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hormones, Uncategorized

Intravaginal DHEA isn’t an “alternative” to estrogen it’s the prodrug

Intravaginal DHEA (dehydroepiandrosterone) is being studied to treat atrophy the painful changes in the vaginal tissues that affect many women after menopause. It is being touted by the manufacturer and some doctors (especially those studying it and consulting for the company) as an alternative to estrogen. But is it?

First of all, atrophy is an important medical condition affecting over 50% of post menopausal women and about 1/3 of women who are peri menopausal. When I write these kinds of posts inevitably I get someone writing a comment that I want women to “suffer” by challenging the veracity of some drug company’s claims, so I’m going to remind everyone up front that critical appraisal doesn’t mean women should suck it up and have painful sex it means women should have the best care and get the facts. And since this often comes up just a reminder that I take no money from pharma.

The other important preamble is that there is already very effective therapy for this condition, intravaginal estrogen as well as the newer oral ospemifene (Osphena), although taking an oral medication to treat a vaginal problem doesn’t seem to appeal to many women especially as Ophena increases the risk of blood clots and women with a uterus will need to take progesterone to protect the lining of the uterus from the effects of the drug.

When you claim to have a new treatment it needs to be new and it needs to be at least as good as (if not better and as safe as if not safer) than what is available.  HOLD ONTO THIS THOUGHT.

What is DHEA?

Like estrogen it is a steroid hormone, meaning it is a derivative of cholesterol.  It is produced in the adrenal glands and to a lesser extend in the ovaries. The image below shows the relationship of the hormone DHEA (dehydroepiandrosterone) to cholesterol and estrone and estradiol (estrogens) and testosterone.

steroidogenesis

 

Yes, DHEA is converted by the body into androstendione and then estrone and estradiol. In fact, the newest study on the drug funded by the manufacturer that is getting lots of play in the press states:

DHEA provides estrogen and/or androgens only to the cells which possess the required enzymes to transform DHEA. 

The authors also sate that DHEA is “inactive by itself” so obviously it has to be the estrone/estradiol or testosterone that is improving things.

So yeah, DHEA isn’t an alternative to estrogen it’s a prodrug. It is made into estrogen by the body. Saying DHEA isn’t estrogen therapy which technically true, but I think is deceptive nonetheless.  It’s a bit like saying ice isn’t water.

 

 

Is it safer? 

The manufacturers claim that DHEA can only be converted to estrogen inside the cell. In the latest study they claim that serum estradiol levels remained “well within” the postmenopausal ranges. They do not provide the values, which is important as the levels can bump signifying some absorption and still be in the post menopausal range. This is of course what we see with low dose vaginal estrogen, the levels bump slightly but stay in the post menopausal range.  The current study provides no proof that anything different happens with DHEA. I am left to wonder if the estrogen levels do bump slightly, otherwise why not publish them?

So is DHEA safer than vaginal estrogen? There is no data to say that.

Is DHEA better than vaginal estrogen?

As they have only studied the drug against placebo there is no way to know. Studying your drug head to head with the gold standard is risky, because if it fails, well, your product is a bust.

 

So when you have a new treatment it needs to be “new.” DHEA isn’t. It is a new way to deliver estrogen, but that is way less headline generating.

Is it as good as or better than estrogen? No way to tell as it hasn’t been studied head to head.

DHEA also requires daily application per the few studies published and with vaginal estrogen most women can use 1-2 times a week or use a ring that doesn’t create any mess.

Prodrugs (medications that are converted into the active or desired form in the body) are often used in medicine. Sometimes they are truly better tolerated and sometimes it is a marketing ploy or a way to get around an expiring patent. Whether DHEA is better than estrogen or better tolerated or safer remains to be seen, but let’s not be dishonest and call it an alternative to estrogen.

 

 

 

Discussion

5 thoughts on “Intravaginal DHEA isn’t an “alternative” to estrogen it’s the prodrug

  1. As they have only studied the drug against placebo…

    It used to be the case that new drugs were tested against a ‘placebo’; I thought that today, best practice was to test a new drug against an equivalent, preferably a ‘gold standard’.

    Posted by korhomme | January 11, 2016, 2:57 pm
  2. Dr. Jen…keep writing these great web logs, please. What a treat to read your erudite, timely, swinging stuff. Your point-of-view is just and humane and carefully analytical. Thanks. Many many thanks.

    Posted by Jacqueline (Jackie) Levine | January 11, 2016, 7:57 pm
  3. Good one! And thanks for the refresher chart on steroid biosynthesis. I’ve kept a link to this blog post.

    Posted by joannevalentinesimson | January 12, 2016, 7:34 pm
  4. I’ve heard providers call it ” a precursor” to testosterone and recommend it orally (200mgi think ) to increase libido in women. Take it a few hours prior to sex. Any thoughts ?

    Posted by Cordtx | January 23, 2016, 9:27 am
  5. DHEA is a precursor, not a prodrug, in the narrower sense. But a real good article.

    Posted by GuThoma | February 10, 2016, 8:51 am

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