EXPERT REACTION: New long-acting contraceptive delivers hormone via microneedle patch

More than 50% of spontaneous pregnancies in Australia are unplanned. So many in fact, that doctor groups like the AMA frequently call for pregnancy to treated as “an accident” in private insurance policies and offer cover in all policies, rather than having pregnancy excluded from all but top-level insurance policies.

Apart from social, economic and emotional upheaval, unwanted pregnancies can result in women needing termination of pregnancy which according to provider statistics (Children by Choice) run at 15-20 per 1000 Australian women, and is considered high by international standards.

Prevention of an unwanted pregnancy is the very much preferred alternative and novel safe, effective and easy to use methods of contraception are always welcomed. Compared to other nations, Australia has an increased reliance on oral contraceptives (and barrier methods like condoms), which although effective if used correctly, can cause side effects, inconvenience and require women to be compliant with their daily administration.

The World Health Organisation (WHO)  is on the record as saying Australian women should be using more Long-Acting Reversible Contraceptives (LARC’s) like implants, injections or intrauterine devices, which are associated with fewer method failures from compliance and result in less unwanted pregnancy. 

This study looks at a promising new drug delivery system for a progesterone-only contraceptive which has significant implications for a whole range of other drugs.

Progesterone-only contraceptives have advantages for some women, especially those needing to avoid added oestrogen. In addition, non-oral administration of the hormone can also provide specific benefits in some women.

The “effervescent microneedle patch” technology described in this research, is a special delivery system whereby microneedles containing Levonorgestrel (an artificial progesterone hormone already in use as a contraceptive) are embedded in a small skin patch which is applied by the woman to her skin.

After 50 seconds, a chemical reaction causes the microneedles to be released from the patch and painlessly insert into the skin where they start slowly dissolving and release the active ingredient. The patch can then be discarded and not does contain any sharps or biologically active agents, dispensing with the need for specific biological waste containers.

Animal and human recipients were studied and no significant adverse effects were reported. Skin redness usually disappeared within an hour and pain, if present at all, was much less than that experienced with an injection.

Patient acceptability across multiple continents was high and women reported liking the idea of self-administration of LARC’s without need for doctor visits, invasive injections, implants or IUD insertions. A number reported a preference for longer acting (3- or 6-month patches) and this needs further study as does contraceptive efficacy and cost.

Transdermal delivery of drugs is a rapidly growing area and the use of microneedle technology rather than traditional adhesive based patches offers a number of advantages especially in hot and humid countries like ours where patches can slip or fall off and adhesives can irritate.

If successful, this delivery system can be expanded for many more drugs (not just hormones) and is certainly worthy of further development.

This study describes a novel approach to administering a contraceptive agent via a one-minute application of a skin patch. The authors used Levonogestrel for this study as the active agent responsible for the contraceptive effect. This is the same compound that is used in some oral contraceptive pills, implants, patches and intrauterine devices such as Mirena.

As stated by the authors, Levonorgestrel has been used in various preparations for contraception for a number of years since the 1960s, has an excellent safety record and well-studied profile.

The current study combined a number of research projects which included testing the contraceptive patch on mice, testing placebo patches on human volunteers, and interviews with women regarding acceptability and desirability of yet another contraceptive option. The proposed application of the microneedle patch technology described in the article would consist of a one-minute contact of the patch with the skin, applying some pressure on the patch. In that time microneedles containing Levonorgestrel will be deployed under the skin. These microneedles will slowly be absorbed by the women’s bodies, and due to its gradual absorption, Levonorgestrel will slowly be released into the bloodstream over a period of time (authors studied monthly patches). The advantages of this contraceptive method are the ease of self-administration, safety and effectiveness, possible low cost and full reversibility.

It must be pointed out that the authors did not invent a new contraceptive drug, but rather used a very old one in a novel application device. While Levonorgestrel has a very good safety and effectiveness record, it has certain side-effects that are also well recognised and which are likely to be unaffected by the new administration process. Two of the most bothersome side-effects of Levonorgestrel-containing long term contraceptives are irregular bleeding and undesired psychological effects. These are not addressed by the paper. 

This study can only be considered an initial step in developing a novel option to administer Levonogestrel for contraceptive purposes. The active patch was not administered to human participants, who were only tested with placebo patches. The pharmacological profile of the device was only tested in mice and may not to be completely translatable to humans.

Interviews with women regarding acceptability and desirability of such contraceptive patch being available did not include questions on costs and possible side-effects. Further research is clearly required in order to ensure that this patch microneedle technology is safe and effective in humans. One must also be mindful of further significant research effort that is required to gain regulatory approval in various countries such as FDA in the USA and TGA in Australia, I would anticipate that it will be between five and seven years before the patch is available to be used by the general public.

Microneedle patches are an exciting and promising way of improving access to common and important medications that are usually administered by needle or tablet. 

Microneedle patches have promising benefits over traditional methods of administration: they are very simple and safe to administer and self-administration may be possible, with simple instructions. They are likely to be cost-effective if they remove the need for expensive medical procedures. 

In this study we see the potential of a microneedle patch for long-acting reversible contraception. The authors show data in rats that the microneedle patch maintained protective levels of a common and highly effective contraceptive for more than a month. They also showed that the mechanism of the dissolving microneedle patch also worked in human skin. They also showed that a small sample of women indicated that they would prefer to use contraception administered by microneedle patch than by needle or by daily tablet.

If this technology is shown to work in humans, it has the potential to improve access to effective contraception, due to the simplicity of use. This is especially important for young women and women in low-income countries where cost and access to services are challenges to contraception access.