Here is a response from Dr Mariano (a highly regarded Neuroendocrinologist) regarding progesterone:
To examine the possible side effects of Progesterone, one has to look at Progesterone’s roles.
Progesterone is a precursor for testosterone, estradiol, cortisol, aldosterone, and allopregnenolone and allopregnanolone, etc… Progesterone is broken down to Pregnanediol (inactive) after it is used.
Progesterone is the precursor for testosterone in the testes. Increasing testosterone production requires increasing production of progesterone, its precursor. hcg can increase progesterone production in men. If the increase in progesterone leads to an increase in testosterone, this can have good or bad effects. Bad effects include slowing down the adrenal glands when one already has adrenal fatigue, excessive acne or hair loss, etc.
Progesterone is a precursor for estradiol. Progesterone also increases the number of estrogen receptors. Either one can lead to signs of excessive estrogen signaling (e.g. gynecomastia, aggressiveness, fatigue (from lowered thyroid hormone in response to increased estrogen signaling), loss of libido, etc. even if Estradiol is controlled (since the signal is stronger when there are more estrogen receptors).
Progesterone is a precursor for Cortisol. In women, it is a good replacement for hydrocortisone (cortisol). Generally, this doesn’t lead to excessive Cortisol, since cortisol is made on demand.
Progesterone is a precursor for Aldosterone. This usually doesn’t lead to an excess in Aldosterone since Aldosterone has other controls - such as salt-balance.
Progesterone is a precursor for Allopregnenolone (both in brain and liver), and Allopregnanolone (in brain). Allopregnanolone is neuroprotective. This is how Progesterone can be useful in stroke - to reduce nervous system damage from a stroke. Allopregnenolone increases GABA receptor sensitivity to GABA. This is how Progesterone helps reduce norepinephrine signaling, how Progesterone can be sedating and anti-anxiety, and how Progesterone can be used as an antiseizure medication. Excessive allopregnenolone can cause excessive sleepiness, loss of libido (since libido also depends on adequate but not excessive norepinephrine signaling - which gives us sexual excitement), impaired concentration, fatigue (since norepinephrine also is a signal for energy on demand), etc.
Progesterone also reduces estradiol’s inhibitory effect on thyroid hormone. I speculate that this may involve reducing thyroid binding protein production. Thus, possibly this can lead to excess thyroid signaling for those sensitive to thyroid signaling - such as those with adrenal fatigue.
Progesterone also may reduce blood pressure. Dizziness may result from excess.
Progesterone is also a 5-alpha-reductase. This blocks testosterone to DHT conversion. Excessive progesterone may thus mean a reduction in body hair, acne, etc. - among other actions of DHT.
I suppose you mean a 24-hour Urine Steroid Hormone Profile from RheinLabs.com when you say “rhein’s test”.
I suppose you mean transdermal when you wrote “TD pregnenolone.”
Taking pregnenolone before a 24-hour urine hormone profile depends on whether or not you want to see the effects of pregnenolone on one’s hormone metabolism. You would need a before an after test.
Since Pregnenolone is a precursor for nearly all of the substances tested, it can raise the level of any one of the substances it is a precursor to. Depending on the person, this may mean elevated testosterone and precursors or elevated progesterone and Pregnanediol, elevated Cortisol, or any other one or a combination of these signals/hormones.
If one has ongoing treatment with Pregnenolone, then it would be useful to monitor its effects on hormone production by taking it while undergoing the hormone profile test. For example, I would want to know if Pregnenolone is converting excessively to Estradiol, resulting in destabilization of mood in some patients or impaired muscle mass gain in others.