Pregnenolone Supplementation Risks/Benefits

Today, I'm starting a series of posts where I review each of my supplements to explore the risks, benefits, and doses of each. For each, I'll weigh the pros and cons and try to determine "the ME/CFS web world's" consensus on the topic. To be clear: I have no medical training -- I am simply summarizing what I've read on the internet. 

I'll start with hormone supplements since I've heard that messing with the endocrine system is fraught with peril.

First up: Pregnenolone.

Why Supplement Hormones for ME/CFS?  

The theory is that ME/CFS is a multi-system disorder, pointing to a defect in the hypothalimus.  The hypothalimus controls the endocrine system (hormones), immune system, nervous system, and mitochondrial energy.  Many ME treatment plans call for simultaneous support of all four systems as a way of, sort of, taking the stress off of the hypothalamus, allowing it to start functioning properly on its own again.

Personally, my pregnenolone levels were one of the lowest of all my hormone levels when tested in December.  The lab's reference range is 13 to 208 ng/dL.  (The reference range for males is 10-200). (Citation) Mine was a mere 23 - in the bottom 5%.

What is Pregnenolone? 

Pregnenolone is a steroid hormone the body makes as a precursor (the raw material) for other hormones, such as progesterone, DHEA, mineralocorticoids (which regulate electrolyte balance), corticosteroids (which influence inflammation and metabolism), estrogens, and testosterone. (Citation)  Basically, it's the essential building block of the other steroid hormones.

Risks / Concerns  

According the the American Cancer Society, "Very little is known about the safety of the supplements or the effects of long-term use. Some laboratory studies in cancer cells and animals have suggested that pregnenolone may stimulate the growth of hormone-responsive cancers such as prostate and breast cancer....High doses may cause aggressiveness, irritability, trouble sleeping...It also may...lower the levels of HDL, or "good," cholesterol, which could raise the risk of heart disease. Other possible side effects include acne, heart rhythm problems, liver problems, loss of hair from the scalp, and oily skin." (Citation)

I have also read that weening off of Pregnenolone supplementation can cause depression.

I have concerns about increasing any "steroid" as steroids tend to decrease immune response.  I am not certain, however, if this applies to "steroid hormones."  It turns out, this is a very complex question with no clear answers.  Thus far, only animal studies have been conducted on this topic, but those studies found that steroid hormones actually  boost immune response.

I also worry that the increased pregnenolone will convert to female hormones such as estrogen and progesterone.  Once inside my body, how do I know which hormones it will convert into?  On the other hand, this website claims that that concern is unfounded.

Possible benefits  

Pregnenolone is supposed to be a powerful memory aid and enhancer of cognitive function.  I can state from experience, this seems to be true.  Within a few days of beginning 100 mg dosages of pregnenolone, I started having exceptionally productive and clear headed days.  I felt very mentally alert.

Other sources making a strong case for the benefits of pregnenolone supplementation are here, and here.

For what it's worth, pregnenolone is sold as an over the counter supplement.  Anyone can take it in any amount, which tells me it's side effects can't be too harmful.  Right...?

Dosage 

Dosage recommendations are all over the map.  Because Pregnenolone is a supplement and does not require FDA approval, nobody has ever established dosage limitations. (Citation).  My doctor prescribed 100 mg/day.  Dr. Tietelbaum also recommends 100mg.  I've seen recommendation of as high as 200mg.

On the other hand, pregnenolone is typically sold in maximum quantities of 50mg, and several sources state that the correct dose is a mere 5 to 30mg, with frequent "holidays" to give your body time to start anew.  This doctor insists that the correct dosage is only 1-5mg, and that higher dosages are unsafe, but he doesn't provide any citations to research.  The bottom line is, there is no consensus.

Pregnenolone is supposed to be taken first thing in the morning, before a meal.

My Conclusion  

I remain uncomfortable with the idea of supplementing pregnenolone in the long term, especially at dosages of 100 mg.  But I will at least continue taking it until my next doctor's appointment in two months, and then talk to my doctor about reducing the dosage to something minimal, like 10mg, with regular "holidays."

If I continue to take it for more than, say, one year, I will begin regularly testing my levels of dihydrotestosterone, to ensure that it is does not enlarge the prostate.