Avoiding Problems with Progesterone

Article by Dr. Michael Borkin, N.M.D.
Alternative Medicine Magazine - September 1999

Natural progesterone cream has many advantages over conventional estrogen-based Hormone Replacement Therapy in maintaining womens' health, but it is crucial to use the right product in the right way. Here is everything women of all ages need to know.

One out of two women in the United States under the age of fifty suffers from Premenstrual Syndrome (PMS); of the women over fifty, 60%-80% will suffer from symptoms associated with menopause. Approximately one percent of all U.S. women will have a hysterectomy, an in most cases this procedure should not have been performed. The unfortunate part of this is that, in the great majority, the symptoms, and potentially life-threatening problems, associated with hormonal dysfunction can be avoided. In most cases the problem is one of mismanagement. Most women have been led to believe that their options regarding their sexual health are limited, and in too many cases the medical community is not willing to inform them of options outside the conventional approaches. The fact is that most physicians don't utilize the diagnostic tools available, or don't have the experience necessary to properly treat or even determine all the alternatives. Instead, the pharmaceutical companies have controlled the flow of knowledge, and most doctors have been indoctrinated into believing that synthetic hormones and surgery are the only options.

In 1994 the New England Journal of Medicine published a study involving 121,000 women using traditional hormonal replacement (HRT) therapy. The study revealed that the use of synthetic hormones (estrogens and progestins) increased the likelihood of developing breast, ovarian, and uterine cancer by up to 40%. Several studies since have confirmed this and the response by the pharmaceutical industry was the introduction of estrogen blockers, such as Tamoxifen. Today, synthetic estrogen is the primary hormone used to treat PMS and menopausal complaints. Many of the complaints are actually exacerbated by this approach. Depression, blood sugar problems, edema, weight problems, headaches, loss of libido, fibroids, osteoporosis, and even digestive problems can be side effects of estrogen replacement.

One attempt to counter these side effects has been the use of synthetic hormones called progestins. Progestins, although similar to Progesterone, are not Progesterone. Unfortunately, this only complicates the situation. Because progestins are not Progesterone, they can cause numerous side effects such as depression, water retention, headaches, breast tenderness, skin problems, insomnia, liver problems, and increased risk of birth defects.

WILD YAM & Progesterone CREAMS Many women have chosen to circumvent much of the medical experimentation they have encountered and avoid the concomitant side effects by turning to the alternatives of wild yam cream and natural Progesterone cream. Wild yam and Progesterone creams have been available without prescription for many years. What makes them especially interesting is that in most cases they work - at least for a while. The fact is that when used properly these products can be extremely beneficial. The key to that statement is when used properly. It is important to realize what these products can do and how to get the most use out of them. I have used many topical/transdermal (applied through the skin) hormones in my practice over the years, and have learned the secrets that make them work.

I was first introduced to wild yam cream in 1984. I expected a pill, but to my surprise it was a jar of cream. It was explained that a topical application avoided many of the pitfalls of the oral route; it increased absorption and utilization dramatically. One of the major obstacles of hormone supplementation is the gastrointestinal tract. If digestion is impaired, then there is little chance that any form of oral supplementation would ever work.

Hormonal Relationships

This "miracle cream" contained a root extract from "wild yam," which contained steroid-like structures that mimic hormones produced by humans. There are more than eighty varieties of wild yams grown around the world, but only a few have medicinal qualities. Four are native to North America, and only one, the Mexican variety, is commonly used for medicinal purposes, since it contains high levels of active substances called "sapogenins."

A biochemist I knew, who worked with exotic herbs, explained to me that the active ingredient found in Mexican wild yam was called "diosgenin" which had been studied for years. Diosgenin was found to act as an estrogen antagonist, with estrogen capabilities similar to that of the genistein in soy. It has the ability to help normalize the ratios of estrogen to Progesterone. The reason for this was theorized to be the result of the conversion of diosgenin to Progesterone. But this pathway takes so many steps, that, while this is routinely accomplished in a laboratory, it seemed impossible for this to actually occur in the human body.

Diosgenin and soy are used as raw materials for the synthesis of pharmaceutical-grade Progesterone. Naturally derived Progesterone is exactly the same as that which is produced by the body. You need to use pure pharmaceutical-grade compounds to raise Progesterone, DHEA, or other hormone levels, because you can't get "conversion" from wild yam diosgenin. Medicinal wild yam-based products containing sufficient diosgenin content do exhibit estrogenic biological activity, but not because they can be converted to hormones; they do so because they mimic hormones in-vivo (in living tissue).

It does not matter whether or not diosgenin (the active sapogenin in Mexican wild yam) converts to any sex hormones in the body. There is still cellular activity from the almost identical steroid structure of the diosgenin molecule. Clearly, there is a relationship between the structure of the phytohormones (diosgenin from Mexican wild yam, and genistein from soy) and the naturally occurring sex hormone estradiol (E2). This more than likely explains why wild yam creams can have such a positive effect on some women even when used without Progesterone. The delicate chemistry of the female reproductive system responds not only to changes in hormonal levels, it also responds to changes in the ratio of one hormone to another. In the case of estrogen and Progesterone, this ratio shifts back and forth throughout the menstrual cycle. During the first 14 days estrogen is the dominant sex hormone. This dominance shifts during the last 14 days of the cycle to Progesterone. Wild yam may help by displacing estrogen and reversing estrogen dominance, in cases where estrogen remains high during the second half of the cycle.

Wild yam creams are also helpful to pregnant women in relieving many symptoms of morning sickness, including nausea and inflammation. It may also help prevent miscarriage, and has shown to help relieve discomfort after childbirth. Wild yam is a powerful antispasmodic and has been used for cramps, stress, and menstrual pain. It has even been used as a natural contraceptive. Taken in large doses over a long period of time it causes a temporary sterility. (This is reversed once the wild yam is discontinued and it clears the body.)

Recent studies have shown diosgenin to have anti-cancer activity in animals. It also can be used orally to sooth the inflamed tissues of the stomach and intestines and help mitigate such conditions as adult colic, celiac disease, colitis, and diverticulitis.

I was amazed at all I was learning, because this seemed to have the potential to solve a major problem that I, and the rest of the healthcare community, confronted daily. Stated simply, this was how to in?corporate hormonal replacement therapy into a responsible program and avoid causing new and potentially severe problems.

Progesterone Supplementation

I began to experiment with wild yam cream, and with much optimism gave it to my female patients who were suffering from PMS or the symptoms of menopause. The results were mixed; some women reported incredibly positive changes, while others continued to suffer. I began to realize that wild yam was only part of the answer to affecting the origin of these symptoms. I continued to try different forms of wild yam and found that the original formula of ProGest, and Alvin Last's Wild Yam Cream, to be extremely consistent over the years. Many women responded without the need for additional hormones, but wild yam wasn't the panacea I had hoped it would be. At this point it became obvious that if your intent is to affect Progesterone levels, then you have to use a Progesterone hormone. My attention shifted to natural Progesterone as a possible answer to the percentage of women that didn't respond to wild yam.

To better understand why supplementation is sometimes necessary, and why timing of the use of Progesterone is crucial, you need to review the basic events in which Progesterone plays a role. In women, Progesterone's first action is to prepare the uterus for pregnancy, hence the name which comes from the Latin "progestin" meaning "before pregnancy." During pregnancy, research indicates that Progesterone levels have a major impact on the rate of fetal development, especially neurological development, as well as increasing birth weight.

This is just one of many roles it plays in fetal health and development.

Because of Progesterone's effects on the utilization of thyroid hormones, maintenance of weight, skin (acne), and energy are also cross-linked to Progesterone levels.

Progesterone's Unique Qualities

Progesterone is a structural hormone that can change its form to become other hormones. Because of this unique quality it can be converted and utilized by the body to the point of depletion. This is due primarily to stress. One of Progesterone's major capabilities is to convert to the adrenal stress hormone called cortisol. This is the reason many young girls and professional athletes suffer from amenorrhia, or other menstrual problems. They produce enough Progesterone, but they convert it into a stress hormone, depleting the Progesterone and causing a multitude of problems.

In addition, Progesterone helps to prevent estrogen from interfering with its function. When estrogen levels become too high, estrogen can prevent (the thyroid hormone) from being utilized by the target tissue. Many times, low values of the thyroid hormones T3 and T4 are normal but, because of too much estrogen, the thyroid hormone is unable to perform its function.

Progesterone is unique in that it acts as precursor to most steroid functions (except those of estrogen and testosterone) which help regulate blood sugar elevation and proper nerve conduction.

The most unique aspect of Progesterone is its anti-estrogenic capabilities. Estrogen plays a very broad physiological role in both women and men. Estrogen affects every system in the body to some extent. Its role in affecting reproduction and sexual health is one of the most important. In this case, Progesterone works in ratio to estrogen, and it is this ratio that remains important even if either hormone level is suppressed. As I stated before, it is not always the level of a hormone that can cause a problem, it may be its relationship to other factors. This is the reason that sometimes a hormone can be in "normal range" but can, in fact, still cause a serious problem. Hormone levels are difficult to interpret because much of the hormone found in the blood is bound to other proteins and unable to be utilized. Only free fractions (unattached hormones) can be utilized. These free fractions can be accurately assessed using blood or a "Timed Hormonal Capture," using saliva as a testing medium (I prefer to use saliva testing to determine the exact free levels and ratios of Progesterone, estrogen, testosterone, and the stress hormones cortisol and DHEA.

Monitoring Progesterone's Use

I was first exposed to saliva testing in 1994, and began to monitor my patients by establishing a baseline before beginning Progesterone supplementation and then monitored the levels periodically while they were on the supplement therapy. At first the numbers were very impressive. Within weeks, sometimes even hours, patients began noticing a positive effect. The Progesterone values soared, and I felt I had my female patient's hormonal problems under control. Then one day I received a call from a medical doctor treating one of my former patients who had moved out of state. The doctor was unfamiliar with natural hormonal supplementation and was upset when he learned that the patient had not used traditional Hormone Replacement Therapy (HRT) to treat menopause. The patient had instead used nutritional supplementation, experienced none of the usual symptoms of menopause, and had had no problems for several years up until then. The doctor had taken a blood sample and an extremely high Progesterone level was shown. The only explanation was the Progesterone cream she had been using. A saliva test two weeks later confirmed extremely high Progesterone levels, but, when asked, she stated she hadn't used her Progesterone cream for more than a month. I consulted with the laboratory medical director that had performed the saliva test and was told that these high levels were among women using Progesterone creams. The problem is that most creams are not formulated for proper take up and clearance (i.e., how it is absorbed and fully utilized). Because they make no drug claims, little data is available as to their effectiveness and safety.

There are hundreds of Progesterone yam creams available. The amount of Progesterone present in these creams, as well as other active ingredients, delivery methods, and price varies from brand to brand. These factors are important, because without the addition of the proper cofactors - nutrients necessary for Progesterone to work properly ? such as vitamins A, D3, B5, and 6, the resultant cream will be of little value to the user. These nutrients (either included or supplemented) are paramount. There is also a synergy of the entire formula that is required in order to achieve the desired results.

Since Progesterone has no known side effects except for its obvious impact on menstruation, and producing a mild euphoria, one cannot overdose, so the standard approach to supplementation is to: (1) to use it in sufficient quantity to make the symptoms disappear, and (2) to time its use so it doesn't interfere with the normal shifts during the menstrual cycle. Symptoms of PMS are most common around ovulation and during the premenstrual week.

Metabolic Clearance

The primary problem with Progesterone is not dosage, but metabolic clearance. If, due to uncontrolled prescriptions or imperfect formulation, the Progesterone is not properly absorbed and fully utilized, the initial problems will remain, and possibly additional problems created, such as depression, headaches, hypoglycermia, and vertigo. In order for the Progesterone to be effective it must be given in a manner that mimics the body's own delivery. This means that it is important to give the correct dosage, at the right times.

This (delivery and dosage) can be accomplished a few ways: orally, sublingually (under the tongue), via vaginal suppositories, injected, pellet implant, or applied topically (where it is absorbed through the skin). The method of delivery has an immense influence on the rate of absorption. An oral dose is dependent on several factors, including digestion. Once absorbed through the gut, the dose goes on to the liver for uptake (metabolism). Uptake through the liver is known as "First Pass." With Progesterone, only about 5% of the dose will be absorbed through the liver. if the liver is congested or diseased, it will interfere with this absorption.

Sublingual products yield as much as 90 % absorption, but are available only by prescription, and are not always easy to find. Injectables yield high absorption, but poor compliance because most people would rather not inject themselves. Vaginal suppositories are an effective means of supplying Progesterone directly to the tissues involved, but are also available only by prescription. Implanted pellets work well, but cannot be controlled. Once implanted, pellets continue to release Progesterone for up to three months, but don't allow the natural shifts from estrogen to Progesterone. Transdermals, on the other hand, are easy to use, and yield absorption levels that range between that of sublinguals and injectables. At this high rate of absorption, less stress placed on the patient, and compliance is usually very good.

I have found that the most effective type of delivery for this application is known as a Transdermal Liposome Delivery System (TLDS). Liposomes are microscopic lipid (water-insoluble fat) globules that are made of a natural material similar to that of the cell membrane. This allows them to easily pass into the target cell and deposit their payload. When applied to the skin, they penetrate quickly through the tissue, are picked up by the capillaries, and are transported through the bloodstream to where they are needed. The liposomes are filled with Progesterone or whatever nutrient is desired. The advantage to this form of delivery is that it is predictable. The time it takes to pass into the cells and be utilized - its clearance - is easily calculated.

Most of the Progesterone creams available today use an inexpensive oil (fat-soluble) cosmetic base, rather than the more expensive liposomal compound. This can be a problem - the oil?based compounds have a tendency to stay in the skin for a long time, releasing their payload for an extended and unpredictable period of time. For instance, during the period of menses (first six days of menstrual cycle), Progesterone should be discontinued because it can interfere with the normal shift from Progesterone to estrogen dominance. But in a simple oil-based formula, the levels can remain high, due to the ongoing release into the bloodstream.

I have seen as many problems created as resolved in oil-based formulas because of this uncontrolled method of delivery. A typical scenario would be as follows: After the first week or two of using Progesterone cream, there is a noticeable change as Progesterone levels normalize. It continues for six to eight weeks, during which the levels continue to go higher and higher. Now instead of having a long menstrual cycle (29 to 40 days), the cycle becomes shorter (14 to 27 days). The positive feelings that were first experienced begin to fade and are replaced with new symptoms. Many times I have had a patient discontinue use of Progesterone cream and still found high levels three or four months later. I recommend a liposomal cream to my patients. These creams have a relatively short clearance time. In addition they contain pregnenolone. Pregnenolone is the precursor to all of the steroid hormones (those made by the ovaries, testicles, and adrenal glands), including Progesterone, estrogen, testosterone, the cortisol and DHEA (dehydroepiandrosterone). The pregnenolone acts like a reserve; if Progesterone is depleted, the pregnenolone can be utilized and converted into it. These creams also contain synergistic combination of needed nutrients, and botanicals that supply the necessary foundation for these to function properly. Sabre Sciences [and Aarisse Health Care] custom formulate these sophisticated liposome creams. They formulate the cream based on the information given in the findings of the 24-hour Timed Hormone test. This takes the guesswork out of designing a successful protocol, and produces a cream designed specifically for your hormonal profile.

Dosages: What's Right For You

Once you find a product that satisfies the requirements of potency, co-factors, and delivery, what is the proper way to use it? Dosages vary greatly from person to person. We are as different as our fingerprints, and since age, weight, and sensitivity vary greatly, so does the amount necessary to have the desired effects. The basic approach to dosage is simple - use however much it takes to stop the symptoms. This doesn't mean to start out taking the entire jar. It is best to start with a low dose and increase dose until you get the desired results. I recommend to my patients to start with 1/4 tsp. once daily and to increase the dose a 1/4 tsp. each day until the symptoms begin to lessen. Once symptoms are under control, maintain this dose for 60 days (2 complete cycles), then begin to decrease the dose little by until you find the amount that is right for you. Premenopausal women should only use the cream from day 7 of their cycle (day one is the first day of menses) and continue until day 28. Postmenopausal women may create a cycle by using the cream for three weeks and resting one week each month. If menopausal symptoms and/or hot flashes persist, continue using the cream up to 90 days or until the symptoms stop, then cycle for 3 weeks on and 1 week off.

The use of natural Progesterone or any type of hormone therapy should always be under the guidance of a healthcare practitioner. Although no side effects or toxicity have ever been reported from high doses, it is possible to upset the proper ratios necessary for Progesterone and its related hormones to function properly. A missed period is usually an indicator that you are using Progesterone incorrectly.

Progesterone may not be the answer for everyone, but it certainly something to consider. If you find after a few months of using a cream that it hasn't had (or no longer has) positive effects, discontinue it, and consult a knowledgeable healthcare professional. Many times other problems, such as thyroid dysfunction, liver disease, gastrointestinal dysfunctions, heart disease, or cancer, can play a role, interfering with the cream's efficacy. The main thing to remember is that Progesterone creams can differ radically in how they are formulated. Ask your doctor, or healthcare professional, to help monitor your hormonal levels, and make sure that the manufacturer of your Progesterone cream has supplied you or your doctor with a complete ingredient list and clearance data. If you don't have a doctor, some labs offer tests directly to the public (see below). Always establish a need for supplementation before wasting time and money, and possibly affecting your health negatively.

Natural VS. Synthetic Hormones

Synthetic hormones are produced by altering the natural structure of the natural hormone in order to obtain a patent. This changes not only its structure but also its effect on the body. Many pharmaceutical hormones are derived from animal sources. Horses, pigs, and sheep are commonly used (the widely known drug Premarin gets its name from pregnant mare urine). In the human body, these hormones are foreign and do not have all the necessary co-factors for them to do their job properly. In some cases they do not respond to the enzymes that render them inactive after they complete their goal, and they continue to function even when unwanted. This can lead to more complicated problems related to estrogen dominance. In contrast, natural hormones are identical to those produced by the body. All the necessary enzymes and co-factors that are available in the human body make the natural hormones work safely and efficiently.

Contact:
Dr. I. Michael Borkin, NMD. has been in professional practice for 17 years. Dedicated full time to endocrine research, he is an independent medical/nutritional consultant and heads one of the most progressive research labs in the country. A pioneer in transdermal delivery, his ideas have given birth to some of the most innovative therapies in Naturopathic Medicine, including N.E.S.T. (Neuro Emotional Sensory Training) and Q2m (Quantum Magnetic Manipulation). He is a past president of the California State Naturopathic Medical Association. Tel: 805-496-5448.