Progesterone Use as Hormone Replacement Therapy: Myths, Facts and Solutions.

Following is a letter presented to the Townsend Newsletter and published June 2020:

Dear Editor,

RE: “Progesterone Use as Hormone Replacement Therapy: Myths, Facts and Solutions.” https://www.townsendletter.com/article/439-40-progesterone-as-hormone-replacement/

We wish to comment on interpretations of certain “facts” which may not be fully grounded. And there are some points that are great
Dr. Gary Huber DO makes a welcome point that transdermal bioidentical progesterone is the right form for safety and uptake. Progesterone can be
applied anywhere as there are receptors everywhere. It is disturbing, though, to have him emphatically make the case for transdermal
progesterone, but then claim that women should only dose to a certain small amount.

From J. Bowles author of “The Unselfish Genome” (1) “… progesterone is not just for the reproductive system but is also known as the
most neuroprotective substance known to man and this is why women recover from brain injuries much better than men….” And “maintaining high levels of progesterone is important for anti-aging purposes because it suppresses the pro-aging hormones of FSH and LH which skyrocket in men and women after the age of 50”.

Progesterone itself acts as an aromatase inhibitor as well as an inhibitor of 5-alpha reductase. It is an immediate precursor to cortisol and serves to replenish those adrenal hormones depleted by stress. It is the hormone that balances the excess action of adrenaline. (2) Generous levels of progesterone can turn off the symptoms produced by mast cell degranulation. (3) It is produced and used independently by the Schwann cells in the nervous system. (4) It is also produced and used in the brain independently as a neurosteroid. (5) Progesterone can stimulate the activity of estrogen by sensitizing receptors. Unless enough progesterone is used, the estrogen related symptoms dominate leaving the patient even more estrogen dominant than before.

Dr. Bronson is a biochemist who has spent years studying mechanisms of bioidentical molecules. The original molecular spectra obtained on progesterone with Dwight Smith, the former chair of Dept of Chemistry /Biochemistry at the University of Denver clearly distinguishes the nature of progesterone from synthetic, so called “progestins or progestogens” Her particular expertise involves the importance of progesterone and its profound effect on mood.(6) Ultimately the purpose of our work is to help women get balanced enough to trust their own intuition. I, and my scientific colleagues, reject the premise that many women can get calm with these baby amounts suggested by Dr. Huber.

Bioidentical hormones do not follow an exact path, though there are pathways to specific receptors. Nor can they be quantified exactly as each woman will metabolize them somewhat distinctly. Dr. Huber appears to think it’s recommended to dose exactly what the body makes without any consideration that not every mg is going to make it through the skin. The only route that provides 100% bioavailability is intravenous.

Depending upon the delivery system and the nature of the skin of the patient, the absorption can be highly variable. It is so important to have enough progesterone to fulfill its important functions. The ability to replenish stress hormones is a large demand upon progesterone.
(7)(8)(9) Testing hormones with urine, dried urine, blood spot, and saliva are all limited in their application because none identifies the success of the hormone to reach receptors and produce the intended effect. Only the clinical benefits of applied hormones can define the success of replenishment. If a bioidentical hormone replenishment protocol is going well then constant testing in unnecessary as the – woman’s symptoms will alert you and her. In the research world, blood levels are used as most gender hormones are loosely bound to blood proteins and available
to dock readily at receptors when called upon.

And it seems plausible to us, that a lifetime of too little progesterone relative to potentially more aggressive molecules, would set a woman up to being vulnerable to the oxidative stressors of aging neurons. (10) In Dr. Bronson’s clinical practice, many women have gotten off lifetime addictions
to benzodiazepines if they get enough progesterone. Enough has to used throughout the day- along with GABA, as it takes enough progesterone
catabolizing to allopregnanolone to dampen the GABA-AR, they work together; Without enough progesterone GABA can become neuro-excitatory
Additionally, allopregnanolone, which is the most neural active hormone is synthesized from progesterone by the sequential actions of two enzymes, 5α- reductase type I (5α-RI), which transforms progesterone into 5α- dihydroprogesterone, and 3α-hydroxysteroid dehydrogenase (3α-HSD), which
converts then 5α-dihydroprogesterone into allopregnanolone. (5)

References:

1) Bowles, Jeff, “The Unselfish Genome, The Unselfish Genome- How Darwin & Dawkins Missed The 2nd Half Of The Theory Of Evolution: New Research Identifies The Hormone Changes That Control Human Aging”, University Science Press.
2) Platt Michael “Adrenal Dominance” Clancy Lane Publishing, Rio Mirage, CA June 12, 2014 3) Zierau, Oliver et al “Role of Female Sex Hormones, estradiol and progesterone in mast cell behavior” Frontiers in Immunology June 2012.
4) Schumacher,Michael et al “Progesterone synthesis in the nervous system: implications for myelination and myelin repair” Frontiers in Science February 2012.
5) King, Stephen “Neurosteroids and the Nervous System” Spinger Science and Business Media LLC 2013.
6) Bronson, Phyllis “Moods Emotions and Aging: Hormones and the Mind-Body Connection” Rowman and Littlefield NY Mar 11, 2015.
7) Hertoghe, Thierry “Identifying Cortisol Deficiency” Townsend Newsletter, January 2018.
8) Jefferies, William Mck “Safe Uses of Cortisol” Charles C Thomas Pub Ltd; 3 edition (August 1, 2004).
9) Fugate Woods, et all “Cortisol Levels during the Menopausal Transition and Early Postmenopause: Observations from the Seattle Midlife Women’s Health.” Menopause https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749064/.
10) “A Lifetime of Progesterone” https://www.womensinternational.com/blog/portfolio-items/progesterone/.

Phyllis Bronson, PhD
https://www.phyllisbronsonphd.com

Carol Petersen RPh, CNP