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“We just heard a presentation about one of the several new devices for contraception and you took part in a lot of research about this Transdermal Patches for contraception.
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Hans van der Slikke, MD: “It’s October 2002 and we are in Seattle at the ASRM and next to me Professor Ronald Burkman. Very welcome.”
Ronald Burkman, MD: “Well, glad to be here.
Hans van der Slikke, MD: “We just heard a presentation about one of the several new devices for contraception and you took part in a lot of research about this Transdermal Patches for contraception. Can you tell me what’s the idea behind it? Why a patch for contraception?”
Ronald Burkman, MD: “Well, I think it is a very interesting concept. I mean, actually in the last few years we’ve got two sorts of brand new systems, in terms of delivery systems. The contraceptive patch, which is transdermal and also the vaginal ring, which is obviously trans-vaginal. The beauty of the system certainly the patch has been used in hormone replacement therapy, it’s been used for things like motion sickness, and for delivering drugs for angina, but it’s a steady release system and the hope behind it is you avoid a lot of the peaks and troughs that you get with an oral medication. And that hopefully you also reduce the overall frequency of side effects with continued use. What’s been noted with this particular system is that the ability of women to successfully use this, that is adhered to sort of the dosage schedule which is weekly for three straight weeks appears to be significantly better than, for example, their ability to use oral contraceptives. For a certain vulnerable population, such as adolescents and others, this in fact may reduce the unintended pregnancy rate which in the United States still is a significant problem, accounting for roughly 50% of the pregnancies we have each year.”
Hans van der Slikke, MD: “Yes. Basically a girl, woman takes it one patch each week for three weeks and then one week oppose?”
Ronald Burkman, MD: “Right. The way the patch is it mimics an oral contraceptive from that perspective. Again, it’s as you described, one patch weekly for three weeks and then there is the hormone-free interval. The patch is a matrix system. It’s 20 cm square, contains an outer layer that’s basically for protection. The inner or middle layer rather has the contraceptive steroids along with the glue and then there’s a peel-back layer for its application to the skin. It’s been tested in four different sites, the buttocks, the lower abdomen, the upper abdomen, obviously not the breasts, as well as the upper, outer arm and there is certainly bio-equivalents across all those sites. It delivers two hormones, one is Norelgestromin which is sort of the major metabolite of norgestimate progestin that’s probably used in the most widely prescribed OC in this country and also contains Ethinylestradiol which is the estrogen contained in, obviously oral contraceptives.”
Hans van der Slikke, MD: “What’s about the daily dose delivered?”
Ronald Burkman, MD: “The daily dose is about 20 micrograms of Ethinylestradiol and I think it’s 150 micrograms of Norelgestromin. Now a lot of people say, ‘Well then it’s really just a 20 microgram pill in a patch form’ but again, but remember this is sort of continuous release as opposed to the usual peaks and valleys that you would see with an oral dose. So direct comparability is really not possible.”
Hans van der Slikke, MD: “So but there is a…you can make a comparison. You can compare them as well in terms of safety?”
Ronald Burkman, MD: “If you look at the safety there are three large clinical trials involving several thousand women. Two were comparative with oral contraceptives and one was just sort of a use of the agent by itself. From the standpoint of efficacy the contraceptive failure rates are less than one pregnancy per 100 women a year and that’s for both typical use, which is sort of what, you know, is what reality is, as well as for method failure, that’s where they use it correctly. And in fact, the numbers were so close together it clearly would suggest that the women were adhering or complying with the correct use at a very high percentage of time. And in fact their self-report done has suggested over 90% correctly used it each cycle.”
Hans van der Slikke, MD: “Yes, and what about the side-effects because we know that patches, although they are much better than let’s say ten years ago, still can cause some, well maybe fall off, or can cause some irritation.”
Ronald Burkman, MD: “Well, for the patch itself, certainly from the standpoint of doing the clinical trials, having subjects sort of complain of, you know, some skin irritation that occurred in about 20% of subjects in the various clinical trials but only 2.5 % of women decided well this was to the extent that they didn’t want to continue. From the standpoint of adhesions there’s been over 70 000 cycles in the clinical trials and it looks like complete detachment occurs in about 1.8%, partial detachment in about 2.9%, something like that. Overall this does not appear to be affected by whether you’re in a cold climate or a hot, warm, humid climate. Also studies have been done evaluating women who exercise, use saunas, all that sort of thing and it appears that the patch adheres quite well. So overall I think certainly it does very well from that perspective.”
Hans van der Slikke, MD: “So, these are kind of heavy-duty patches?”
Ronald Burkman, MD: “Well, they’re heavy-duty in that they certainly deliver the goods so to speak in terms of contraceptive efficacy and the side effect profile is very similar to oral contraceptives but they actually are paper-thin. When you look at this it looks like well, this is like a band-aid you know one of those big square band-aids. But they are as thin as a piece of paper almost. And so they are kind of interesting from that perspective to think that you’ve got all this steroid in there that can deliver the levels that they do in something as small as that.”
Hans van der Slikke, MD: “And other side effects, like spotting, like breast tenderness?”
Ronald Burkman, MD: “Yes, the two side effects that, well, actually the one side effect that’s a little different is breast tenderness. This was seen in about 18-19% of women in the trials yet only 1% of women discontinued use because of breast tenderness. Furthermore, when you sort of exam the data a little more extensively you can see that most of the tenderness occurred only in the initial cycle and most women described the discomfort as being mild to moderate. Only about 14-15% felt that it was more significant than moderate tenderness. So it looks like it’s short-lived. After a couple of cycles the degree of tenderness is no different than say compared to OCs. Bleeding, break-through bleeding in the comparative trials was exactly the same between a, for example, a triphasic level Norgestrel oral contraceptive and the patch. There appears to be a little more spotting in the first cycle or so with the patch compared to the oral contraceptive but again that’s sort of short-lived.”
Hans van der Slikke, MD: “So women these days have a lot more choices for their device of contraception than ten or 20 years ago. For which part, for which woman this kind of transdermal patch is the most suitable?”
Ronald Burkman, MD: “You sort of look at this and say, ‘Well, this must be one of those sort of special sorts of methods of contraception’. Well, in reality if you make women aware of its availability you very quickly discover that a lot of the women, despite the birth control pill being out there for several decades now, really it’s difficult for many women to take this successfully, one pill each day without forgetting. In fact in this country, the United States, after five months of the patch being available, if the patch were an oral contraceptive it would be the second most commonly prescribed birth control pill in this country. So again, it certainly has taken off like crazy from the standpoint of women accepting it and finding it to be a method that they can use successfully. And I think the advantages, it’s weekly dosing. They can look on their arm, they can look at their abdomen, know that they haven’t forgotten anything. And it’s probably easier to do something on a Sunday once a week than it is to remember ‘Did I take that pill or not’ because again, you may not have any memory aids.”
Hans van der Slikke, MD: “Okay. I think you’ve convinced me that we have here a real good, new way for regulating the contraception. Thank you very much.”
Ronald Burkman, MD: “Well, my pleasure.”