The Pill Turns 50: Medicine That Makes You Sick

Recently three major health stories appeared in the Washington press in less than two weeks that were an occasion to pause and reflect.

First, the Potomac Conservancy made headlines about the contamination of rivers and drinking water in major metropolitan areas, including Washington DC. Contaminants include not only bacteria, industrial chemicals and agricultural pesticides but also potentially endocrine-active pharmaceuticals, such anti-depressants, contraceptive sex hormones, antibiotics and personal care products.

Next came the report of US Preventive Services Task Force, an independent body which studies mortality from common diseases, issuing new guidelines for mammographic screening for early detection of breast cancer. Breast Cancer remains the second highest cause of mortality of American women since it began to rise in the 1970s.

Finally, the Centers for Disease Control (CDC) reported the annual statistics for sexually transmitted diseases. In 2008 there was a record number of new cases of Chlamydia – a whopping 1.2 million new cases, a rise in the number of new cases of syphilis and an all-time record of 19 million total cases of all forms of STDs.

To connect the dots between these stories one has to ask: Could steroid-based sex hormone contraceptives be a common thread?

Hard to believe until you consider the evidence.

A pill is born

The first sex hormone-containing pill, a synthetic steroid called Norethindrone, was developed by organic chemist Carl Djerassi in Syntex Laboratories in Mexico City. Djerassi was developing a synthetic progestin for menstrual irregularities. His product turned out to be a powerful inhibitor of ovulation, but he had not anticipated that the estrogen-with-progestin combination oral birth control pill (COCP) would have other effects upon women. Only after many years was this combination suspected as the culprit in many unexpected side-effects, including blood clots, diabetes, depression or anxious emotional states experienced by women.

That some of these side-effects can be serious is confirmed by a new report in the January 2010 edition of Obstetrics and Gynecology of conclusive evidence for significant loss of bone mineral density when a woman uses Depo-Provera (a long acting injectable form of progestin-only contraceptive) for more than two years.

An evaluation by the International Agency for Research on Cancer ( IARC) released in 1999 classified oral contraceptives as a Group 1 carcinogen: "There is sufficient evidence in humans for the carcinogenicity of combined oral estrogen-progestogen contraceptives." The weight of evidence indicated an increased risk of breast cancer which was greater for women who were under age 35 at the time of diagnosis and who had begun using contraceptives before their 20th birthday. In a follow up 2005 report, IARC estimated that worldwide more than 100 million women were using some form of COCP. IARC re-iterated its classification of oral contraceptives as Group I carcinogens.

The Mayo Clinic Proceedings in 2006 published a meta-analysis of 23 studies done in several countries about breast cancer risk and usage of oral contraceptives. Dr Chris Kahlenborn, one of the principal authors, stated that "if a woman takes combined oral contraceptive pills before her first full term pregnancy, she risks a 44 percent increased chance of developing pre-menopause breast cancer when compared to women who have never taken an OCP". Kahlenborn also found that "if a woman takes OCPs for 4 years or more prior to her first full term pregnancy, she suffers a 52 percent increased risk".

Drinking water contamination

Yet, what was most surprising to Dr. Meg Meeker, pediatrician and adolescent medicine specialist, was her observation that many of her adolescent girl patients who had begun to engage in sexual encounters were showing signs of clinical depression.

The U.S. Geological Survey in 2002 found one or more pharmaceuticals in 80 percent of the streams it had tested. In 2006 the Los Angeles Times reported that sewage contains traces of medications like antibiotics, anti-depressants, birth-control hormones, Viagra, Valium and heart drugs.

Shane Snyder, lead toxicologist at the Southern Nevada Water Authority, said: "There is no place on Earth exempted from having pharmaceuticals and steroids in its wastewater. This is clearly an issue that is global, and we are going to see more and more of these chemicals in the environment, no doubt about it."

The Potomac Conservancy found similar water conditions in the Washington, D.C. area. Mirroring other regions of the country where biologists have found frogs contaminated with Prozac, insects on anti-seizure drugs and algae killed by antibiotics, the waterways draining the Shenandoah Mountains and tributaries flowing into the Potomac River have witnessed fish kills since 2002. The unexpected observation was that most of the dead male fish had inter-sex characteristics and that there was a disproportionate number of female fish. Further examination by the US Geological Survey of the Potomac tributaries revealed that 80 percent of the male fish had the inter-sex condition.

While the concentrations of some of the pharmaceuticals found in drinking water sources, including estrogens and fertility drugs, are in the parts per billion, comparable to putting a few drops in an Olympic-sized pool, the effects these may have on humans remains unknown. What is known is that on the level of endocrine systems, fish and humans function in very similar ways. What happens to fish may be signaling future disorders for humans.

This was highlighted in the Proceedings of the National Academies of Science (2008) in a report of an experiment demonstrating that young male trout develop abnormal numbers of chromosomes in sperm when the young fish were exposed over 50 days to concentrations of the contraceptive estrogen ethinyl estradiol (EE2), comparable to concerntrations of EE2 discovered in waterways in various regions of the U.S. Exposure to this very low concentration of EE2 resulted in a 25 times greater number of abnormal sperm. When the sperm from exposed male trout fertilizes the eggs of female trout not similarly exposed to EE2, the fish embryos that develop demonstrated a 58% increase in the number of abnormal embryos, some with too many chromosomes, some with too few.

What this means for humans is unknown. What is known is the observation that human embryos, when analyzed after miscarriage, frequently demonstrate similar abnormal number of chromosomes.

Contraceptives: a form of endocrine-disrupting chemicals

In 2009 the professional association for endocrinologists, the Endocrine Society, issued a strong statement on endocrine-disrupting chemicals. The evidence suggests that exposure to multiple endocrine disrupting chemicals at developmental stages has the potential to affect any hormone-sensitive body system, including the breast and the hypothalamic-pituitary-ovarian system in women, and the testes and prostate gland in men.

The Endocrine Society appealed to the precautionary principle, stating: "This principle is key to enhancing endocrine and reproductive health, and should be consulted to inform decisions about exposure to and risk from any potential endocrine disruptor."

And: "The public may be placed at risk because critical information about potential health effects of endocrine disrupting chemicals to which Americans are exposed is being overlooked in the development of federal guidelines and regulations."

The pill's link to STDs

Yet, what was most surprising to Dr. Meg Meeker, pediatrician and adolescent medicine specialist, was her observation that many of her adolescent girl patients who had begun to engage in sexual encounters were showing signs of clinical depression.

Are there any strong associations between use of steroid-based OCPs and sexually transmitted diseases? The CDC's answer is yes.

A review of 83 studies published in the Journal Contraception in 2006 found that combined oral contraceptives and Depo-Provera use generally had a positive association with cervical chlamydial infection. Chlamydia infection and other inflammatory STDs such as Syphilis or genital Herpes are reported by the CDC to increase the risk of transmission of Human Immunodeficiency Virus infection. Chlamydia is well known as the leading preventable infection that can cause a severe condition called Pelvic Inflammatory Disease, which, if not treated, can result in female infertility.

The recent STD report for 2008 from the CDC states that adolescent girls between the ages of 15-19 account for 27 per cent of the total new cases of chlamydia and gonorrhea. While acknowledging that adolescent boys have a similar prevalence of STDs, the CDC insisted that because of "biological differences" young women have a greater potential to suffer consequences to their health than young males.

Depressing sex

Yet, what was most surprising to Dr. Meg Meeker, pediatrician and adolescent medicine specialist, was her observation that many of her adolescent girl patients who had begun to engage in sexual encounters were showing signs of clinical depression.

In her book, Strong Fathers, Strong Daughters (2007), she says: "Kids get depressed when they experience a loss for which they cannot express a healthy emotion. This is very common with sexual activity. When a girl has sex, she loses her virginity and very often loses her self-respect with it".

That clinical observation of one pediatrician is supported by findings of researchers interested in any association between teenage sexual experimentation, drug use and depression. Denise Hallfors et al write in the American Journal of Preventive Medicine (October 2005) that for girls even a modest involvement in sexual experimentation or substance use elevated depression risk. In contrast, boys exhibited little added risk of depression with sexual experimental behavior, although binge drinking and frequent use of marijuana contribute substantial risk.

Thanatos syndrome revisited

In Walker Percy's 1987 novel, The Thanatos Syndrome, Dr. Tom More returns to his home town and family to restart what remains of his practice of psychiatry after serving a felony conviction for selling prescriptions for narcotics. After a few weeks of re-establishing contact with some of his former patients, he notices a profound change in his patients, with unusual mood changes, increased ability to recall the location of obscure names of places and the ability to make complex numeric calculations. In addition his patients all seem to have become hyper-eroticized, exhibiting outlandish sexual advances that persons with intact higher-order self-control would recognize as outside the range of socially acceptable behavior.

The contraceptive pill was sold as the scientific panacea for ultimate sexual liberation. Its real-time effect has been a form of "lobotomy" of reason and good judgement, both of users and prescribers.

He postulates something has changed his patients. With the help of an epidemiologist, More learns that toxic, radioactive sodium has been released from a nearby nuclear power plant and that the water with the heavy sodium is being deliberately channeled through an unauthorized and hidden pipe into the drinking water supply. Behind this scheme are some of More's medical colleagues, who discovered, that dosing the water supply with low concentrations of heavy sodium had the effect of suppressing the cognitive functioning of antisocial types like alcoholics, drug addicts, prostitutes or those confined to the local jail. The docs feel justified in what they are doing. They want Dr. Tom to join them when they discover he knows what they are up to. Dr. Tom knows better.

It appears that for the last 50 years, something similar has been happening to America. The contraceptive pill was sold as the scientific panacea for ultimate sexual liberation. Its real-time effect has been a form of "lobotomy" of reason and good judgement, both of users and prescribers. It is time the medical establishment recognized its complicity and returned to that simple principle for which it gained the enviable respect and autonomy of action it merited as the premier profession that advocated for the unprotected and unknowing: "Above all, do no harm."