Life Extension Magazine April 2006
By Dr. Sergey Dzugan and Armond Scipione
Two recent studies of progesterone supplementation validate what the Life Extension Foundation has contended for the past 12 years: restoring the body’s supply of natural progesterone confers multiple health benefits, including balancing blood sugar levels, promoting normal sleep, reducing anxiety, and stimulating new bone growth.1,2
Controlled studies and most observational studies published in the last five years suggest that the addition of progestins (synthetic progesterone) to hormone replacement therapy, particularly in a continuous combined regimen, increases the risk of breast cancer compared to estrogen alone.1 While the results of clinical trials may accurately assess the risks associated with synthetic progestin compounds and estrogen/ progestin combinations, the data do not reflect what might have been the result had natural progesterone been used instead of synthetic progesterone.2
Recent studies suggest that the addition of natural progesterone in a cyclic manner does not increase breast cancer risk. These findings are consistent with in-vivo data suggesting that progesterone does not have a detrimental effect on breast tissue.1
Nature has given progesterone to men and women alike to balance and offset the powerful effects of estrogen. Some of the most common concerns of aging women are weight gain, insomnia, anxiety, depression, and migraine. For other women, even more debilitating conditions such as cancer, uterine fibroids, ovarian cysts, and osteoporosis now play a predominant role in their lives. As men age, complaints of weight gain, loss of libido, and prostate enlargement top their list of health concerns. Many physicians and scientists are becoming more aware of a common link between these symptoms and conditions. That common link is often an imbalance between two sex hormones, progesterone and estrogen.
In menstruating women, progesterone is one of two primary sex hormones (the other being estrogen) produced each month by the ovaries. During the first 14 days of the menstrual cycle, the ovaries secrete increasing amounts of estrogens. This two-week period is named the follicular phase. Halfway through a woman’s cycle, around day 14, one of her two ovaries will ovulate and release an egg. After ovulation, the ruptured follicle from which the egg has been released is transformed into the corpus luteum and begins producing progesterone. The portion of the menstrual cycle that follows ovulation, called the luteal phase, is orchestrated by progesterone. As its name implies, progesterone prepares (promotes) the womb for pregnancy (gestation). If the egg fails to be fertilized and no pregnancy occurs, the production of both progesterone and estrogen will rapidly decline, resulting in a period (menses).
If pregnancy does occur, the placenta begins to secrete progesterone (the corpus luteum continues to produce progesterone as well). In fact, by the fifth month of pregnancy, the placenta itself secretes sufficient progesterone such that the corpus luteum is no longer essential to maintain pregnancy. These high levels of progesterone act as natural birth control agents, shutting down ovulation for the duration of the pregnancy.
Plasma concentrations of progesterone in women vary throughout the menstrual cycle. During the follicular phase, plasma concentrations of progesterone are generally below 2 nanograms per milliliter (ng/mL). Throughout the luteal phase, which prepares the body for pregnancy, progesterone levels can rise to 28 ng/mL. Dramatic increases in progesterone occur throughout pregnancy: plasma levels may reach 40 ng/mL in the first trimester, and climb to 100-200 ng/mL near the delivery date.3
Progesterone is a key precursor to other steroid hormones, including cortisol, testosterone, and the estrogens (estriol, estradiol, and estrone). When progesterone circulates in the blood, 90% is bound to a protein or albumin fraction. Only a small percentage (3%) circulates unbound.4
While a woman’s estrogen may eventually drop 40-60% below her baseline level by menopause, her progesterone level can drop even more dramatically. Although the adrenal glands still produce some progesterone, the decline in progesterone upsets the body’s natural hormone balance. Following menopause, a woman’s progesterone level drops to nearly zero.
Actions of Progesterone
Progesterone plays a key role in the tasks necessary for reproduction. Beyond preparation for pregnancy, progesterone has a multitude of effects throughout the body, many of which may be attributable to its ability to oppose the action of estrogen. Multiple physical and psychological problems at midlife are often caused by an imbalance between progesterone and estrogen. The term “estrogen dominance” describes the condition of lacking sufficient progesterone to counteract the effects of estrogen. A common misconception is that estrogen dominance results only from extremely high levels of estrogen. To the contrary, this condition also may be caused by normal levels of estrogen and relatively low levels of progesterone, or by low levels of estrogen and extremely low levels of progesterone.
Estrogen levels may be elevated by a number of external influences. Xenoestrogens (foreign estrogens) are among a group of chemicals known to alter hormone levels. Environmental pesticides, including those found on commercially grown fruits and vegetables, are perhaps the primary source of xenoestrogens. Cosmetics, shampoo, and plastics also may contribute to the accumulation of these foreign estrogens.
Progesterone’s many functions in the body include:
Natural vs. Synthetic Progesterone
When discussing progesterone, it is important to understand the difference between natural progesterone and the synthetic progesterone analogs called progestins. Progestogens is an umbrella term for both natural progesterone and the synthetic progestins, because they all have progestational effects in the uterus.
Natural progesterone is synthesized 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. Natural progesterone refers to bioidentical hormone products that have a molecular structure identical to the hormones our bodies manufacture naturally. The most effective form of bioidentical progesterone is called micronized progesterone USP. The process of micronization allows for steady and even absorption of the medication. Micronized progesterone is available only through a doctor’s prescription. An alternative is natural progesterone creams sold over the counter worldwide. Both the micronized progesterone and commercially available progesterone creams contain bioidentical progesterone.
Unlike progesterone, 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 profitable birth control products.
One of the most common progestins, medroxyprogesterone acetate (Provera®), has been linked to blood clots, fluid retention, acne, rashes, weight gain, and depression. Progestins are also able to bind to glucocorticoid, androgen, and mineralocorticoid receptors, which explains the wide range of side effects many women experience while taking progestins.17,18 The vast majority of research studies have been conducted using progestins rather than natural progesterone, which explains the disparity and negativity of the results.
The FDA has also approved a drug called Prometrium®, an oral pill containing 200 mg of natural progesterone taken daily. Because orally administered progesterone is metabolized by the liver, it may be contraindicated in patients with certain liver conditions.
Natural progesterone cream may be more efficiently used, since its highly lipophilic (fat-soluble) molecules of low molecular weight allow it be well absorbed through the skin. Another advantage of topical natural progesterone cream is that individualized dosing can be easily facilitated by varying the amount of cream applied.