Miscellaneous Comments

Mineral Metabolism and High Dose Progesterone


Over a year later women in recovery from the progesterone overdose of the WP are experiencing  bone loss, dental caries, and gum disease.  I asked Dr. Formby if progesterone possibly played a role. 


Progesterone in pregnancy doses (WP protocol) has many adverse effects on the body’s electrolytic homeostasis. One major regulatory system involves the hormone aldosterone (mineralocorticoid) secreted by the adrenal cortex. After binding to its receptor, the human mineralocortoid receptor (hMR), the hormone regulates electrolyte transport across epithelia. As I have described previously aldosterone regulates serum potassium/sodium and keeps blood pressure in normal range. In the heart aldosterone regulates the transport of calcium. Also brain express hMR’s and aldosterone here regulates transport of Calcium/Magnesium across neural membranes. Now remember that an agonist is an activator and an antagonist is an inhibitor. Progesterone has a very high affinity for binding hMR. At a concentration of 30 ng/ml nearly 75% of transactivation by aldosterone in inhibited. Thus progesterone is a strong hMR antagonist. 


During pregnancy, the plasma concentration of progesterone rises to very high levels (90-210 ng/ml) that exceed those of aldosterone by a 100-fold. This excess is diminished to 10-fold by the stronger plasma protein and red blood cell binding of progesterone. The conversion of progesterone by e.g. the kidneys to androgens and other metabolites could result in an enzyme-mediated protection of hMR from progesterone. Other progesterone liver and brain metabolites (tetrahydro-progesterones) have significant adverse biological effects with anesthetic, anxiolytic and anticonvulsant potency.


Overexposure to progesterone (besides affecting calcium metabolism) also suppresses the immune system. A major physiological function of high levels of progesterone during pregnancy is to suppress the immune system and prevent the fetus from graft rejection.


WP long overdoses of progesterone therefore is responsible for all the adverse effects you mentioned in your mail.




About concentrations. 

It is a general rule in biomedical research that concentrations of hormones used in cellular experiments must be as close as possible to those operating in living organism. Which means very, very low concentrations. Imagine you drop a piece of crystal sugar into a swimming pool. Of course the water never will taste sweet because the sugar has been diluted millions and millions of times. But if you have a sensitive sugar assay system the concentration can be measured. A hormone and its biological receptor. Here is another example. When you add two teaspoons of sugar to a cup of coffee you can taste the sweetness. One very, very small crystal of aspartame hardly seen by the eye gives the same taste of sweetness. Difference in concentrations? Millions.