When the total truth came out about synthetic HRT (hormone replacement therapy) via the Women’s Health Initiative in 2002 and then in 2004 with the synthetic estrogen-only arm of the study, which was also ended because hormone replacement therapy (HRT) with conjugated equine (horse-derived) estrogen was found to increase the risk of stroke, the medical community went into turmoil and even divisiveness as to what should be recommended to women who present with symptoms of hormone imbalance. The report findings had an immediate impact on the millions of women using synthetic HRT and research reported that 50% of these users discontinued their personal use of synthetic HRT. Seemingly, both then and even now, millions of women are confused about what to believe is safe for relieving symptoms of fluctuating hormones while not causing more health concerns down the road.
Progesterone USP and the Endocrine System
First it is important that we distinguish between what progesterone does in the body as well as the definitions of natural progesterone and synthetic progestin.
What is progesterone? Progesterone is usually thought of as the hormone balancer, especially when it comes to the estrogens. Progesterone is a steroid hormone made by the corpus luteum of the ovary at ovulation, and in smaller amounts by the adrenal glands. It is the precursor, or substance from which most of the other steroid hormones are derived, including cortisol, androstenedione, the estrogens and testosterone. The jobs of progesterone run a gamut from normalizing blood sugar levels and facilitating thyroid hormone action to regulating menstrual cycles and maintaining a healthy pregnancy. While estrogen levels rise during the first half of the menstrual cycle, progesterone levels rise in the middle of the menstrual cycle. Progesterone’s most important jobs in menstruating women are two-fold: 1) it prepares the uterus for implantation with a healthy fertilized egg, and 2) it supports the early stage of pregnancy. If there is no implantation, progesterone levels will drop until another menstrual cycle begins.
Studies show that progesterone has anti-proliferative effects on breast cancer and leukemia cells (Formby 1998; Hayden 2009; Hilton 2010). Breast cancer is 5.4 times more common in pre-menopausal women with low progesterone levels than with favorable levels (Cowan 1981). Other data suggests that while bioidentical (natural) progesterone does not increase the risk of breast cancer, synthetic progestins used in conventional HRT (Hormone Replacement Therapy) do (Campagnoli 2005). Natural (bioidentical) progesterone has also been found to have neuroprotective properties. One study called for more attention to progesterone as a “potent neurotrophic agent that may play an important role in reducing or preventing motor, cognitive, and sensory impairments [in both men and women]” (Stein 2005).
What Is Natural Progesterone? Bioidentical natural progesterone is made in the body or made (not extracted) in the laboratory from either soybeans or the Mexican wild yam (Dioscorea villosa). The process was discovered in the 1930s by Pennsylvania State University professor Russell Marker, who transformed diosgenin from wild yams into natural progesterone.56 Natural progesterone refers to bioidentical hormone products that have a molecular structure identical to the hormones our bodies manufacture naturally. One of the most effective forms of bioidentical progesterone is called micronized progesterone. The process of micronization allows for steady and even absorption of the medication. Accordingly, both the micronized progesterone and other commercially available progesterone creams contain bioidentical progesterone. (1)
What Are Synthetic Progestins? Unlike natural progesterone, non-bioidentical synthetic progestins are not molecularly identical to the hormones found naturally in the body. Synthetic progestins were first developed for use as contraceptive agents. Because the half-life of natural progesterone is very short, researchers sought an agent that would produce longer-lasting, more potent effects than natural progesterone. Birth control pills usually contain a synthetic progestin and a synthetic estrogen. Synthetic progestins are very potent, with just a small dose preventing ovulation and thus functioning as birth control. A slight change in the chemical structure of progesterone has allowed pharmaceutical companies to create patentable and highly profitable birth control products. (1)
One of the most common progestins, medroxyprogesterone acetate (Provera®), has been linked to blood clots, fluid retention, acne, rashes, weight gain, depression, certain cancers, and other disorders. Non-bioidentical progestins are also able to bind to glucocorticoid, androgen, and mineralocorticoid receptors, which may explain the wide range of adverse side effects many women experience while taking synthetic progestins.60,61 The vast majority of research studies have been conducted using progestins rather than natural progesterone, which helps explain the disparity and negativity of the results. (1)
The FDA has also approved a drug called Prometrium®, an oral pill containing 200 mg of natural micronized progesterone taken daily. Because orally administered progesterone is metabolized by the liver, it may be contraindicated in patients with certain liver conditions. Initial liver metabolism of progesterone (called “first-pass” metabolism) also creates higher levels of certain metabolites of progesterone than transdermal or transmucosally administered progesterone. (1)
Experience tells us that when the endocrine system is in balance, a woman’s overall health, mood and sense of well-being is maximized. Natural progesterone USP cream, when used correctly, seems to help many women through the often unbearable symptoms of peri-menopause, menopause and hormone imbalance while providing many extra health benefits. Having the same molecular structure as the natural progesterone produced by the body, progesterone USP cream is absorbed through the skin and directly into the bloodstream and, unlike oral progesterone, by-passes filtering by the liver. (1)
As beneficial as natural progesterone USP cream is for many women, we must be aware that we are dealing with a very delicate system – the endocrine system – which has an effect on just about the entire body.
During the peri-menopausal years, it is progesterone, not estrogen like many believe, that is the first hormone to decline. The total amount of progesterone produced in the body declines to less than one percent of the normal, healthy level. This drop could be from low levels of dietary zinc, magnesium deficiency, Vitamin B-6 deficiency or too many prescription meds such as anti-depressants. All of these can cause chaos on healthy progesterone levels. However, lifestyle choices seem to be the most important factors in causing estrogen and progesterone imbalance. Some of the symptoms from declining progesterone levels are mood swings, insomnia, depression, weight gain, hot flashes, fuzzy thinking, PMS and irritability.
When using any type of HRT, it is important to do your own research and determine fact from fiction.
Four head-to-head studies comparing progesterone to non-bioidentical synthetic progestogen (progestin) reported that women experienced greater satisfaction, improved quality of life, and fewer side effects when switched from progestin to progesterone (Hargrove 1989; Montplaisir 2001; Ryan 2001; Lindenfeld 2002). The beneficial effects of progesterone compared to non-bioidentical progestin included a 30% reduction in sleep problems, 50% reduction in anxiety, 60% reduction in depression, 25% reduction in menstrual bleeding, 40% reduction in cognitive difficulties, and 30% improvement in sexual function. Eighty percent of women in the study reported overall satisfaction with the bioidentical progesterone formulation (Fitzpatrick 2000).
Does the Body Store Progesterone USP?
Several years ago a “theory” about progesterone USP cream and how it is used by the body was posted in an online article that basically stated: “… progesterone is highly fat soluble and once applied to the skin will store itself in a woman’s fat tissue. When one first uses the cream, there is no problem here as the fat stores are very low. But as time goes on, the cream accumulates and contributes to disruptions in the adrenal hormones such as DHEA, cortisol, and testosterone.” Of course, many grabbed this theory and it spread like wildfire among women and practitoners causing many to question the use of progesterone USP.
What are the facts? Progesterone USP is extremely lipophilic, more so than any of the other steroid hormones. As such, the majority of a good progesterone cream is quickly and thoroughly absorbed into the skin, almost regardless of the carrier (note: there seem to be better carriers than others). Progesterone USP should always be used cautiously and, in fact, I always recommend saliva testing one’s hormones BEFORE using any type of HRT.
The theory that, in females, natural progesterone is absorbed by fat and released as needed has no proof. However, there is ample evidence that virtually all of a dose of transdermal progesterone cream is absorbed rapidly into the bloodstream and thus is not stored. It is important to understand that using correct application sites (as well as rotating application sites) are extremely important and can determine whether or not progesterone cream will be effectively utilized by the body. Of course, if one rubbed progesterone cream on the buttocks (which is not a recommended application site) every day, there is obviously a chance some of it could be held in fat. Progesterone USP should always be applied to thin skin areas where blood vessels can be seen such as the inner arms, hands, neck, chest, back of knees, top and bottom of feet. If the progesterone cream is pH balanced, it can be applied around the vaginal area (called trans-mucosal application) and many women report they seem to get effective results with lesser amounts of cream when used in this manner. It is important to note that one can have access to the best formulated progesterone USP cream available, but if one does not know or understand how to use natural progesterone USP correctly, most likely maximum benefits will not be fully achieved.
Using Progesterone UPS
Before recommending progesterone USP, knowledgeable practitioners will recommend that one’s hormone levels are tested through saliva in order to establish the actual need for hormone therapy and to provide a baseline for future testing. Many practitioners do not convey the importance of saliva testing hormone levels before using any type of hormone therapy. And unfortunately, some practitioners are not educating women about the difference between saliva testing and serum testing as well as why saliva testing is usually more reliable in establishing the need for HRT.
Although the overuse of progesterone USP is not something that will usually cause harm, the solution that we are after is achieving balance. High levels of progesterone showing up on saliva tests almost always indicates contamination of the test (example — one has applied progesterone and then touched their lips or even the top of the testing vial with the hand used to apply the progesterone, etc.), one is using a progesterone dose that is much too high for their physiological need or one is using progesterone and didn’t indicate this on the test questions.
Progesterone USP should be used in a physiological dose, measured out correctly for each application and applied correctly making sure that application sites are rotated with each use. Trying to “eye” the application amount usually ends up in applying more or less than is actually needed. This can cause a roller coaster effect on one’s hormones. To maintain a stable hormonal level one should use progesterone cream in doses according to nature and cyclic events as nature intended. This will ensure that one always has sufficient amounts of progesterone in the body. Of course, there are certain things that cannot be fully controlled such as the impact of our environment. We can, however, control the dose and application of progesterone USP by being consistent. Stopping and starting, or random use is not conducive toward hormonal balance, will confuse the body, and may make one feel less than their best. Thus consistency and compliance is mandatory when using progesterone USP. For most women it can take from three to six months or more for full symptom relief to occur.
Progesterone USP – Hormone Symptom Rescuer?
Natural progesterone USP is often advertised as being able to resolve all women’s hormone symptoms. However, hormone balance is not only about adding more progesterone USP and more estrogen. Instead, it is about achieving and maintaining an effective ratio balance between estrogen and progesterone, just as nature intended for your body. If your body is already experiencing high estrogen levels then you will need to address the estrogen dominance separately to the issue of progesterone deficiency. In many cases, women are ovulating and producing very normal physiological progesterone levels that would definitely be enough to keep them well and balanced, if they weren’t estrogen dominant. So simply adding more progesterone cream may sometimes be a cop-out for taking some personal and total responsibility in lifestyle changes that will further aid the body towards hormone wellness and balance.
Like most things in life, we must always use caution. There is no one magic bullet when it comes to getting the endocrine system balanced and healthy. Natural progesterone USP is one of the safest ways to assist women with the bothersome symptoms of hormone imbalance especially when combined with a whole body balancing program.
In closing, the following table shows the benefits of natural progesterone compared to estrogen. As you can see, the effects of progesterone USP are many—we would do well to use it wisely. One thing to remember is that if your healthcare practitioner recommends the use of any type of estrogen*, it should always be balanced with progesterone USP.
Progesterone USP Effects
Stimulates breasts cysts
Protects against breast cysts
Increases body fat storage
Helps use fat for energy and keep it off hips
Salt and fluid retention
Natural diuretic (water pill)
Depression and headaches
Interferes with thyroid hormone
Facilitates thyroid hormone action
Increases blood clotting and risk of stroke
Normalizes blood clotting
Decreases libido (sex drive)
Impairs blood sugar control
Normalizes blood sugar levels
Loss of zinc and retention of copper
Normalizes zinc and copper levels
Reduced oxygen level in all cells
Restores proper cell oxygen levels
Increased risk of endometrial cancer
Prevents endometrial cancer
Increased risk of breast cancer
Helps prevent breast cancer
Helps decrease bone loss slightly
Increases bone building
*A new study published in JAMA Internal Medicine 2013 links conjugated equine estrogen hormone therapy — estrogen derived from the urine of pregnant horses — to a woman’s risk of developing heart disease. The study involved 384 women who were postmenopausal and taking hormone replacement therapy, HRT. The women were ages 30 to 79. This risk of taking conjugated equine estrogens was compared to the risks of a second type of hormone therapy, estradiol which is a natural estrogen. Women who used the estrogens that came from horse urine — also known as Premarin — were twice as likely to have venous thrombosis. The women taking conjugated equine estrogen were also slightly more likely to have heart attacks, but risk of stroke did not vary based on which medication was taken.
1) Report. Bioidentical Hormones: Why Are They Still Controversial? Life Extension Magazine October 2009