Is DHEA making me fat?…Why my ovaries are like dogs…And other stories.

Has anybody else put on weight while on DHEA? I’m up ~4 pounds since midsummer (and ~7 since 15 months ago when I was pregnant, but I can’t really blame DHEA for those extra 3 lbs…) DHEA is an anabolic steroid, and anabolic steroids cause weight gain, so I think it’s possible. The other reason I’m inclined to blame the DHEA is because of where the weight has been going. Not to my hips, thighs and butt (like usual), but straight to my belly. I have a beer gut. And now that I have to start dressing professionally again, all my work clothes are either unflattering, uncomfortable, or both. Ugh.

So, as you all know, we had our phone consultation with Dr. Schoolcraft on Monday. Overall, it went pretty well. (You can find his answers to my long list of questions here.)

Here are some other tidbits from our conversation with Dr. Schoolcraft that didn’t directly pertain to our questions:

  • Dr. Schoolcraft was late. He called us almost 40 minutes after our scheduled time. This wasn’t so much a problem in itself (the nurse had warned us that it was often the case), but – ever the healthcare practitioner – C pointed out that if he was that far behind schedule (it was 5:40pm his time), he almost certainly didn’t stop to look over our file before he called.
  •  Judging by the conversation, Dr. Schoolcraft almost certainly hadn’t reviewed our file. Again, this might have been fine in itself. (His answers were thorough, and he didn’t make us feel like he was in any rush.) But we found it annoying that we went to so much trouble to get our records, and to fill out an annoyingly detailed (and poorly designed) health history form online, if he wasn’t even going to read it. And, we now have one more question…which wouldn’t bother us if we felt like he had actually read our file before calling. (Specifically, we spent a lot of time with him talking about low-stim versus high-stim, the underlying assumption being that we had only tried low-stim and don’t know what would happen if we increased the dose…somehow we all forgot to consider the fact that we in fact tried IUI with pretty high doses of Menopur – 5 vials per day – and only got 2 follicles developing. I know that IUIs are different – I couldn’t take stims for as many days because I wasn’t taking anything to suppress ovulation – but still, the scientist in me is frustrated to think that we neglected an important piece of data!)
  • Dr. Schoolcraft thinks I have a “poor prognosis”. He just sort of let that slip out in the context of some comments about comparing SART stats between clinics. Not that it came as any big surprise, but it was more direct than Dr. Y has ever been (though not as bad as when Dr. L said I would go through menopause before 40…) I think it’s a good sign; it’s consistent with what I’ve heard from other patients (who described him as “direct” and someone who “doesn’t mince words”) and the last thing I want is a doctor who’s going to blow smoke up my ass…but it still stung.
  • I thought Dr. Schoolcraft’s advice for comparing SART stats was very interesting. He mentioned (and I’d heard before) that some clinics manage to inflate their stats by refusing to take patients with a poor prognosis (especially older patients). His advice, therefore, is to compare the ‘% of cycles resulting in live birth’ specifically for women under 35 (where there will have been the least selection bias). If you want to compare the quality of different embryology labs, then look at the success rates for donor cycles. It’s not perfect, but I thought it was an interesting way to get around some of the stat manipulation.
  • Naturally, the first thing C and I did after getting off the phone with Dr. Schoolcraft was to compare the SART stats for our local clinic to those for CCRM in the categories of women under 35 and donor cycles…and while CCRM was better on both counts, there really wasn’t a huge difference. So our lab really does seem to be quite good. But we also considered Dr. Schoolcraft’s point that CCRM sees mostly out-of-state patients who have already failed one or more IVF cycles. In other words, they see a disproportionate number of ‘hard’ cases. And yet, their stats (in just about every age group and diagnosis) are higher than anybody else’s I’ve found. This seems to back up Dr. Schoolcraft’s claim about having the best lab.

So, despite our mild annoyance, and “poor prognosis”, C and I decided that we should at least make the appointment and do the one-day workup. It’s not cheap, but it’s thorough, and after getting the results, we’ll be able to have a better sense of whether it’s worth our time to continue with my eggs…

C made the point that every month to my ovaries is like years to a normal set of ovaries. (My ovaries are like dogs, apparently.) And also reasoned, “We’ll probably spend money on a lot stupider things.”

I’m not feeling very optimistic about our chances of getting pregnant – even at CCRM, but it feels like something we have to do to feel like we’ve done everything we can.

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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’…)

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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!

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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.

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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…

Inspiration…and testosterone

Since starting this little blog, I’ve enjoyed finding other bloggers to commiserate with. But in finding bloggy friends, I’ve done my best to avoid blogs of people who were already pregnant. (Exceptions include Vanessa at Yeah Science! – the name of her blog was just too tempting,  and JoJo at An Infertile Road, my very first follower, who got pregnant – on her first IUI! – while I was following her.) I avoided pregnant bloggers because I wanted to shield myself from having to think about pregnant women, a sentiment that Jenny at Dogs Aren’t Kids expressed so well in a recent post.

The problem with this strategy – at least for me – is that it didn’t leave much room for optimism. I loved that there was/is no shortage of support and excellent company in my misery…but I also found myself doubtful that treatment could work for me. I mean, it didn’t seem to have worked for any of my other bloggy friends, so who was I to expect that it would work for me?! (Another problem with this strategy is that it makes me a little bit afraid of actually getting pregnant – like this amazing support system will suddenly vaporize as all my new friends go running for the hills!)

Since my last post, I took advice from Kimberly at No Good Eggs and joined my local Resolve support group. I haven’t been to a meeting yet (the next one is November 19th), but I joined their online forum. On this forum I found inspiration in the form of a Protocol Buddy – someone who followed my weird IVF protocoland had the same baseline AFCand got pregnant! And she writes a blog! I am so encouraged!

Furthermore, this experience gave me the courage to face my fear of pregnant infertility bloggers, and I started reading Jen’s blog, Overworked Ovaries. (Jen’s name and cute avatar kept popping up in the comments section on all my favorite blogs, with hints that her infertility issues might be similar to mine.) I’m about halfway through reading her posts (oldest first), and I find it so exciting to read a story that I know has a happy ending! It’s also great to see that so many of her awesome bloggy friends haven’t abandoned her, but are following along and cheering her on through her pregnancy. And I can’t help but think this is what it’s about! This is what I want!

And I feel hopeful.

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Now, let’s talk about testosterone. But first, the disclaimer:

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 complicated treatment protocol!

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Last night I applied my final Androderm patch. The night I applied my first patch, I noted first that it is weird looking. C calls it my third nipple.

ImageI wasn’t exactly sure how to apply it, so I checked the website. Clearly they are not marketing to women trying to get pregnant:

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I couldn’t help myself, and decided to check out the website for Estrace cream for comparison:

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I’ll leave it to cleverer folks than me to comment…

Anyway, I waited to write about the testosterone-priming until now, partly because I was hoping dreading expecting to observe some side effects. I observed none. This fact makes me a bit skeptical that this low-dose patch would actually do anything for a 200+ lb man with low sex drive. Then again, that’s not why I am taking it.

And why am I taking it?

From what I can tell, the use of androgens (broad term for male sex hormones including testosterone and DHEA) to treat infertility patients is pretty new, and pretty controversial. Most of the papers I read were written by physicians at the same few clinics. But I think the gist goes like this:

  • Recent studies suggest that Diminished Ovarian Reserve is a condition characterized by the reduced ability to make androgens (including testosterone). This correlation seems to be especially strong in younger DOR patients. (Interestingly, several of the papers contrast DOR with PCOS, a condition characterized by overproduction of androgens…)
  • Testosterone is produced in the ovaries, in ‘theca cells’. Testosterone from the theca cells enters the ‘granulosa cells’, where it is converted to estradiol. (You can read more about estradiol in this post.)Image
  • Granulosa cells are the cells that surround the developing follicles and help prep and develop the eggs for ovulation.

The thought is that in theory [insert head tilt and two-handed gesture] since DOR patients can’t make as much testosterone, supplementation (through a gel or patch, or indirectly by taking DHEA – a testosterone precursor), will stimulate the granulosa cells to do their thing and prep those eggs. This is supposed to “enhance follicle recruitment” (more eggs) and “promote follicle growth and development” (better eggs).

At least a few studies seem to support this theory, showing a greater number of large follicles and better overall pregnancy outcomes for DOR patients treated with androgens (versus untreated DOR patients).

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I start stims (Clomid 100 mg + Menopur 150 IU) tonight, so I guess we’ll see!