Reductionist approach in 5-alpha reductase article.
As a biochemist who has studied the mechanisms and structural chemistry of bioidentical hormones for many years, I have an issue with the reductionist approach to using them suggested by some trained essentially in reductionist clinical medicine. This is regarding the interesting article "The Clinical Importance of 5-Alpha Reductase in Human Health and Pathology," by Alan McDaniel (Townsend Letter, June 2017.)
I wish to say that while I found the article intriguing in part, and scholarly, I firmly believe the same flaw is in this overview as in the article on men in Townsend a few months ago, advocating another potent drug, Clomid (clomiphene) that also isolated 5-alpha reductase as the primary, isolating factor that has to be managed reductively, sometimes with some very potent drugs. (The use of saw palmetto makes more sense, but first look at the chemistry below.)
There are much safer ways to create mechanisms of action for 5-alpha reductase inhibition and for aromatase inhibition at the same time. Progesterone is a key molecule for this. Using strong allopathic pharmaceuticals capable of many side effects is contra indicative for using bioidentical hormones simply and effectively, without micromanaging.
Dr. McDaniel cites "a small 'lovely study" on dutasteride" at NIH! Are you kidding? Dutasteride is an extremely toxic drug:
J Clin Aesthet Dermatol. 2016 Jul;9(7):56-62. Epub 2016 Jul 1. Adverse Effects and Safety of 5-Alpha Reductase Inhibitors (Finasteride, Dutasteride): A Systematic Review. Hirshburg JM, et al.
Finasteride and dutasteride, both 5-alpha reductase inhibitors, are considered first-line treatment for androgenetic hair loss in men and used increasingly in women. In each case, patients are expected to take the medications indefinitely despite the lack of research regarding long-term adverse effects. Concerns regarding the adverse effects of these medications has led the United States National Institutes of Health to add a link for post-finasteride syndrome to its Genetic and Rare Disease Information Center. Herein, the authors report the results of a literature search reviewing adverse events of 5-alpha reductase inhibitors as they relate to prostate cancer, psychological effects, sexual health, and use in women. Several large studies found no increase in incidence of prostate cancer, a possible increase of high-grade cancer when detected, and no change in survival rate with 5-alpha reductase inhibitor use.
5-Alpha reductase inhibition can be micromanaged and miss the point of homeostasis; the beauty of applied science at its best is to simplify not unduly complicate. Only in certain preposterously difficult cases should drugs like Clomid, finasteride, and dutasteride be used with bioidentical hormones
My brilliant colleague Jeffrey Bowles and I have been discussing these mechanisms a lot. This is what we both see in the structures below, starting with the beautiful molecule progesterone. The drug companies have altered the structure to make these patentable, toxic inhibitory drugs.
All three of the molecules below are 5-alpha reductase inhibitors and prevent testosterone from converting to DHT, the "bad" form of testosterone that causes baldness and prostate issues
According to Dr. Catalona at Northwestern, those who take Proscar (finasteride) and/or Avodart (dutasteride) for benign prostatic hyperplasia (BPH), if they ever do get prostate cancer it is a much more severe kind (higher grade) than the men who took nothing for BPH. It is my guess that progesterone will work for BPH and not have these nasty side effects
All hormones are best used transdermally in most cases. Oral progesterone forms an upper GI metabolite, 5-alpha pregnenedione, which is a first cousin of phenobarbital. That is why women with low estradiol levels who are vulnerable to flat-affect depression feel worse with oral progesterone. They get calm but not wiped out with enough transdermal. The calming dampening effect on the GABA-AR does not happen as well, if at all, with oral progesterone; women get sleepy before they get calm, probably because of this metabolite. With enough transdermal progesterone, spread during the day, (50-100 mg doses) but more at night, the calmness happens.
Saw palmetto makes sense; but it is an adjunctive, safer alternative in some of the case studies cited, not a primary way to use the pure molecules, which only go to specific receptors.
My book explains the mood biochemistry, written as a 'woman's journey': Moods, Emotions and Aging: Hormones and the Mind-Body Connection (Rowman & Littlefield), by Phyllis Branson, PhD.
Nature gave us progesterone.
Big Pharma plagiarized it and tweaked it to patent it and gave us finasteride (Propecia/Proscar)
... and dutasteride (Avodart).
Phyllis J. Branson, PhD
Biochemical Consulting Company
Biochemical Research Foundation, Aspen, Colorado
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|Article Type:||Letter to the editor|
|Date:||Aug 1, 2017|
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