Supplements, Part I: DHEA

As I mentioned in my last post, our game plan is to proceed with the “soft science” in an effort to improve my egg quality before trying IVF again. Dr. Y (and I) refer to this as soft science because there is so little evidence that it works. But, since there isn’t any “hard science” to suggest how I might improve my egg quality, the soft stuff is all I have available to me! And the specific weapons in my soft science arsenal include acupuncture and dietary supplements.

Here are the supplements I’m taking (in my fancy new pill organizer – it’s a bit unnatural how fond I am of it…see, you push down the little colored tab, and the compartment pops open with a satisfying ‘click’…)

Image

By name, here’s what I’m taking:

  • aspirin (81 mg, 1X per day)
  • coenzyme Q10 (400 mg, 3X per day)
  • DHEA, micronized (25 mg, 3X per day)
  • fish oil (1000 mg, 1X per day)
  • L-arginine (1000 mg, 1X per day)
  • melatonin (3 mg, at bedtime)
  • myo-inositol (2 gm, 2X per day)
  • prenatal vitamin (2X per day)
  • pycnogenol (30 mg, 3X per day)
  • vitamin C (500 mg, in the morning)
  • vitamin E (200 IU, 1X per day)

As you can see, it’s a long list, so I’ll break it down into a few posts. Today I’ll start with DHEA, perhaps the most widely-prescribed supplement for DOR-sufferers like me (albeit with scanty scientific evidence to support it…) Here’s what I think I know about DHEA, but first:

I am NOT an endocrinologist, or any kind of medical professional! This blog does NOT purport to offer medical advice, medical opinions, or recommendations. Please take this for what it is – the ramblings of an infertile woman trying to make sense of her diagnosis and treatment!

*****

DHEA is short for dehydroepiandrosterone, a “male” steroid sex hormone (or androgen) that serves as a precursor to testosterone (and estradiol for that matter). I wrote previously about the theory behind using androgens to treat female infertility. In brief, DHEA produced in the adrenal glands and ovaries gets converted to testosterone in the ovarian theca cells. This testosterone travels to the ovarian granulosa cells, where it is converted to estradiol. In addition to making estradiol, the granulosa cells surround the egg and are responsible for producing additional hormones to stimulate egg growth. Androgen levels (including DHEA and testosterone) tend to decline with age, and some researchers think that diminished ovarian reserve is a condition characterized by low androgen levels. In theory, adding extra DHEA through supplementation will stimulate the granulosa cells, leading to an increase in follicle growth and responsiveness.

Image

In the US, DHEA is easily available over the counter, and a large number of DOR women are currently taking DHEA with the hopes of improving their ovarian responsiveness. However, the verdict is still out on whether this works at all. From what I can tell, DHEA’s biggest proponents are Drs. Norbert Gleicher and David Barad of the Center for Human Reproduction. Here’s a summary of their research articles and a snazzy video. At the other end of the spectrum, Dr. Geoffrey Sher of the Sher Institutes for Reproductive Medicine is convinced that DHEA supplementation for DOR patients is a bad idea, a stance which he articulates in his popular blog.

To try and get to the bottom of the DHEA debate, I once again enlisted the help of PubMed, a database of citations from the biomedical literature.

First, I searched for “diminished ovarian reserve DHEA”. This search yielded 20 hits, of which 13 concluded that DHEA improves pregnancy rates in DOR patients, and 7 articles concluded there is not enough evidence to indicate a beneficial effect of DHEA supplementation.

At a first glance, this would seem to strongly support using DHEA – 13:7 in favor of DHEA, and the 7 detractors are saying there is no effect, not that there was an adverse effect of DHEA supplementation. But on closer inspection, I noticed that 11 of the 13 pro-DHEA articles came out of a single research team. Many of these articles were case studies. None were the sort of double-blind placebo-controlled studies that satisfy me as a scientist. (Although, in their defense, I found hardly any infertility studies that would qualify as double-blind placebo-controlled studies…Reproductive endocrinology in practice just doesn’t seem to be very evidence-based…)

So, who is this prolific, pro-DHEA research team? They are none other than Norbert Gleicher and David Barad of the Center for Human Reproduction. Now, the fact that they publish a lot about DHEA is certainly not a reason in itself to be suspicious of their conclusions. However, I did find the following disclosure (included in the text of one of their articles) worth considering:

“N.G. and D.H.B. are listed as co-inventors on two, already granted US user patents, which claim therapeutic benefits from DHEA supplementation in women with DFOR and DOR: both authors are also listed on additional pending patents in regard to DHEA supplementation and on pending patents.”

So they clearly have a financial interest in the efficacy of DHEA. I also think it’s worth mentioning that the SART stats for the clinic Dr. Gleicher heads (listed as American Infertility of New York PC on the SART database), are underwhelming…even when I sort the data to view only the stats for couples diagnosed with diminished ovarian reserve. Of course, stats aren’t everything; there are a number of reasons why their clinic might have lower stats (for example, if they take the cases that everybody else won’t, etc.) Still, I’m inclined to take their research conclusions with a grain of salt.

Here are some selected quotes from articles about DHEA:

from articles in favor of DHEA supplementation for poor responders from articles showing no benefit to DHEA supplementation
  • “several studies have suggested an improvement in pregnancy rates…While the role of DHEA is intriguing, evidence-based recommendations are lacking…large randomized prospective trials are sorely needed. Until (and if) such trials are conducted, DHEA may be of benefit in suitable, well informed, and consented women with diminished ovarian reserve.”
  • “DHEA supplementation is an effective option for patients with DOR.”
  • “Although more data on the dehydroepiandrosterone effect on assisted reproduction are needed, results obtained over the last few years confirm the improvement of oocyte production and pregnancy rates. No significant side effects are reported, and those include mainly hirsutism and acne.”
  • “DHEA does not appear to exert influence via recruitment of pre-antral or very small antral follicles (no change in AMH and inhibin B) but rather by rescue from atresia of small antral follicles (increased AFC).”
  • “The improvement of reproductive parameters after DHEA supplementation in poor responders may be explained through the effect that this pro-hormone exerts on follicular microenvironment.”
  • “Dehydroepiandrosterone supplementation can have a beneficial effect on ovarian reserves for poor-responder patients on IVF treatment.”
  • “no significant difference in the clinical pregnancy rate and miscarriage rates…insufficient data to support a beneficial role of DHEA”
  • “low DHEA levels do not suggest that supplementation with DHEA would improve response or pregnancy rate.”
  • “Although androgens may be biologically plausible, current evidence is not sufficient to prove their effectiveness…patients should be counseled regarding the experimental nature of such a treatment.”
  • “We believe that large-scale, well-designed confirmatory studies are necessary to prove the efficacy of DHEA before it can be recommended for routine use.”
  • “Based on the limited available evidence, transdermal testosterone pretreatment seems to increase clinical pregnancy and live birth rates in poor responders undergoing ovarian stimulation for IVF. There is insufficient data to support a beneficial role of rLH, hCG, DHEA or letrozole administration in the probability of pregnancy in poor responders undergoing ovarian stimulation for IVF.”
  • “There is currently insufficient evidence from the few randomized controlled trials to support the use of androgen supplementation or modulation to improve live birth outcome in poor responders undergoing IVF/ICSI treatment.”

What did I conclude from all this?

  • Dr. Y was right not to prescribe DHEA off the bat. Now I’m not a physician, but if I were, the amount of evidence out there about DHEA and DOR is insufficient for me to justify encouraging patients to pump themselves full of expensive performance-enhancing steroids. (Yes, DHEA is on the WADA List of Prohibited Substances. I’ll write more on the overlap between this list and most IF treatments in a future post…)
  • Aside from acne and hair growth, DHEA probably won’t hurt me. Dr. Sher’s objections notwithstanding, I can’t find any evidence to show that DHEA supplementation (at a dose of 50-75 mg/day) is likely to be harmful. Even Dr. Sher’s blog didn’t give any particular reason why he thinks DHEA is harmful, or any published studies showing that it is. Publishing an opinion on a blog is just that – an opinion. I certainly don’t lend it the same level of credibility as an article published in a peer-reviewed scientific journal. (Unless it’s my opinion on my blog; in that case, you should take it as Gospel!)
  • I’m ready to try DHEA. While I think it was the right decision not to take DHEA prior to my first IVF cycle, now we have more information. From my failed cycle, we know that I’m a poor responder (even on the protocol specifically designed for poor responders), and that my egg quality is crap. The properly randomized and placebo-controlled “good science” has failed me, and all that’s left is this “soft science”.

I think it’s significant that several of the studies I found specifically suggested that physicians should only prescribe DHEA to “well-informed” and consenting women who fully appreciate its experimental nature. I think now I can safely say that I fall into that group…

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43 Comments

  1. After testing my testosterone (it being low), I agreed to DHEA 75mg a day. I think the only side effect I’ve experienced is the pimples on my neck and chest area. Good thing they are not growing on my face. I’m also on three other things that were prescribed by my RE. One of them being melatonin. 3mg totally knocked me out. So we tried 1mg then moved on to 2mg. Now 2 is my dosage as 3mg still made me drowsy when I woke up in the morning.

    Reply
    • Interesting about the melatonin! I totally get sleepy about 30 minutes after taking it, but C doesn’t believe me; he thinks it’s psychosomatic! Fortunately, the grogginess doesn’t carry over to morning though. What are the other two things you’re taking?

      Reply
      • I’m also taking this thing called “Total Fertility” that my RE believes gives you a bunch of strong antioxidant that you need, which includes DHA/EPA, antioxidants, CoQ10, Vit D3, B-complex, and prenatal vitamins. Because of this, I have stopped taking my prenatals and CoQ 10. I also take Resvoxitrol which contains resveratrol. AND my Vit D came back extremely low so she prescribed vit D at a very high dose, 50,000IU once a week. BTW, I’ve noticed that (TMI) I have had loose stool that I never had before. My acupuncturist seems to think that it might be the side effect of DHEA. There is no way to prove it tho.

  2. Yet another outstanding post. I always look forward to your posts – selfishly of course, as a lot of this applies to me!. My specialist said he wasn’t convinced about DHEA but wrote me a prescription in case I wanted to get some (you need a prescription for it here in Australia, you can’t get it over the counter). He left the decision up to me. My husband and I decided against it, mainly because it apparently takes a few months to take effect anyway, and we were only weeks away from starting our IVF cycle. Depending on how this cycle goes we may consider taking it in the future. Like you say, for “well-informed” and consenting women. Thank you again for the research you did. Take care.

    Reply
    • Aw shucks!

      And that’s nice that your specialist gives you the information, but then lets you decide. I think you made the right decision. Hopefully you’ll never need it!

      Reply
  3. Yeah, so far so good with our doctor. I may be jumping the gun here but he has been incredibly sympathetic and great to deal with so far. He answers emails and even called me at 9pm one night as he knew I was sweating on my AMH test results and didn’t want me to have to wait until the next day. There’s a video of him in this link: http://ivf.com.au/ovarian-reserve-amh-test – that’s him explaining AMH down the bottom of the screen. I hope the DHEA goes well for you. Sometimes I think every little bit counts! I’m still doing acupuncture 🙂

    Reply
  4. It’s funny, about the soft sciences. We spent 18 months ttc. I had one pregnancy that ended as a miscarriage with bleeding starting from day 27 on. While temping I noticed that my luteal phase was 10 days. Against everything I had been taught I turned to the soft sciences. I found anecdotal evidence that Vit B6 can extend the luteal phase by a few days. So, I took it on the it can’t hurt principle. The very first month i took it I got pregnant and this pregnancy has been sticking (week 13). Interestingly in the cycle that I got pregnant I noticed an implantation dip at 12 DPO, and a triphasic temperature pattern for that month. I know as a scientist that this is anecdotal and not in any way evidence, it could be a total coincidence… but as an infertile I would swear it is magic!

    Reply
    • Very interesting! I also have a relatively short luteal phase. I can’t remember; did you have a specific IF diagnosis?

      Reply
  5. Wow, I had no idea that it was the same damn research team behind 90% of all the positive stuff that I was reading about DHEA on the internet. And that they had a financial stake. Sigh. Bubble popped. But good to know. I’m still on it, and we’ll see how that works out in my next IVF, but for some reason my RE didn’t want me taking that and CoQ10 at the same time. Any idea why? They don’t seem to contraindicate each other. Anyway, thanks for another awesome informative post!

    Reply
    • Maybe your doctor is a scientist at heart! She/he wants to know which supplement worked when you get 20 excellent quality eggs the next time around! 😉

      Reply
  6. As long as you’re giving soft science a try…yoga is great. It’s relaxing and can increase blood flow to the reproductive areas which in theory increases fertility. If you want I can send you the yoga routine I do for fertility.

    Reply
    • Thanks. I should give it a try again. Unfortunately I’m super inflexible which is why I haven’t tried it in years…

      Reply
  7. Oh, I tried to take L-arginine (also for my blood pressure, actually) but my nutritionist wanted me to take it as a powder mixed into water or juice… it gave me the runs in a brutal way! Have no idea why it had that effect, but be careful with that stuff! I fully support the DHEA thing… although my RE also said it was a waste of time. But as you say, it’s not going to do any harm, so you may as well give it a shot.

    Reply
  8. Interesting stuff here. I opted to forego DHEA for my 2nd round because I feel like there isn’t enough data (for me) to warrant using it. Yes it wont “hurt” but do I really need that much testosterone? For any function in my body? FYI my DHEA level is normal. I found that for me the Thorne Perfusia-SR for L-Arginine works best since it is absorbed and metabolized by the body so very quickly. In two a day doses it needs to be better sustained. I’d also recommend Royal Jelly and Pine Bark – brand name for most studies is – Pycnogenol which is French maritime pine bark extract. We’ll see how well it all works for round 2 IVF in August. Good luck!!!

    Sure you’ve seen this link but just in case:
    http://www.colocrm.com/FertilitySupplements.aspx

    Reply
  9. Ok so how lame am I – I have NO idea how to edit a comment but I take back the Pine Bark as you are already on it! Just recommending the Royal Jelly 100%.

    Reply
    • I’m actually trying to take that one too, but they old me to only take on an empty stomach, and I keep forgetting to do it until I’ve already eaten!

      Reply
      • I am considering starting the Royal Jelly. Curious, why do they tell you to take it on an empty stomach?

  10. I have pill organiser envy. I need to get me one of those!

    Reply
  11. If your classes are any thing like your posts, I would love to be one of your students! Loved your comment about taking your opinion as Gospel!

    Reply
  12. In preparation for IVF #2 I took everything on your list except for the DHEA and pycnogenol and instead I took Royal Jelly and Maca. I am not the one with infertility (hubby is) but I took the supplements anyway because I thought it couldn’t hurt and I just wanted to cover my bases. I ended up producing 29 (23 mature) eggs for IVF#2 and for IVF#1 I only produced 12 (10 mature).

    Hope this works for you!

    Reply
  13. I love the science of your posts–I don’t understand it all, but it’s so interesting, so thank you. I’m taking a hiatus from the supplements. I took them religiously, but after we only received 1 immature egg on our last transfer, I’ve been kind of blase about the whole thing. Since I agree that they might help and probably don’t hurt, when our year is almost up (waiting for husband’s best chances at sperm), I’ll go whole heartedly back into them. But taking the supplements was a near constant reminder of the infertility and it was making me sad/frustrated.

    Reply
  14. I have pillbox envy too! But how do you divide them up if some of them need to be before food, during food, after food (drives me crazy!!). Does your pillbox have subdivisions for that? 🙂

    Reply
  15. Looking at your supplements list: 3 questions….1) was your CoQ10 Ubiquinol or Ubiquinone? 2) Did your doc recommend dosage? 3) pycnogenol – will it do me good to just start it now if my next ER is likely 6-8 weeks away?

    Reply
    • I’m so sorry I didn’t reply sooner!
      1) My bottle of CoQ10 doesn’t specify. But the two are just different forms of the same molecule. In your body, it should get converted between the two forms.
      2) It was the ‘other’ RE at the practice (“Dr. L”) who recommended I take CoQ10, and she did recommend the high dosage (which is higher than what CCRM recommends). I decided to just stick with it.
      3) Pycnogenol is just an extract that has a boatload of antioxidants in it. So there are other options that would accomplish the same thing…a high antioxidant diet, grapeseed extract, red wine 😉 etc. From what I can tell, there aren’t any good studies showing that any of these things work, much less how long to take them or what dosage. But I can’t help but think maybe it made a difference for me… So I’d say start it if you want to. I don’t think the CoQ10 or pycnogenol pose any known risk. (Except perhaps to your pocketbook…)
      Sorry I don’t have a more helpful answer!

      Reply
  16. Laura

     /  April 30, 2015

    I have a question I’ve yet to have answered. DHEA increases testosterone and DHEAs and Myo-Inositol decreases both. Both are good for egg quality. So how is that possible? If aken at the same time do they contradict each other.

    Reply
  17. andrea

     /  September 14, 2015

    In a new publication, Gleicher et al explain the reason for their low rate of live births. The introduction gives a good insight into fertility specialists’ decision-making processes and the discussion is enlightening with regards to choices for denominator in proportions reported. http://www.ncbi.nlm.nih.gov/pubmed/26348275

    Reply
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