N Engl J Med 366(5): 409-420.
Donnez,J., et al. (2012). “Ulipristal acetate versus leuprolide acetate for uterine fibroids. ” N Engl J Med 366(5) : 421-432.
Intrauterine devices and systems (IUD/IUS) represent the most cost-effective reversible method of contraception available to date, due to their high effectiveness and long duration of action. There are currently two major categories of IUDs:
• The copper IUD, which acts as a spermicide that inhibits sperm motility and viability within the uterus. One of the most advantageous effects is that copper IUD works immediately upon insertion and fertility returns quickly upon removal. In addition, the lifespan of a copper IUD ranges from about 2 to 12 years, making it a very long-acting method of birth control and one of the most effective methods of contraception with no compliance issues.
• The hormonal IUS, which has a plastic frame containing and releasing a progestin, most commonly levonorgestrel. A small amount of hormone is continuously released into the uterus, thickening cervical mucus and blocking spermatozoids movement, so it cannot enter the cervix and reach the egg. Current hormonal IUS may be effective for up to five years.
A selective progesterone receptor modulator, such as ulipristal acetate in an IUD holds the potential to provide an innovative alternative to the current systems. HRA Pharma is therefore developing a pre-clinical prototype capable of releasing ulipristal acetate at a controlled continuous rate.
Compliance with daily administration of a contraceptive pill remains one of the biggest challenges in the contraceptive field. There is therefore a need for long-release formulations of a contraceptive agent. In collaboration with the Population Council, a leader in the development of innovative contraceptive technologies, HRA Pharma is developing a contraceptive vaginal ring containing ulipristal acetate, a progesterone receptor modulator. Such locally delivered, slow-release, non-estrogenic hormones would enable effective cycle control.
Phase II clinical trials were started after confirming that ulipristal acetate can be contraceptively effective, when vaginally administered via a sustained-release formulation.