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Progesterone and Pregnenolone: Two Ps in a Pod


July 23, 2014 | Published by

peas in a pod

Progesterone and pregnenolone are steroid hormones manufactured in several areas of the body: the adrenal cascade, ovaries and testicles. Progesterone is made from pregnenolone and both are metabolized into DHEA. In the adrenal cascade, pregnenolone is the first hormone to be made from cholesterol and progesterone is the second. Besides DHEA both can be converted into several other adrenal hormones, including the sex hormones, aldosterone and cortisol. Hormones like pregnenolone and progesterone are incredibly versatile, letting your body’s wisdom choose which other hormones it will make from them based on your individual needs.

With adrenal fatigue, sex hormone levels often fall because your adrenal glands are not able to manufacture adequate amounts. One key function sex hormones serve is to act as antioxidants that help prevent the damage caused by cortisol. The lower the levels of sex hormones, the more damage there is to tissues, especially when stress levels are high. This oxidative damage is one of the key factors contributing to rapid aging.

Both progesterone and pregnenolone have been used with success to ease premenstrual syndrome (PMS). This is not surprising considering that the most common cause of PMS seems to be too little progesterone and/or too little magnesium. The addition of oral pregnenolone or natural progesterone cream is often used as relief for the side effects and symptoms of PMS. Both pregnenolone tablets and progesterone cream are available from many health food stores and some pharmacies.

It is important to note that we are speaking of natural progesterone and not the synthetic tablet-form progestins typically prescribed by a doctor. Synthetic progestins can have many side effects and should be avoided. The reason most progestins have side effects is that none of them are exactly like the natural progesterone your body makes. The progesterone contained in progesterone cream, however, is usually a naturally-derived plant progesterone (phytoprogesterone) that has been converted into the same molecule as the progesterone in your body. In my experience, this form can be used safely by most women.

Use of progesterone cream for PMS typically involves rubbing 1/4 to 1/2 teaspoon cream into the tender areas of your skin (swimsuit areas plus the inside of thighs and arms) each morning and evening. Premenopausal women should apply it from the 12th day of the menstrual cycle to the 26th day (the first day of bleeding is counted as the 1st day). Post-menopausal women can use it for 21 days each month. A great resource for more information on this topic is What Your Doctor May Not Tell You About Menopause by Dr. John Lee.

Both pregnenolone and progesterone can be used to raise the hormonal levels in both men and women, and decrease some aspects of adrenal fatigue. Bypassing the very complex and energy consuming steps required to make pregnenolone or progesterone from cholesterol means fatigued adrenals do not have to work nearly so hard to keep hormone levels adequate. Using hormone replacement therapy for adrenal fatigue is an area that requires skill. Although some of the hormones mentioned here can be purchased without a prescription, I highly recommend using a physician familiar with hormone replacement in cases of adrenal fatigue. If you cannot find one in your area, try our Find a Practitioner section to see if we have someone near you.

Hormones work together in symphony to perform in the concert of life. To throw in a hormone here and another there in a haphazard way is like having a heavy metal band thrown in with an orchestra. Hormones are powerful engineers of body processes and balancing them calls for delicate precision. The timing, the quantity and the form of hormone used are all critical. It is best to work with an expert who will monitor your progress using laboratory tests. If you do embark upon this yourself, use caution: start low and go slow.

Dr. James L. WilsonAbout the Author: With a researcher’s grasp of science and a clinician’s understanding of its human impact, Dr. Wilson has helped many physicians understand the physiology behind and treatment of various health conditions. He is acknowledged as an expert on alternative medicine, especially in the area of stress and adrenal function. Dr. Wilson is a respected and sought after lecturer and consultant in the medical and alternative healthcare communities in the United States and abroad. His popular book Adrenal Fatigue: The 21st Century Stress Syndrome has been received enthusiastically by physicians and the public alike, and has sold over 400,000 copies. Dr. Wilson resides with his family in sunny Tucson, Arizona.

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  • Mark Newman says:

    Nice article, Scott and Dr. Wilson. Here is the question I keep coming to…when you say that taking progesterone helps to bypass the work in the adrenals to make progesterone on its way to cortisol, that makes sense…but does it happen regularly and predictably? What I mean is, do you actually get any cortisol when you take topical progesterone? As I understand it (which is not at a high level) the rate limiting step is to get cholesterol into the cell (star) and then it goes down the cascade to cortisol. This all happens within the cell, correct? So then do circulating levels of progesterone jump into the middle of that cascade? Do women make more cortisol in the luteal phase when progesterone is higher? Does circulating progesterone really go down that pathway in a significant quantity? I can’t find much on that. One reason I think some people think this happens a lot is that some prominent saliva labs formerly used cortisol tests that cross-reacted very significantly (>60%) with progesterone. So when progesterone got above a couple thousand (which of course it does all the time with transdermal Pg) the cortisol would artificially be raised. This led a lot of people thinking (especially one of the labs) that all this progesterone was metabolizing down to cortisol. I’m not saying that progesterone doesn’t head in that direction when given exogenously, but I haven’t found much in the literature where they looked at that. Are there any studies you have found on that? Love your work!

  • I have used pregnenolone for years with individuals with adrenal fatigue. What a great product and the benefits are far-reaching for many people, not only with fatigue, but mental health issues, sleep problems, focusing and attention issues, etc. Pregnenolone also being linked to cholesterol I encourage everyone to have Total Cholesterol (TC) tested as well and to try and maintain TC up around 180 to 200 as an ideal range.

  • Bee says:

    So what is a good brand and how does one dose?

  • Olga says:

    Hi Dr. Wilson’s team! My doctor has prescribed me progesterone tablets 100mg and I am supposed to start taking it this week. It’s a round orange pill that says AK on it. I researched it and it said it’s michronized progesteroneprogesterone. I still don’t understand synthetic or not. I got it from a Walmart pharmacy. Please help if you have any idea, should I take itit? Thank you.

    • Brandon Derrow says:

      Hi Olga,

      Did your doctor discuss the medication with you, as far as source, strength, etc. go? Some micronized progesterone pills are made from yams and are considered natural. We don’t know for certain if the one you were prescribed is natural or synthetic. We can’t tell you if you should take it or not, but if you have concerns we recommend you speaking with your doctor for more details or alternatives. Thanks for writing – we hope this helps!

  • Patricia Taylor says:

    Helpful information! Thank you Dr. Wilson….
    Your thoughts…. Can I use pregnenolone cream once a day .15mg in addition to using my progesterone crean plus estriol? They are combined in one cream giving me 20mg of progesterone to 0.75mg of estriol. My current levels are just using the progesta care plus estrio and nothing else I often add in extra progesterone with my morning and evening pump 10 mg. Having difficulty with night sweats and major sleep disturbances. So could I incorporate the pregnenolone cream to find a better balance. My other thought was to stop the estriol and just use the progesterone cream w/pregnenolone although I don’t know if I need the estradiol…… I am unsure if my estrogen levels just right, to high or to low. I am 54 in my 2nd year of NOT menstruating. My OBGYN will not condone the use of natural hormone replacement only synthetic which I WILL not use. Thank you!!
    E1 46pg/ml
    E2 24.0 pg/ml
    Testoterone 8 ng/dl
    Free Testoterone 0.2 pg/ml
    Progesterone 1.0

    • Patricia Taylor says:

      Dr. Wilson I also wanted to include my DHEA level 60.8 ug/dl

      Thank you

    • af says:

      Hi Patricia,

      Dr. Wilson is no longer in practice and cannot provide medical advice or consultations. We would not be able to make recommendations on taking pregnenolone cream. Since you would be adding hormones to your body, your best bet would be to consult with your practitioner or pharmacist on this question. If you would like a referral to a healthcare practitioner, we may be able to help. Thank you for writing!

  • Ann Parkins says:

    I want to stop taking my progesterone tablets. I have been on them for 20 years under a Doctors care. The tablets are prescription only. I have moved and changed Doctors. I tool a saliva test . The results were that my progesterone was low despite the fact I was taking progesterone, 75mg every night. My new Doctors wants me to stop taking progesterone and start taking pregnenolone; 30mg in the morning and 30 mg at noon. I read that pregnenolone can cause hair loss. I started taking pregnenolone but I have only been taking 30mg in the morning because I do not want any hair loss. I am a very healthy and fit 70 year old. So what do you think about pregnenolone instead of the progesterone tablets? Your opinion would be appreciated

    • Adrenal Fatigue Team says:

      Hi Ann,

      Unfortunately we are unable to offer medical advice and wouldn’t be able to advise you on your hormone use. If you are looking for a practitioner in your area to consult with we may be able to help. If so provide us with the area. You can also email us at for help in finding a practitioner. Thanks for writing!

  • Jeanne says:

    keep taking the progesterone cream for bone loss as i am you age and take it for that.
    Dr lee said it in his book what your doctor does not tell you about progesterone.

  • Claudia Caselli says:

    I have found pregnelonone cream v helpful in preventing menstrual angina,and pmt…I think, for me it raises my oestrogen levels..which I think r low.However I have unfortunately experienced a v negative side effect of using this cream..even at relatively low dose,it causes blood clots in my legs..which am predisposed to.Also recently it has made my PAD worse..feet discomfort in the night is worse.So I have to use the minimum amount of cream as poss.

    • Mary Thomas says:

      Hello to Dr. Wilson’s team! I am in great need of a referral to a good doctor who understands the need for natural hormone replacement therapy in the context of advanced adrenal fatigue.

      I currently live in NW FLorida, but often travel to Atlanta, Ga. Willing to drive within a 3 hour radius from NW Florida and also to Atlanta.

      Can you please help me?

    • Jennifer says:

      You need to use a minimum of 100-200mg progesterone cream daily otherwise you activate the oestrogen receptors and put yourself at risk for estrogen dominance. Look up Dr Wray, she explains this well.

  • Dana says:

    Dear team

    Could you please send me some referrals for Auckland in New Zealand? Thanks a lot!

  • Dai says:

    Hello Team!
    I understand from previous posts that Dr. Wilson is no longer available to offer advice. Could you provide me with information on any practioners, or a referral to a specialist in my area, Halifax l, Nova Scotia, Canada? If there are not any in my province (state), I am willing to travel within Canada, as well as the Unites Stated if necessary.
    Thank you so much!

  • Jill says:

    Hi please send information of a Dr. in my area that could help with my son and his hormones.

    Thank you so much.


    • Adrenal Fatigue Team says:

      Hi Jill,

      Unfortunately we do not have any practitioners in the Colorado Springs area. Are there any other areas you’d like us to search?

  • Jill says:

    I’m sorry we live in Colorado Springs, Colorado!

    Thank you


  • Josefina says:

    Have been reading this thread … the article and comments
    Confirm i am in the right place.
    Please send practioner referrals (adrenal, menopausal low testo, DHEA. Have had great success with Estriol and progest (bioidentical) … but two major WRONG turns with docs that overprescribed (hormones i did not need) … after one dose i knew the reactions were not about adjustment … but actually setting me up for serious problems.
    Now a couple of years later i have had great things happen
    With progest and estriol … and via nutritional panel (low d3) and more see that adrenals are maybe 1/2 healed … but my testo and dhea remain low.
    Thank you for any guidance and direction you can provide!

  • Josefina says:

    Ps. All hormones i mentioned / have experienced are
    Bioidentical (non synthetic).

    Thanks again!

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