Today, we’re going to dig into an adrenal hormone called DHEA (dehydroepiandrosterone), courtesy of this question I received from a blog reader via email:
“Over a year ago I went to a gynecologist with the suspicion I had high testosterone levels and maybe have PCOS. Weirdly, my testosterone levels are normal but the gynecologist was alarmed by my high DHEA levels and told me to find an endocrinologist as soon as possible.
After a year or so of trying to get a referral that was accepted by Medicare (no easy feat), I have seen an endocrinologist three times and have gotten my blood tested with the same results: high DHEA levels. He is concerned but only enough to say that my levels need to be monitored for several months before we make any kind of decisions as far as medicine or whatever.
As an average person is inclined to do, I’ve done a fair bit of reading online (ugh) and 90% of what I’ve seen seems to relate to adrenal fatigue and other flaky sounding faux diagnostics. I’m super confused, my doctor doesn’t have great bedside manner, and I would love to hear from someone who might be inclined to write a rational and educated blog post explaining DHEA and what “woo-woo” ideas are out there and how to avoid them.”
Jennifer’s (not her real name) question is a good one, as there is a hefty dose of nonsense out there when it comes to the discussion of DHEA. As a general rule:
If your doctor/provider is ordering a DHEA level because she thinks it may be high, that’s usually appropriate. If your provider is ordering it because she thinks it might be low, you are probably wandering into Quackery territory. Finally, if your provider is ordering it “just because,” then you need to run – not walk – out of that office and head for the hills.
To understand why your doctor might want to look for a high DHEA level, I need to do a brief review (warning: this gets boring for a few sentences) of what the heck DHEA is, just so we’re all on the same page. It is one of the most abundant (but weak!) circulating androgenic (masculinizing) hormones in premenopausal women. Importantly, DHEA levels have a diurnal variation (they are higher in the morning), whereas DHEA-S[ulfate] levels are stable throughout the day. Because DHEA-S levels are stable and present at a higher concentration than DHEA levels, DHEA-S is what we measure in patients. So if you see DHEA on your lab results instead of DHEA-S, that’s a red flag that your provider may not know what she’s doing.
DHEA-S is produced de novo only by your adrenal glands, and it then gets converted to stronger, more active androgens, like androstenedione, androstenediol, testosterone, and 5-dihydrotestosterone (5-DHT). Testosterone and 5-DHT are the hormones primarily responsible for androgenic effects (they are the hormones that actually bind to the androgen receptor).
When it comes to androgenic effects, most women are not concerned with all the good stuff that androgens do; rather, the reason why they seek help from the doctor is because of the bad stuff that excess androgens do to females. Mainly, we’re talking about acne; dark, coarse hairs on the face and body; loss of hair from the head; and irregular periods.
When a woman presents to her doctor with signs of androgen excess, it’s quite reasonable to check one or more of the above androgenic hormones, to see if there is obvious over-production. There isn’t universal agreement on exactly how much money to spend on lab testing, but it’s fairly common to check at least testosterone +/- DHEA-S. For various reasons – some of which involve the idiosyncrasies of different testosterone assays out there – one or more of the measured androgens may be high, while others may be normal (i.e. Jennifer’s DHEA-S could be elevated and the testosterone normal, as she suggested).
The vast majority of adolescents and young women with elevated levels of one or more androgens will ultimately be diagnosed with PCOS (polycystic ovarian syndrome). A detailed discussion of PCOS is outside the scope of this piece; it deserves a dedicated post.
A source of confusion for women (and sometimes their doctors) is when androgen levels are elevated and the diagnosis isn’t PCOS. What else could it be? As I’ve stated before, this blog is not a “medical-o-pedia” site, but I’m always happy to link out to good sources of information. If you’re really interested in delving into the detailed differential diagnosis, you can check out the Endocrine Society’s guidelines for diagnosing and managing hirsutism in premenopausal women. You’ll notice that the ES’s guideline paper does not go into detail about every possible diagnosis they list in the differential, but if you want to know more about a particular diagnosis, chances are the ES has published a guideline about just that topic on their website. If you happen to be a postmenopausal woman, I don’t want you to feel left out, so you can also get as deep into the weeds as you like by reading Hyperandrogenism after Menopause.
To summarize, most cases of modestly elevated androgen levels in premenopausal women represent PCOS. When it’s not PCOS, there’s a relatively short list of other things your endocrinologist should consider. Now, when the androgen levels get really high, the first thing most patients want to know is, “Is it cancer?!” To address that, we have to define “really high.” Unfortunately, there isn’t universal consensus, because plenty of women have high numbers without invoking a malignant process. As a general rule, though, we try to rule out the presence of an ovarian tumor when the testosterone is above 150-200 ng/dL (5.2-6.9 nmol/L); we look for an adrenal tumor when the DHEA-S is above 600-700 mcg/dL (16.3 – 19 μmol/L).
Now that we’ve covered the aspects of androgen measurement that are evidence-based, let’s turn our attention to the aspects of DHEA that stray into the realm of quackery. Earlier, I gave you the rule of thumb that, if your doctor is looking for high levels, that tends to be kosher. Let’s talk about the (usually) non-kosher search for low levels.
Naturopaths and other non-evidence-based practitioners may check blood and salivary levels of DHEA, DHEA-S, and other adrenal hormones as part of a workup for “adrenal fatigue.” Unfortunately, they are attempting to diagnose a condition that does not exist. If you haven’t already, now would be a great time to read one of my prior posts, Adrenal Fatigue – A Fraud Perpetrated On Unsuspecting Patients.
This is a fairly simple concept. Adrenal fatigue ≠ exist. Do not be fooled by your naturopath with variations on the theme of adrenal burnout:
- We just need to support your adrenals.
- Your hormones are just a little out of balance, but we can restore that balance.
- Yes, your numbers are normal, but in my experience, most women do better with high-normal levels.
Now that we’ve gotten that out of the way, the broader question is, “Is there an actual androgen deficiency syndrome in women?” According to the best available evidence, there is no reliable way to make that diagnosis in women who are otherwise healthy. However, there are a few situations in which women could potentially suffer from androgen deficiency and might benefit from treatment:
- Women who have had both ovaries removed have lower testosterone levels than women who go through a natural menopause, as the postmenopausal ovary continues to make testosterone.
- Women with primary adrenal insufficiency (Addison’s disease or adrenal failure of other causes) obviously won’t make as much adrenal androgen.
- Women with pituitary failure (hypopituitarism), particularly pituitary glands that are no longer making ACTH or gonadotropins (the hormones that stimulate the adrenals and ovaries, respectively) may have lower androgen levels.
If you really want to dig into the details of androgen therapy for women, you can do that here. This is a simplified version, based on the evidence:
- There is no clear correlation of blood androgen levels with symptoms like decreased sexual desire or general well-being. Therefore, looking for low levels of androgens is usually going to be a fool’s errand.
- There is no good evidence that routinely treating low levels of androgens with T (testosterone) or DHEA leads to an improvement of symptoms.
- There is no good long-term safety data regarding the use of T or DHEA for women.
- The best evidence for benefit from T therapy is in postmenopausal women with hypoactive sexual desire disorder.
The Role for Androgen Therapy in Evidence-Based Endocrinology
In Endocrinology, we traffic in quantifiable hormones that have measurable effects on the body. We love to look at numbers and symptoms, track them, and optimize them. So what do we do when that’s not possible? This is where the art of medicine comes into play. Unfortunately, when the evidence base is thin (or when the evidence clearly shows that a treatment is likely to be ineffective), this provides a hole that naturopaths and other fringe practitioners are eager to fill. This results in women getting loaded up with hormonal pills, drops, and creams – some will be ineffective, and some will be harmful.
In my practice, I do not routinely search for low androgen levels in women with nonspecific symptoms of fatigue, decreased libido, etc. However, in women with true adrenal failure or hypopituitarism who have mood or libido symptoms, I will sometimes empirically try 25-50mg of DHEA. I honestly haven’t used it often enough to form an opinion of whether it works. Anecdotally, I can say that the women in whom I’ve tried it have felt no better.
In postmenopausal women with sexual dysfunction/low desire, I have rarely prescribed a compounded testosterone cream, starting with 300-400 mcg to the skin once daily. Ordinarily, “compounding” is a dirty word in Endocrinology, as it is associated with compounding pharmacies, which have no external oversight and tend to do some quacky things. But, since there is no FDA-approved formulation of testosterone for women, I use the compounding pharmacy. I have seen clinical improvement in a couple of women over the years, but I admit that I haven’t used it often enough to have an informed opinion.
In the above examples, I monitor DHEA-S and testosterone levels, respectively, to make sure I’m not giving the woman too much. I will boost the dose until we either see symptom relief, side effects, and/or levels that are too high. If we boost the dose to achieve a robust blood level and there is no clinical improvement within a few months, then we stop therapy.
The Bottom Line
Looking for high levels of androgens in women who present with signs of male hormone excess is reasonable. Searching for low levels of androgens in otherwise healthy women with nonspecific symptoms is not recommended. Treating these healthy women with a cocktail of androgenic hormones and passing it off as balancing their hormones is quackery, pure and simple.
Have you had androgen testing? Have you ever been told your levels are high? Low? What type of treatment did you have, and did it work? If you’re a doctor, how do you handle healthy patients who request this type of testing?
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