“It starts with the egg”, Rebecca Fett, 2014, ISBN 978-0-9911269-0-3
This book review is actually just a chapter review. Chapter 2 of this book is titled “The dangers of BPA”. That in itself was enough to tell me that although this book is presented as a well-researched, evidence-based, non-biased view of the science of egg quality, it may be something less than those lofty ideals. So I skipped to the chapter on DHEA.
I read the chapter on DHEA in detail and checked most of the references therein (ignoring those regarding miscarriage and dosing). This was sufficient for me to not recommend this book to anyone else. Upon initial reading it does seem like the author has done a fair deal of research and analysis, but it is also easy to see that results are highly overstated: eg. “extraordinarily successful results from the use of DHEA” pg. 171. Not every fertility specialist will suggest you take DHEA for low ovarian reserve and that is because there are NO extraordinary results. Instead, there are quite a few studies with potentially interesting preliminary results but each of these studies has serious limitations and should therefore be taken with a grain of salt. Even an abundance of such studies does not constitute convincing evidence. For now i’m going to assume that anyone reading my blog is interested in an evidence-based view of the DHEA literature and has a basic understanding of how to assess clinical data including a basic understanding of statistics. It appears that Rebecca Fett does not. Either that, or there is wilful manipulation of information. This is illustrated by certain errors such as the following:
On pg. 156: “Because it [DHEA] is a precursor to estrogen and testosterone, when taken as a supplement it can increase the level of these hormones in the ovaries.” The citation given for this ‘fact’ is Wiser et al. 2010*. The findings in this article are: “The DHEA group demonstrated a non-significant improvement in estradiol levels on day of hCG (P[sic] = 0.09)”. This is hardly evidence that DHEA supplementation resulted in increased estradiol and therefore shouldn’t be used as a source for the quoted ‘fact’. Additionally, the article does not mention any testosterone measurements whatsoever.
The most interesting citation has to be an actual, prospective, placebo-controlled, randomized trial of DHEA (as proudly stated in the article title**). In this case, Fett has correctly cited this article to show their finding of more developing follicles in the DHEA treatment group as compared to the control group. Although, Fett states this finding occurred “after three to four months”. What the data actually shows is one statistically significant finding after 12 weeks of treatment, but the groups were no longer different at 16 weeks or 20 weeks (DHEA or placebo was taken for 16 weeks). This pattern of one significant finding amongst many weeks of no difference is not explained or accounted for. Wouldn’t you expect the effect to be cumulative? Fett implies as much throughout her chapter. Additionally, it can be seen that the size of the ‘effect’ or difference was very small, with the DHEA group showing 1-5 antral follicles and the control group showing 0-2. A sense of the natural variation can be seen with the placebo group, with results of between 0-4 antral follicles over the study period. As can be seen from Fig. 5 in the article, these results equated to 2 women having at least one follicle >10mm at week 12 compared to none of the women in the control group. No statistical analysis was carried out on these ‘percentage of women having at least one follicle >10mm’ comparisons.
This seems to be another small hint towards real evidence, helped by the study design but hindered by the size of the study. Luckily, the same authors have published a slightly larger study that looks eerily similar, just a few months after the initial study***. Unfortunately, this time no difference was found between antral follicle count at week 12. At least this time these authors suggest caution in interpreting their results due to the still small sample size. This second article was published after Fett’s book, although the conclusions had already been published in an abstract here:
Basically, at the time of publication of Fett’s book there was little in the way of quality data to support a recommendation of DHEA to women with low ovarian reserve/POI. Fett does admit as such, and mentions that this treatment is therefore criticised. At this point Fett raises an analogy to folate, but it is a very confused analogy.
“Thirty years after the initial discovery of folic acid’s benefits, we know that the early doubts about the value of folic acid in preventing birth defects probably caused many tragic outcomes that could have been avoided if medical advice had kept pace with research.”
This is an unfounded and backwards comment and once more seems to be either an inadequate understanding of the source material**** or a manipulation thereof. It’s true that a proper trial of folate was delayed 10 years but this was because the medical advice was to take folate supplements, even though the evidence was lacking. This is clearly the direct opposite of the current situation with DHEA. The ‘controversy’ mentioned in the articles cited by Fett had nothing at all to do with the ‘doubts about the value of folic acid’ but rather the opposite. Perhaps Fett has been confused over a more highly discussed controversy regarding folic acid/folate, which is the question of whether basic foodstuffs should be supplemented with this chemical so that all women are thereby ‘supplemented’ whether they are procreating or not.
In short, this book does not present a rigorous analysis of the available science and is written from the emotive standpoint of ‘those trying to conceive should try anything that may increase their chances’. I know that is a common standpoint in the infertility world but doctors are rightly wary of selling false hope, and I for one am grateful for that.