The television game show To Tell the Truth has appeared in various editions over the past forty years. The one I remember, from the fifties and sixties, featured Bud Colyer as the host and a celebrity panel made up of Tom Poston, Peggy Cass, Orson Bean, and Kitty Carlisle.

The game would begin with three consecutive individuals introducing themselves using the same name. “Hello,” contestant number one would say, “My name is Bob Brown.”

Contestant number two would then step forward and announce, “Hello. My name is Bob Brown.” Contestant number three would make the same declaration.

The celebrity panel would take turns asking questions as they attempted to correctly identify the real Bob Brown and expose the imposters. After the questioning was completed and the panel had cast their votes, Bud Colyer would turn to the contestants and utter the now famous words, “Will the real Bob Brown please stand up!”

After some shuffling of chairs and two or three fake attempts by the imposters, the real Bob Brown would rise while the pretenders remained seated. He would say a few words about himself, then he and the other contestants would depart and, following a commercial break, a new game would begin.

Judging by the number of women who consult me with concerns about the dangers of progesterone it appears that many physicians and journalists are playing a game of To Tell the Truth with progesterone. Take, for example, the Internet site Answers.com, which gives two definitions of progesterone:

1. A steroid hormone, C₂₁H₃₀O₂, secreted by the corpus luteum of the ovary and by the placenta.
2. A drug prepared from natural or synthetic progesterone, used in the prevention of miscarriage, in the treatment of menstrual disorders, and as a constituent of some oral contraceptives.

The website does mention at one point in the body of the article that progesterone should not be confused with other compounds that have similar effects, but the author then goes on to warn of the dangers of progesterone when citing the results of a study involving a chemical called medroxyprogesterone acetate.

A distinction between the progesterone molecule and progesterone-like drugs is almost never made by physicians. When I attend medical meetings I find that speakers commonly use the term progesterone when referring to a progesterone-like substance such as medroxyprogesterone acetate or norethindrone acetate. It is therefore not surprising that the results of studies using progesterone-like substances are commonly applied to progesterone as well. The practice of allowing drugs such as Provera (medroxyprogesterone acetate) and Aygestin (norethindrone acetate) to introduce themselves as progesterone has created a great deal of confusion about the use of progesterone supplementation. It is time to tell the truth.

Progesterone is a naturally occurring hormone that is produced not only by the ovaries in women, but in the testes in men and the adrenal glands and the brain in both sexes. During pregnancy it is also manufactured by the placenta.

Progesterone has many functions. It is best known for its effects on a woman’s reproductive cycle and pregnancy. As a woman’s monthly menstrual cycle begins estrogen is released to stimulate growth of the uterine lining. Progesterone production rises at mid-cycle to cause the lining to mature and ready itself to accept a pregnancy. If a pregnancy is not present at the end of the monthly cycle, progesterone levels fall sharply. This triggers a release of the uterine lining as a menstrual period. If a pregnancy is present, progesterone levels remain high. Failure of the ovary to maintain high progesterone levels or failure of the placenta to take over progesterone production is believed to trigger a miscarriage.

Progesterone blocks the production of breast milk and inhibits contraction of uterine muscle. It is believed that a drop in progesterone is one of the factors that trigger labor and subsequent milk production. In the adrenal glands progesterone is used to manufacture other hormones including aldosterone, which regulates fluid balance, cortisol, which helps the body adapt to stress, and androstenedione, which is converted to estrogen and testosterone.

Progesterone is found in high concentrations in the brain where it protects and nourishes nerve cells. It is an effective mood stabilizer, acting through the same mechanism as lithium and valproic acid, drugs that are commonly used to treat bipolar disorder. Progesterone also supports memory and other mental functions. Because it protects the myelin sheath surrounding nerve fibers it is being examined as a support for multiple sclerosis patients. Multiple sclerosis is characterized by a loss of myelin sheaths and it has been observed that the progression of the disease often halts during pregnancy when progesterone levels are high.

Progesterone is a key player in the body’s temperature regulation system. It causes smooth muscle to relax, which opens bronchial tubes in the airways and prevents intestinal cramping. The hormone supports thyroid function and works to normalize blood clotting mechanisms.

Progesterone improves cellular oxygen uptake and encourages the body to burn stored fat to create energy. Because it stimulates the activity of osteoblasts, cells that are responsible for building new bone, progesterone is critical to maintaining and improving bone strength.

Progesterone supplementation is most effective when given as a lozenge that is absorbed through the lining of the mouth or as a cream that is absorbed through the skin. The reason for this is that substances that are ingested pass through the liver before being delivered to the heart and circulated throughout the body. This is a benefit in that it gives the liver an opportunity to break down toxic substances before they can reach the body as a whole, but it is a distinct disadvantage when the desire is to deliver an intact hormone to the sites where it is needed. Using the oral mucosa or the skin as a point of entry bypasses the liver and allows the intact progesterone to reach the locations where it is needed.

Progesterone supplementation is beneficial in a number of conditions. It is quite effective in restoring menstrual irregularity when the normal cycle has been disrupted. It can control heavy, prolonged, or irregular menstrual bleeding in most instances. It can effectively prevent the symptoms associated with premenstrual syndrome such as mood swings and fluid retention. Because it counterbalances the effects of estrogen, progesterone supplementation can prevent or reverse estrogen induced conditions such as fibrocystic breast disease and uterine fibroids. It also appears to dramatically reduce the risk of developing uterine or breast cancer.

Progesterone supplementation is of utmost importance during the postmenopausal phase of a woman’s life. Restoring levels in the brain can stop mood swings, enhance memory, and improve sleep quality. As it supports thyroid function and stimulates the burning of fat weight gain can be slowed or reversed. It can also prevent or even reverse postmenopausal bone loss. It is therefore unfortunate that most physicians are reluctant to prescribe progesterone supplementation and many women are afraid to use it based upon a case of mistaken identity.

Much of today’s confusion about the nature of progesterone can be traced back to a study of a drug called PremPro. The study was abruptly terminated in July, 2002 when intermediate results demonstrated a 24 % increase in breast cancer, a 29 % increase in heart attack, and a 41 % increase in the incidence of stroke in women on the drug.

News stories at the time reported that the combined use of estrogen and progesterone had been shown to involve serious risks. The fact that the women in the study were not receiving progesterone, but the imposter, medroxyprogesterone acetate, was rarely, if ever, mentioned. Some news sources subsequently admitted that they had confused progesterone with an altered form of the hormone, but the damage had been done. Reports of the dangers of progesterone supplementation continue to be widely circulated.

Medroxyprogesterone acetate (MPA) is quite effective in imitating the effects of progesterone upon the uterine lining. The similarities stop there, however. The two substances behave much differently elsewhere in the body.

MPA tends to cause weight gain; progesterone stimulates fat burning and weight loss. MPA is associated with depression and sleep disturbances; progesterone eases depression and improves sleep quality. MPA increases the risk of abnormal blood clots, no such risk has been found with progesterone. MPA increases the frequency of headaches, particularly migraine headaches; progesterone decreases the frequency of migraine. MPA can trigger release of breast milk; progesterone blocks the production of breast milk. MPA can cause fatigue and sleepiness; progesterone tends to improve energy levels.

It is therefore not surprising that while MPA has been shown to increase the risk of breast cancer studies, such as that of Dr. Gino Tutera that followed 976 women supplementing progesterone over a ten year period, have shown no such effect. To the contrary, evidence is accumulating that suggests progesterone has a protective effect and actually reduces the risk of breast cancer over time.

The differences between progesterone and its imitators are being recognized by an increasing number of consumers. This is evident in the actions of the pharmaceutical giant, Wyeth. In October, 2005 Wyeth filed a petition with the FDA to restrict the availability of progesterone supplements. Citing safety concerns, Wyeth also called on the FDA to regulate compounding pharmacists, a role that has specifically been reserved for the individual states.

While Wyeth insists that their petition was presented due to concerns about patient health and consumer safety, the move was almost certainly a desperate attempt to protect the remaining market share of PremPro, the product shown to significantly increase the risk of breast cancer, heart attack, and stroke in those taking it. Sales of Wyeth’s Premarin family of drugs, including PremPro fell 68% between 2002 and 2004 (from $2,072,000,000 in 2002 to $1,275,000,000 in 2003 and $800,000,000 in 2004). Over that same period Wyeth’s profits declined by over 3 billion dollars.

The FDA initially set an April deadline for comments about the petition, but extended the deadline to May 4^th due to the outcry it received from physicians experienced in the use of true progesterone supplementation, compounding pharmacists who commonly prepare progesterone creams and lozenges, and women who had found true progesterone to be helpful in restoring their health. Nearly 30,000 responses were received, an unprecedented number, making it unlikely that the FDA will find in Wyeth’s favor, although the outcome remains in doubt.

It is time to end the current episode of To Tell the Truth. It is time for the real progesterone to stand up and proudly tell its story. It is also time for the impostors, including PremPro, to sit down and end the charade.