NEWS: new gel HRT; lower cardiovascular risks by using HRTs

The US FDA has just (this was first written in 2007) formally approved Divigel, a new 1% estradiol gel HRT. The product website is a horrific mess of a slow-loading flash file, but you can download the product prescribing information directly from the FDA as a pdf file.

It is intended for once-daily dose, applied to the thighs over a specific area (5"x7") and not safe to wash for at least an hour. The info states that steady hormonal levels are achieved by day 12 of dosing (although that doesn't necessarily mean that all other systemic accommodations have occurred—still, a useful bit of data). They note that delivered levels have not been evaluated with respect to sunscreen usage, although that is a known factor in altered delivery for gels. Its half-life is 10 hours, which is appropriate and typical for daily-dosed products (no, that doesn't mean you need to take a dose every 10 hours—if you're not clear on what "half life" means, we talk about that in our discussion of how to get an even hormone delivery).

As for the whole skin absorption and transfer thing, here's what it says in the prescribing leaflet:
Potential for Estradiol Transfer and Effects of Washing
As with most topical products, there is a potential for estradiol transfer following physical contact with Divigel application sites. The effect of estradiol transfer was evaluated in healthy postmenopausal women who topically applied 1.0 g of Divigel (single dose) on one thigh. One and 8 hours after gel application, they engaged in direct thigh- to- arm contact with a partner for 15 minutes. While some elevation of estradiol levels over baseline was seen in the male subjects, the degree of transferability in this study was inconclusive. 
The effect of application site washing on skin surface levels and serum concentrations of estradiol was determined in 16 healthy postmenopausal women after application of 1.0 g of Divigel to a 200 cm area on the thigh. Washing the application site with soap and water 1 hour after application removed all detectable amounts of estradiol from the surface of the skin, and resulted in a 30-38% decrease in the mean total 24-hour exposure to estradiol.
That's not much different from Estrogel or any other gel HRT, which may be part of why these deliver in such a different manner from creams and other transdermals.

The other interesting thing to be picked up here is that the original 12-week testing showed up a level of nasopharangeal (nose/sinus/ears/throat) effects and infections that might be some slight consolation to those women having these reactions to other HRTs and having hard going convincing doctors that these are hormone-related (this is quoting from the medscape summary linked above, but the data is also in tabular form in the product leaflet):
The most commonly reported adverse events associated with use of the 0.25-, 0.5-, and 1-g daily doses of the gel were nasopharyngitis (5.7%, 4.1%, and 4.8% vs placebo, 4.0%), upper respiratory tract infection (5.7%, 2.4%, and 1.6% vs 1.6%)
How does this compare with Estrogel, the other gel HRT available in the US? Primarily in terms of dose and strength provided; otherwise, pretty similar. Estrogel is covered on the Estrogen HRTs portion of this website; you can also find an entry for Divigel there.

For more on using gel hrts in general, see our new Troubleshooting gels article.

"A new analysis of the Women's Health Initiative (WHI) trial has found that younger postmenopausal women treated with estrogen-only hormone replacement therapy (HRT) had significantly less coronary artery calcification than their counterparts taking placebo" is what the coverage is headlined.

Citing a new analysis (which has actually been ongoing and we've seen some other recent announcements of more in-depth data evaluation from that study), the earlier question of estrogen HRTs causing cardiovascular disease and enhanced CV events is now showing results indicating that
While the results provide further reassurance to younger women that estrogen is unlikely to have an adverse effect on their risk of coronary events, "there is also a suggestion from the data that estrogen may slow the early stages of atherosclerosis"
"Younger" in this context goes all the way up to women in their 50s, distinguishing them from the 60s+ women who were in the studies.

While this new analysis indicates that women should begin HRTs at menopause to gain these protections, there is still quibbling over how long women should remain on them. The International Menopause Society in their 2007 guideline document is asserting that "women can be reassured that estrogen therapy is cardioprotective until at least 65." The chief of the National Heart, Lung, and Blood Institute WHI branch, however, weighs in that he prefers medical (drug) treatment of disease and is still concerned about the fact that initiating HRT at age 65 has negative CV impact—a fairly typically conservative illness-oriented medical approach.

That age of 65 may become the new sticking-point, just as the original WHI results that indicated that breast cancer risks rose to an arbitrarily-defined "too high" point after five years was popularly taken—and we mean by many doctors—as indicating that HRT was totally safe from day 1 to day 1825 and on day 1826 it became too dangerous to use. What this new analysis does is follow these women to age 65 without serious negative impact, but there simply is not yet enough data to allow them to project with absolute, demonstrated assurance that this safety continues. That is not at all the same things as data demonstrating that it does become dangerous immediately after one's 66th birthday (although don't be holding your breath that it won't be taken this way). Still, pushing back from five years from any age to age 65 is a major increase in rationality and a real boon for us in surgical meno. In fact, the Reuters article on this contains an interesting opposing quote:
Howard Hodis, a heart specialist at the University of Southern California, said there is "absolutely no evidence that if you start a women (on estrogen) at menopause at, say age 51, and continue that until she's 80, that her risk goes up as she gets older." 
The only important statistic, he said, is that continued estrogen therapy helps women live longer. 
"If you have a drug that reduces overall mortality, why wouldn't we use it? It's the best product for reducing bone loss," Hodis said.
So go, read those two articles—they provide considerable useful information on the rational use of HRTs and make major strides in undoing the damage the early sensationalist reporting of WHI caused. And for the sake of all menopausal women, do consider at least asking your doctors if they've seen these new study evaluations and offer to share the links with them if they haven't. The medscape article has been added to our bookmark account; the full study report is in the New England Journal of Medicine, Volume 356:2591-2602 - June 21, 2007 - Number 25, available only to subscribers.