Gleanings from an article on contraceptive patches

Since we're always interested in expanding our understanding of patches and transdermal hormone delivery, we recently clicked through on "Transdermal Contraceptive Patches: Current Status and Future Potential" (free signup required to read) just to see if it had anything to offer that also seemed applicable to hrts. As it turned out, that was a good move.

Delivery from alternative patch placement locations

We've known for some time that butt and belly application differs by 17-25% in the amount of hormones absorbed from the same patch because it's in the patch data sheets. Women have variously reported using upper arm and upper back and thighs for patch placement for years, but we're never had any guide other than experimentation to determine the correct dose equivalency for those locations. This current article, however, lists some of these locations and reports on their delivery:
The patch is designed to be placed on one of four sites: the lower abdomen, upper arm, buttock or upper torso (excluding on the breasts). Two consecutive patches should not be placed over the exact same area. Hormonal absorption from the lower abdomen is approximately 20% lower than that observed from the other three sites
There's no reason at all to suppose that this would not hold true for hrt-sized doses as it does for the higher contraceptive-sized doses referenced in the article. That means that we don't especially need to anticipate making huge changes to our patch dose if we choose to spread use out over more alternative locations.

What's underneath still matters

This doesn't, of course, guarantee that even the sites with roughly the same statistical deliverability can be trusted to work that way on an individual basis--we still have to contend with individuality of fat-vs-muscle underlayment of the skin to which the patch is applied. That's also supported by this statement from the article:
cautioned that women with body weight in excess of 90 kg may be at higher risk for pregnancy compared with lighter women
In other words, women with a larger fat layer the hormone must traverse to enter circulation may have an overall lower delivery. For well-padded women, then, a patch may not be an optimal delivery if transmission through thicker fat layers prevents good uptake. Beyond this, though, it supports the notion that underlaying tissue type is pertinent to patch delivery for all women, something that may help in troubleshooting variations in patch performance that result from using multiple locations.

Environmental impact of patch disposal

Also of general interest is this reminder of the environmental impact of undelivered hormones:
As there is still a considerable amount of hormone left in the patch at the end of its 7-day use, it is recommended that patches not be flushed down toilets, but disposed of folded in half via solid waste collection systems. In some countries, it is recommended that the used patches are returned to pharmacies.
While women in menopause tend to come closer to exhausting the hormone content of their much lower dose patches by the end of the nominal delivery life, we should keep in mind that there may still be enough in them to have impact on others. Our water supplies are growing increasingly contaminated by hormones and drugs, none of which are typically measured (in the US) by EPA-mandated water supply testing. This contamination is increasingly pointed to as a potential factor in the earlier sexual maturity of girls and the higher incidence of hormone-mediated disorders we women suffer.

We might be especially concerned about patches discarded prematurely--say, that one that got caught on our underwear on day 1 and peeled up and had to be replaced. But any patch, really, should be disposed of with some care as to where its leftover content might end up, given that it's unfilterable and untested once in our water supplies. Even their suggestion that it go into solid waste disposal would be ineffective in safely sequestering it some places, such as New York City, where much solid waste is simply barged out to sea and dumped. Responsible disposal of our hrts is something to think about for the sake of our daughters and granddaughters.

Transdermal delivery and the risk of blood clots

The main issue that this article is addressing is risks of blood clots. In general, we know from a growing body of evidence that oral hrts (as compared to transdermal) seem to be associated with a higher incidence of clots, generally attributed to the way that the liver is more heavily involved in oral dose processing. The article reviews that situation:
Estrogen increases VTE risks by altering hepatic production of extrinsic clotting factors, and antithrombin III. With oral contraceptives, hepatic exposure to estrogen is much higher than is reflected by serum estrogen measurements. This is because much of the estrogen absorbed through the intestine into the liver is conjugated and excreted through the gallbladder back into the intestine without ever entering the bloodstream. However, with transdermal systems, all the estrogen to which the liver may be exposed is reflected in the serum levels.
Oral processing is also generally believed to boost inflammatory factors (such as C-reactive protein), which has been suggested as a reason why cancer rates may be higher with orals than other delivery. This is also considered to be a factor in the cardiovascular disease development issue as it relates to route. This research is not yet heavily publicized even though it's incorporated into the major medical group consensus documents on menopause and hrt, so many physicians remain unaware that these are reasons for women to downrate oral hrts when they are evaluating their options.

Transdermal progestins?

We've been discussing progestins more lately, both with women who have endometriosis and want to include the suppressive effects of progestogens (progesterone-acting compounds) in their hrt, and with women who have had their ovaries removed but still have an intact uterus and a need to utilize a progestogen to maintain its health.

There's some evidence that progestogens that deliver into pelvic circulation provide better local coverage with lower systemic impact as compared to other routes of systemic delivery, something very attractive where the alternative has long been simply having to tolerate an unpleasant hormone imbalance for the sake of therapeutic effect.

To date, local progestogen delivery has been possible only via IUDs such as Mirena ( dispensing the progestin levonorgestrel) or other higher-dose progestin-dispensing contraceptive IUDs (like Progestasert), or vaginal forms such as the progesterone gel Prochieve, off-label use of oral Prometrium caps vaginally, or various vaginal-application compounded forms of progesterone. That means that for women who want the stability of a progestin, which cannot be converted to other hormones as progesterone itself can be, if they didn't have a uterus they were out of luck for anything other than oral delivery and its associated systemic impact.

But this article supports the premise that progestins are in fact capable of being absorbed through the skin (and, by extension because they have similar properties, vaginal lining). Gestodene is the progestin mentioned as being possibly suitable for this kind of delivery in this article and norelgestromin is the progestin in the currently-available patch, but the article also suggests that "other progestins, including those with poor oral absorption, could be utilized in a transdermal patch."

While that doesn't mean that anyone's going to rush a vaginal or transdermal progestin onto the market, especially one suited for the use of women in surgical menopause, it does open up some other avenues for the adventurous to explore.

How? Vaginal use of a portion of a plain progestin tablet meant for oral use might work (it would obviously make sense to try one of the progestins the article mentions unless one can get solid information from a pharmacist that a different progestin is known to be suitable in terms of through-skin absorption capability). Why only a portion? Remember: oral formulations have a lot of wastage from first pass built into them, while lower losses with transdermal delivery mean we have to start at a lower dose level. Clearly, this is really out-on-the-edge experimentation and definitely something to discuss with one's health professionals, but it does provide the hint of a possibility for women willing to experiment a bit in order to get an hrt form and dose they are more comfortable with.

Another approach, although we're not sure if it's feasible or not, would be to see if a compounding pharmacy could custom formulate a progestin meant for oral use into a vaginal-suitable dose and vehicle. We've hesitated suggesting this in the past because we had no reason to suppose it would be absorbed, but given the encouragement of this article, it sounds much more like something to pursue.

Have you tried this? Thinking about trying it? We'd love to hear from you about your experiences on our discussion forum.