What You Need To Know About Progesterone USP

What You Need To Know About Progesterone USP

October 16th, 2013 by Loretta Lanphier

What You Need To Know About Progesterone USP

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.

Relalted: Endocrine Disrupting Chemicals – What You Need to Know

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.

Estrogen Effects

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

Natural anti-depressant

Interferes with thyroid hormone

Facilitates thyroid hormone action

Increases blood clotting and risk of stroke

Normalizes blood clotting

Decreases libido (sex drive)

Increases libido

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

Loretta Lanphier is a Naturopathic Practitioner (Traditional), Certified Clinical Nutritionist, Holistic Health Practitioner and Certified Clinical Herbalist as well as the CEO / Founder of Oasis Advanced Wellness in The Woodlands TX. She has studied and performed extensive research in health science, natural hormone balancing, anti-aging techniques, nutrition, natural medicine, weight loss, herbal remedies, non-toxic cancer support and is actively involved in researching new natural health protocols and products.  A 14 year stage 3 colon cancer survivor, Loretta is able to relate to both-sides-of-the-health-coin as patient and practitioner when it comes to health and wellness. “My passion is counseling others about what it takes to keep the whole body healthy using natural and non-toxic methods.” Read Loretta’s health testimony Cancer: The Path to Healing. Loretta is Contributor and Editor of the worldwide E-newsletter Advanced Health & Wellness. Check out Oasis Advanced Wellness and our natural skin care site Oasis Serene Botanicals.







  • Alfred Blue

    Your article is about women, but don’t men need progesterone, too?

    Alfred Blue

  • I get migraines, that are related to my cycle. I get them at the end and after my cycle ends. I have been using a Progesterone Cream and it doesn’t help. Do you know, is it because my levels are to low or too high? I think I need to check into the saliva testing.

    • Hi Monica – I suggest having one’s sex hormone levels checked by saliva testing before beginning any type of hormone therapy. However, if one is already using hormone therapy, saliva testing can still be done.

  • I see there is also a liquid version of Progesterone that is taken sublingually. Apparently this is the version that Kalish recommends. Is there a USP certification for the liquid version, or only the micronized cream version? Do you have any information on the efficacy of this form of Progesterone? Thank you.

    • Sublingual progesterone has been available for many years usually as a troche and currently as a liquid sublingual. As far as the progesterone being USP certified, that is a question that you should ask Kalish. Be aware that with the sublingual dosing of any type it is likely that one will be swallowing a majority of it. It was once thought that 80 percent was metabolized with first-pass, but it is now known that 80+% is actually metabolized in the gut to the neurosteroid allopregnanolone which is a potent sedative via the GABAA receptor, with an additional amount of metabolism occurring in the liver. This leaves virtually little to no active progesterone to work as progesterone in the system. Sublingual progesterone tends to only last in the system for only 4 to 6 hours. Because the mucous membranes of the mouth absorb so efficiently and effectively, this delivery system tends to create a steep rise in progesterone, followed by a steep drop—not the best way to achieve hormone balance. Be sure to check ingredients as some have ingredients that in my opinion are harmful.

      • Carol

        Thank you Loretta… sorry for the delay, but thanks very much for this information. I think I will go the cream vaginal application route.

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  • Connie Rossi

    I have been getting a lot of uti’s. Is this common in post menopausal women? I don’t want to keep taking antibiotics. Will the bioidentical progesterone help me? Had a cystoscopy, tested normal. Very fustrated.

    • Unfortunately, urinary tract infection is the most common bacterial infection in women in general and in postmenopausal women in particular. Post-menopause is a season of life characterized by a significant reduction in ovary estrogen secretion, which is often associated with vaginal atrophy. Clinically, it manifests as a syndrome characterized by vaginal dryness, itching, dyspareunia, and urinary incontinence which may sometimes imitate a UTI (LoE 2a) [15,16]. There is research that indicates estrogen stimulates the proliferation of lactobacillus in the vaginal epithelium, reduces pH, and avoids vaginal colonization of Enterobacteriaceae, which are the main pathogens of the urinary tract. However, there is other research that indicates adding estrogen to reduce the occurrence of UTI’s is not as effective as once thought.

      Bioidentical progesterone plays an important role in the prevention of vaginal and urinary tract infections. Estrogen and progesterone are a “pigeon pair” and bioidentical estrogen should never be given|used without including bioidentical progesterone. Estrogen is necessary for cells to make progesterone receptors, and progesterone helps make estrogen receptors more sensitive. When progesterone is low (as is usually the case in post-menopause), estrogen receptor sites become less sensitive to estrogen. The result is that many women with sufficient estrogen will nevertheless have signs of estrogen deficiency, such as vaginal dryness and hot flashes, as well as estrogen dominance symptoms. (These symptoms are why estrogen is usually recommended by doctors.) When progesterone is restored to normal physiological levels, estrogen receptors become more sensitive and signs of estrogen deficiency disappear: hot flashes diminish in intensity and frequency, vaginal lubrication returns, and urinary tract concerns go away. Remember that progesterone is also part of our immune defense system that prevents infections: progesterone aids in the formation of secretory IgA, an immune globulin that traps germs before they enter mucosal tissues such as those found in the vagina. This is why many women who begin using progesterone cream find that their allergies and sinusitis clear up. Therefore, whenever estrogen is given, or progesterone is deficient, it is wise to supplement with normal physiological doses of progesterone to optimize one’s immune defenses. I highly suggest performing a saliva test of your sex hormones before using any type of bioidentical hormone replacement therapy (BHRT) to establish need as well as a baseline.

      Other alternative methods for prevention of UTIs that you may want to research include taking a good probiotic that includes lactobacilli; d-Mannose; cranberry extract in capsule form; colloidal silver; herb uva ursi.

  • cheryl

    Is Progesterone USP (what does the USP stand for any way)., the same as micronized p;rogesterone? What is tthe best way to take Micronized progesterone….I tried this orally once for about 8 days and got the worst Heart burn symptoms ever (which almost a year later still as some residual effects.)

    • USP stands for United States Pharmacopeia. The USP is an independent, not-for-profit organization who sets all of the quality standards for prescription and over-the-counter (OTC) medications as well as other healthcare products manufactured or sold in the Unites States. In my experience, using a transdermal cream containing at least 20-35mg of USP progesterone per 1/4 teaspoon is best for most women. There really is no one-size fits all when we talk about bioidentical hormones. Make sure that the base cream does not contain toxic ingredients. I recommend and use with clients Oasis Serene. The main reason that I recommend transdermal progesterone cream over oral progesterone is because some 80% to 90% (depending upon the person) of the oral dose is lost through the filtering of the liver. At least 200 to 400 mg daily is needed orally to achieve a physiologic dose of 15 to 24 mg daily. These high doses create undesirable metabolites and unnecessarily overload the liver. Micronized progesterone is used in capsules and can also be used in transdermal creams. Progesterone is considered USP if it fits the quality standards set up by the USP.

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