Today, confusion swirls about whether supplementing natural progesterone, a hormone made by women’s adrenal glands and ovaries, is safe.
Some of the confusion arises from incorrect interpretation and exaggeration of the original NIH Women’s Health Initiative (WHI) studies. In 2002, NIH abruptly and prematurely stopped the arm of the study in which women were taking Prempro® (Premarin/conjugated equine estrogens/CEE) and Provera® (medroxyprogesterone acetate/MPA) combined. Headlines read “Hormone replacement therapy associated with a 38% increase in stroke risk.”
But, there were many design flaws in the study and the results were misrepresented. That 38% was risk relative to the placebo group. The actual absolute increased risk of a single woman having a stroke increased from 2.4 women per 10,000 women taking placebo to 3.3 women per 10,000 taking Prempro. Real, but not nearly so scary. And yes, an increase from 2.4 to 3.8 is a 38% increase. But the absolute numbers for both are very small.
Even so, physicians told patients to stop HRT. and they did. Around 25% of postmenopausal women were on HRT at that time. This number dropped to 5%.
A belief arose in the lay public's mind that all hormone replacement therapy was dangerous.
However, only 8% of women doctors around the world stopped taking HRT after these headlines were published. 80% of lay users stopped HRT. Female physicians and wives of male physicians use HRT much more frequently and stay on it longer than laywomen.
Progesterone or Progestin?
Researchers call drugs with progesterone-like effects on the uterus progestins or progestogens. A second source of confusion about the safety and utility of progesterone is that progesterone, a naturally occurring female hormone, is almost always categorized with progestins. Most researchers hold the opinion that progesterone and progestins are biologically equivalent. They are considered to be identical and to act the same, but they are not and they do not.
Also, these drugs are then named “progesterone” in published literature. No wonder it’s confusing. A 2011 paper from China repeatedly uses the word progesterone when the study actually utilizes Provera. Researchers worldwide, the Mayo Clinic and journals all lump these drugs together with bio-identical progesterone.
So it’s easy to see why many doctors equate progestins and natural progesterone.
How is Progesterone Different from the Progestins?
Progesterone is a natural hormone. It cannot be patented. Progestins are patented drugs. That means drug companies can make money on them. The only company, Solvay based in Belgium, that did patent progesterone actually patented the delivery system, and not the hormone itself. Their product, Prometrium is not a drug at all. It is natural, bio-identical progesterone in peanut oil. It worked well.
Progestins are derived in a laboratory from natural progesterone or testosterone and—depending upon the origin of the progestin—they have different side effects. That is why women feel better on some birth control pills and worse on others. However none of the progestin drugs function like natural progesterone. All of them have the desired effect on the uterus. They make the uterus inhospitable to implantation of a fertilized egg. And when taken by post-menopausal women who are taking estrogen, progestins reduce the risk of uterine cancer. But in the rest of the body, the trillion plus cells that also have progesterone receptors do not respond to these drugs like they do to natural progesterone.
For example, the cardiovascular system responds one way to progesterone and another way to Provera. Researchers demonstrated this in 1995. The PEPI trial, Postmenopausal Estrogen/Progestin Interventions, measured blood tests of lipids and blood sugar predictive of cardiovascular disease. It compared the effects of Provera and bio-identical progesterone on these parameters. Women, who took Premarin, conjugated equine estrogen, alone or Premarin plus progesterone had significantly greater HDL (good cholesterol) increases than did those who took Premarin with Provera. So by raising HDL higher, progesterone lowers the risk of cardiovascular disease. Provera does not have this desirable effect.
Also screening tests for sugar control were worse for women on Provera. It accelerated the aging process by raising blood sugar. There was no increase in blood sugar levels in women on Premarin alone or on progesterone and Premarin. Bio-identical hormones work for us, not against us.
By 1997, there was no question that Provera was damaging to women’s cardiovascular system. But it is still widely used today, as are other progestins. These progestins are in birth control pills, patches, the vaginal ring and an IUD (Mirena). They are also in HRT patches and pills for treating postmenopausal symptoms. They are not identical to each other or to bio-identical progesterone.
Is there a need for progesterone replacement?
So when a woman’s trillion plus cells do not have sufficient progesterone, what symptoms appear? Dr. Thierry Hertoghe, a Belgian physician, wrote in his book, The Hormone Solution that common symptoms of progesterone deficiency are:
· large and increasingly painful breasts
· feelings of nervousness, agitation, and anxiety
· inability to sleep deeply
· feelings of restlessness
· swollen, tender or painful breasts before one’s period
· lower abdominal swelling before the period
· feelings of irritability and aggression
· “blowing up,” not having self-control
· heavy and painful periods
Most women’s progesterone levels start dropping in their late 30s, if not before. Typical early changes in the period are that it lengthens, and a woman will drip into her period and drip out of it, so instead of having a three-to-five day period, she has a seven-to-nine day period and she has increasingly severe PMS with tender breasts and new breast cysts.
A woman’s cycle moves through a constantly shifting balance between estrogen and progesterone. Up until ovulation, estrogen production increases. After ovulation, progesterone increases.
The ovaries are supposed to make adequate progesterone after ovulation. If they do not and the woman is estrogen dominant (too much estrogen relative to progesterone) prior to her period, she may be irritable, intolerant, very bright, very quick, and arrogant. If she has an adequate amount of progesterone, she can get a lot done during that two-week period because she is bright and smart, yet calm, secure and grounded.
Dr. Katharina Dalton, a British OB/GYN, first coined the term premenstrual syndrome in the 1950’s. She was adamant that the appropriate treatment for a hormone deficiency was to replace the hormone. She used only natural progesterone not the progestins.
Still menstruating women deficient in progesterone may develop PMS or fibrocystic breast disease early on. Over time these same women may develop uterine fibroids, breast cancer or uterine cancer—at least partially due to low progesterone. Estrogen levels may or may not be high. Certainly environmental estrogens exert an estrogenic effect in many people. All of this adds up to too much estrogen relative to its dance partner, progesterone.
If a woman has her ovaries removed she will need progesterone. If she has her uterus removed and keeps her ovaries, she will probably go through an early natural menopause and still need progesterone for the trillion plus cells in her body that rely on progesterone.
Bone health depends on both estrogen and progesterone. Estrogen slows down bone loss or resorption. It doesn’t build new bone. Progesterone and testosterone turn on bone building cells.
In healthy breasts, estrogen tells cells to multiply and divide. Progesterone scours the breast tissue and looks for cells that are “cancer wanna be cells” that will be stimulated by estrogen. Progesterone triggers apoptosis (aka programmed cell death) in these cells, so that these potential cancer cells commit suicide. Progesterone does not feed breast cancer cells.
Progesterone also slows down the tendency for breast cancer to metastasize. It has long been recognized that when women have breast biopsies on lumps that are later determined to be cancerous, they have a much lower risk of the cancer metastasizing to axillary lymph nodes when they are in their luteal phase, and progesterone levels are high.
In the brain, progesterone is a profoundly calming hormone--it actually calms the brain tissue and reduces inflammation. It reduces anxiety and agitation and it may even get rid of premenstrual or menstrual migraines, headaches and seizures.
Phyllis Bronson PhD in her book, Moods, Emotions, and Aging, also reports using progesterone to successfully treat women with chronic anxiety, PMS and premenstrual dysphoric disorder (PMDD). This is an illness in which women experience extreme depression and changes in mood prior to their periods. This is much more severe and disabling than PMS.
According to Bronson, the primary sex hormone is estradiol. But estradiol needs progesterone to balance it out and progesterone needs sufficient estradiol in order for it to do its job. They work together hand in hand. They are dance partners.
Estradiol clears the mental cobwebs that perimenopausal and menopausal woman may experience. It increases the brain connectivity and enhances memory tremendously. Progesterone, on the other hand, helps to calm the brain so that a woman is able to multitask and to focus on what she needs to do. She is not overwhelmed by worry and anxiety. Progesterone raises GABA (gamma amino butyric acid) which is the most calming neurotransmitter that people have. Women who need Xanax, Valium and alcohol to calm them down, may benefit from using progesterone instead. All of these raise or mimic GABA.
Progesterone replacement is not just about treating symptoms. It’s about preventing women from developing breast and other cancers later in life after decades of excessive estrogenic effect. Women who have moodiness as the primary symptom of PMS or PMDD, may need psychiatric medications, but they need progesterone first.
Lab Tests for Low Progesterone
There are many ways to determine if one has low progesterone. The most common way is to have blood work drawn on day #21 of a woman’s cycle where day one is the first day of the period. This level should be over 10 ng/ml. Optimally, it should be between 12 and 25ng/ml, but this number cannot be interpreted in isolation. Remember that estradiol and progesterone dance together. So, it has to be compared to the estradiol level. If a woman has and makes an excessive amount of estradiol, she may actually need an even higher amount of progesterone so that she is not estrogen dominant. Estrogen dominancy is dangerous for woman and can cause all the symptoms and diseases discussed above.
It is also possible to do salivary testing which is only reliable before going on hormones and a new urine test in which one collects four separate urine samples throughout the day. Formerly, one had to collect a 24-hour urine and this was decidedly cumbersome.
Physicians who are trained in their use can use all of these tests and each gives slightly different information that may be helpful.
Treatment for Low Progesterone
Over-the-counter creams are available and may help women who are just beginning to have progesterone deficiency; however, women who have serious progesterone deficiencies need to use compounded bio-identical progesterone or micronized progesterone in the form of pills, troches which dissolve in the mouth or prescribed creams. The dose will vary, but it will be significantly higher than what can be achieved with over-the-counter creams.
Sometimes the pills do not last 24 hours so it may be necessary to take these twice a day. Creams must be applied every 12 hours to have a uniform level. Premenopausal women who need progesterone should take it from the day after ovulation, until their period starts. This is usually days 15-28. Common dosing is 200-400mg a day.
Progesterone that is absorbed vaginally or through the skin is metabolized very differently than progesterone when it is swallowed. When swallowed, progesterone is converted into a very sedating compound that is helpful for women who have problems with sleep. If women find oral progesterone is too sedating, then topical progesterone will be a better choice.
Most post-menopausal women take progesterone daily. Doses vary from 50-200mg daily in divided doses. Dr. Thierry Hertoghe in Belgium and Dr. Jonathan Wright (the father of bio-identical homes in this country) both feel there is added benefit from cycling off and on progesterone to mimic nature earlier in life. However, the doses are not high enough to cause women to have a period. Having a period does not keep women from aging.
If one gets too much progesterone, women can experience a flattening of their moods. “It is like having a frontal lobotomy,” one physician described. Dr. John Lee, who brought awareness to the US of the role of progesterone in PMS, laughed that a woman with too much progesterone would not be upset if the tax collector was coming or if the house burned down. Think of a too laid back “whatever” attitude. If a woman takes even more progesterone, she can get depressed. Both of these side effects are easily treated by cutting back on the dose of progesterone.
Progesterone is also an upstream hormone in the adrenal glands, so it is possible for women to make too much cortisol from progesterone. In this case, the adrenal glands have to be balanced in conjunction with taking progesterone. A very few women have very unexpected reactions to progesterone. This is not a reason to use progestins. If this happens, they should consult their doctor. Not uncommonly, it is a sign that the woman has excessive yeast, according to Dr. Uzzi Reiss in his book, Natural Hormone Balance for Women.
Progesterone Really is Your Friend
Many women will still question whether progesterone is safe because conventional doctors assume that progesterone has the same negative effects as progestins did in the Women’s Health Initiative study. While the negative effects were overblown to the detriment of women’s health over the past decade, the study does not apply to bio-identical estrogen and progesterone. The study studied drugs, not our hormones designed over millennia by Mother Nature. The study showed that Prempro was unsafe.
There have been over 25 years and 100’s of studies on the safety of natural progesterone. There have been many physicians who have treated women with bio-identical hormones including estradiol and progesterone for the past 40 years. Those physicians like Dr. Dalton, Dr. Hertoghe, Dr. Wright, and Dr. Reiss, report substantially lower risk of breast cancer, heart disease, dementia, osteoporosis and an enhanced immune system. They have happier, calmer patients.
Women deserve natural life-affirming treatments for their hormonal imbalances. Progesterone is only one piece of a healthy life prescription. A healthy diet, exercise, stress management, restorative and uninterrupted sleep, supplements, detoxification and hormones as needed are all components of achieving and maintaining a healthy life as we age.