Natural Progesterone Safety

Natural progesterone is quite safe because it is the same molecule your body uses in each menstrual cycle. Natural progesterone is the molecule that your body uses to maintain pregnancy. Pro-means "for". Gesterone-means for "gestation". Thus, progesterone means "for gestation". Your body makes 20 mg of progesterone a day during the latter half of the menstrual cycle. During pregnancy, your body starts off by making 20 mg of progesterone by the corpus luteum. Then, during the second and third trimesters of your pregnancy, your body makes 400 mg of natural progesterone per day. If you don't have enough progesterone during the first trimester, this will cause a miscarriage of the baby during the weeks of gestation five through eight. Also, if you are allergic to progesterone, your body will eat up the progesterone via antibodies and this may result in a early preterm delivery according to 
Beer, MD.  

Thus, you and your baby are exposed to high levels of progesterone during pregnancy. Also, there is a wide therapeutic range in which progesterone is effective as a therapeutic agent. Anywhere from 20-400 mg/day.  Also, natural progesterone is safe for both you and your baby in large quantities. What do we know about women who have been pregnant multiple times and delivered (maybe 9). These multi pregnant women have a smaller chance of breast cancer and endometrial cancer. It is thought that estradiol induces proliferation of non-differentiated breast cancer cells, and progesterone induces differentiation of breast cancer cells.[1]   The Woman's Health Initiative with its 29% higher rate of breast cancer for PremPro users was a shocking statistic to many in the mainstream medicine world. The following excerpt is from John Lee, MD's book, "What Your Doctor May Not Tell You About Menopause".

Evidence for Hormone Deficiency or Excess As A Risk Factor For Cancer

Let's look at evidence that shows hormones deficient or excess can act as a risk factor for cancer:

1. Breast cancer is more likely in premenopausal women with normal or high estrogen levels and low progesterone levels. This may occur early adult life, but more often occurs after the age of 35, when anovulatory periods are common.

2. For premenopausal women, breast cancer recurrence or metastases after mastectomy is more common when surgery was performed during the first half of the menstrual cycle as compared to when the mastectomy had been performed during the last half of the cycle. The last half of cycle is when the woman usually produces progesterone. This begs the question, why surgery is not performed during the progesterone or luteal phase of the menstrual cycle. This also makes one wonder why transdermal natural progesterone is not prescribed before surgery.

3. Tamoxifen, a weak estrogen that goes into the estrogen's receptor and blocks stronger estrogens, is prescribed after breast cancer surgery to prevent breast cancer recurrence.

4. Pregnancy before the age of 30 is known to have a protective effect against breast cancer. Natural progesterone is the dominant hormone during pregnancy.

5. Only the first, full-term, pregnancy gives protection against breast cancer. Women pregnant before the age of 18 have one third of the risk of women pregnant with their first child after the age of 35. Interrupted pregnancies that include miscarriage or abortions do not give this protection.

6. Women without children are at high-risk for breast cancer compared to those with one or more children.

7. Women that underwent an operation to remove both ovaries, ooprhectomy, before the age of 40 have a significantly reduced risk of breast cancer.

8. The protective effect of oophrectomy for breast cancer is canceled by giving them estrogen.

9. Treating males with estrogen is associated with an increased risk of breast cancer.

10. Herbs and chemicals that mimic estrogen, called xenoestrogens are widely recognized as a ubiquitous threat to creating more breast cancer. You may visit the www.breastcancerfund.org for more information on chemicals that act like estrogen that are suspected of computing to breast cancer risk.

11. Breast cancer, ovarian cancer, and endometrial cancer is more likely in women that are receiving mainstream "hormone replacement therapy," that combines estrogen or a synthetic estrogen with a synthetic progestin.

Estradiol Causes Proliferation, Natural Progesterone Causes Differentiation

Estradiol's purpose in the uterus is to cause proliferation of the lining of the uterus. Estradiol makes the endometrium or cells on the lining of the uterus multiply faster during the first half of the cycle. Later, natural progesterone comes on the scene, and causes the maturing or differentiating of the cells on the inside of the lining of the uterus. This maturing of the cells in the incentive lining of the grass prepares the inside of the lining to receive the embryo. So, essentially, estradiol, tells the cells to make more baby cells. Progesterone stimulates the cells to grow up and become mature. Breast cancer cells are baby cells. Breast  mature cells, differentiated cells, are not cancerous. Progesterone promotes differentiation and is one way that progesterone protects against cancer.

Scientific Studies Showing Estradiol Causing Proliferation and Natural Progesterone Causing Differentiation

Three studies have shown that progesterone protects against cancer. Foidart in Fertility and Sterility in 1998, summarized, "Exposure to progesterone for 14 days reduce the estradiol induced proliferation of normal breast epithelial cells in vivo." Malet in  Journal of Steroid Biochemistry and Molecular Biology in 2000, summarized, "Cells exhibited a proliferative appearance after estradiol treatment, and return to a quiescent appearance when progesterone was added to estradiol. Progesterone seems to predominantly inhibit cell growth, both in the presence and absence of estradiol."

One of the best studies demonstrating action of estradiol and progesterone on cell proliferation was a study by Chang in 1995. Chang tested transdermal estradiol and transdermal progesterone applied to normal human breast duct cells. Human breast duct cells are where most breast cancers come from. He had four groups of healthy young women that underwent minor breast surgery for benign breast disease. The young women rubbed the transdermal hormone creams on their breast 10 to 13 days before breast surgery.

1. Group A used 1.5 mg of estradiol in a cream daily.
2. Group B used 25 mg of natural progesterone in a cream daily.
3. Group C used both 0.75 mg 12.5 estradiol and natural progesterone in a cream daily.
4. Group D used the placebo cream.

At surgery biopsied tissue was measured for estradiol and progesterone concentrations as well as cell proliferation rates. Blood plasma hormone levels were also taken. The biopsied tissue was viewed under a microscope for proliferative changes. The biopsied tissue was also sent to endocrinology lab to find out how much progesterone and estradiol was taken up by the tissue.

Estradiol concentrations were 200 times greater as compared to the placebo tissues in women that used just the estradiol cream. Progesterone concentrations were 100 times greater in the biopsied tissue in woman that used the natural progesterone cream as compared to placebo. Estradiol increased cell proliferation by 230%. Progesterone decreased cell proliferation by more than 400%. Group C, the estradiol and natural progesterone group maintained the normal proliferation rate similar to placebo. Thus, this evidence supports that unopposed estradiol stimulation gives rise to proliferation of breast cancer cells. Natural progesterone transdermal application, opposes this estradiol stimulation.

Blood Testing Does NOT Work for Testing Transdermal Natural Progesterone

Blood testing of transdermal topical natural progesterone does not show a measurable rise of natural progesterone when progesterone cream is applied. This is because oil and water do not mix. Topical natural progesterone applied transdermally is not carried in the blood plasma or the water fraction of the blood. Topical natural progesterone is carried in the oil fraction of the blood. Transdermal natural progesterone is in the chylomicrons, the oil droplets in the blood, and the red blood cell membranes. Transdermal natural progesterone is NOT bound to a binding protein in the water fraction of the blood, initially. This is why many physicians believe that transdermal natural progesterone is not well absorbed in the body. They are monitoring the wrong test.  They should be using a saliva test to monitor the transdermal hormone application.[1]

Mothers and Babies are Exposed to High Levels of Natural Progesterone Naturally During Pregnancy

Thus, natural progesterone is fairly safe. Babies and mothers are exposed to high levels of natural progesterone, and mothers exposed to multiple high levels of progesterone during pregnancy carried to term have a smaller chance of breast cancer. This can be contrasted to a common pain reliever acetaminophen. Take half a bottle of acetaminophen, then you die from liver failure in two weeks and everyone gets to watch. Approximately, 100,000 Americans die from prescription drug overdoses every year. Prescription drugs and their combinations can be quite dangerous. Compared to prescription drugs and even over the counter drugs, Natural Progesterone is relatively safe.

1 out of 400 Allergic Reactions From The Cream Base, but NOT Natural Progesterone

I have never seen a severe toxicity from progesterone. There may have been an allergic reaction to one of the components of progesterone cream. There is, in my experience a one out of 400 chance that the patient will be allergic to some component of the progesterone cream, but not the progesterone itself.  One out of 400 patients have a rash when they use Progestelle.  In other words, if you just put on the cream base without the progesterone in it, one out of 400 people would have an allergic reaction to the base cream alone. In my experience, I've only had three in 25,000 patients that had a possible that allergic reaction to progesterone. However, it is important to remember that this is an allergic reaction, and not a toxicity reaction. I have never had a toxicity reaction progesterone that I have seen in the 25,000 patients that I have treated with progesterone since 1999 to 2015.

One bottle of progesterone contains 800 mg of natural progesterone. Suppose you pour the whole bottle of progesterone on yourself all in one sitting. Let's suppose a 50% absorption rate. This means you would get 400 mg natural progesterone. This is simply one day of third trimester pregnancy where your body produces 400 mg of natural progesterone per day. So natural progesterone is fairly safe.

The Most Common Adverse Reaction to Taking Natural Progesterone Can Be Avoided by Avoiding Xenoestrogens

The most common reactions I see are true in 40% of women taking Natural Progesterone without modifying their lifestyle is increased bloating, breast tenderness, headaches, pms, hair loss, and increased weight. This is because most, if not the vast majority of women in America are exposed to xenoestrogens in their environment.  Their soaps, laundry detergent, deodorant, lotions, cosmetics and toiletries contain chemicals that mimic estrogen, known as xenoestrogens.  The human body to protect itself shuts its own sensitivity down to estrogen when exposed to such a large load of xenoestrogens chronically.  This shutting down of sensitivity is known as "Down Regulation" in biology. 

When Natural Progesterone is taken, the estrogen receptors increase their sensitivity back up to normal.  Thus, taking Natural Progesterone for 40% of women that do not clean up their environment results in increased bloating, breast tenderness, increased weight, increased hair loss, and increased misery because the estrogen receptors have "woken up".

The solution to this problem is easy.  Simply avoid xenoestrogens for 1-3 months, then take Natural Progesterone.  Normally, topicals like lotions and cosmetics are absorbed transdermally into the fat, and it may take 1-3 months for them to wash out.  You can read more about Natural Progesterone side effects here.




1. John Lee, M.D. What Your Doctor May Not Tell You About Menopause. 1996, Time Warner book group, New York, New York, pages 228-239.