HRT-MORE BAD NEWS

In the second part of our special report, we catalogue the little known side effects of a drug that is more likely to make you ill than add sparkle to your life.

Hormone replacement therapy has become so enshrouded in a myth of beneficence that it has been referred to more than once as “the most important preventive medicine of the century”.Indeed, John Studd of King’s College Hospital in London, who has probably done more to promote this drug than any other researcher, is so confident of its benefits that he dismisses the need for any tests, prior to or during its use.

“As all of the effects of long term HRT seem to be protective, with the questionable exception of breast cancer it is illogical to recommend that these women need any extra monitoring,” he announced (J Royal Soc of Medicine, July 1992).

In our opinion, however, future generations will look back upon HRT as the biggest medical bungle of the century. Ever since its launch, doctors have played statistical games with this drug, using loosely assembled observational studies to infer a host of future benefits, like protection from brittle bones or heart disease. This host of theoretical benefits, of course, are supposed to compensate for the well established risks. A drug that will increase your breast cancer risk by 60 per cent doesn’t look so bad when it promises to half your chances of getting heart disease.

Last month (WDDTY, vol 4 no 9), we exposed the shoddy science behind these claimed benefits. Without these, all HRT offers is a grocery list of potentially fatal side effects the subject of this second instalment of our special report.

No one really understands the best way to take this drug, and there is little control over the amount of estrogen which gets released into the blood stream. The most popular way to take HRT is by mouth. However, via this route, women experience a number of gastrointestinal symptoms nausea, vomiting, abdominal cramps, bloating and may even develop jaundice.

That may be one reason why medicine came up with the skin (transdermal) patch, which bypasses the liver, resulting in higher levels of estrogen. However, a fifth of patients experience blistering, hyperemia (increased blood flow in the area) and discoloration with this method.

Consequently, an increasing number of doctors now use estrogen implants, which require a small outpatient operation to insert the pellets under the skin.

Estrogen implants (and even patches) appear to create a “tolerance” for estrogen that some doctors warn is similar to addiction; the woman has higher than normal levels of estrogen in the blood, but nevertheless complains of the return of menopausal symptoms in increasingly frequent intervals. Although these implants are supposed to last for six months, many users complain of a return of symptoms three to nine weeks later.

This phenomenon called “tachyphylaxis,” (which means, literally, “too much prevention”) occurred in 3 per cent of a sampling of 1000 women in a study by the Dulwich Hospital Menopause Clinic in London (Br J Ob and Gynae, October 1990).

After examining a number of studies, Dr Thomas Bewley, former president of the Royal College of Psychiatrists, and Dr Susan Bewley, a gynaecologist at the University College Hospital, London, concluded that this dependence “occurs in 15 per cent of cases”. They wrote: “Estrogens are psychoactive. They lift mood, can be given by injection, and their use has powerful psychological effects (The Lancet, 1 February 1992).”

Doctors, however, have turned this potential for dependence on its head. In a wonderful example of blame the patient justification, John Studd, who helped conduct the study, concluded that women who become dependent have psychiatric problems, requiring larger than normal estrogen levels.

The Bewleys dispute this finding. “No convincing evidence has linked depression with the menopause per se,” they say. “However, estrogen treatment improves depression scores after surgical menopause and mood after the natural menopause, though there is a striking placebo response.”

It may simply be that the estrogen sensitive cells in the bodies of women continually blasted with high doses of the hormone have lost the ability to respond, according to endocrinologist Professor Howard Jacobs of Middlesex Hospital in London (BMJ, 5 December 1992).

Or, as Studd himself implies, early use of estrogens, whether in HRT to control PMT or the Pill, may set up an increased need for replacement therapy. Or it may be that HRT creates artificially high levels of estrogen in the body, triggering a hormone “crash” when these levels fall even slightly, exacerbating ordinary menopausal symptoms.

Ordinarily, the body’s pituitary glands and ovaries work in exquisite tandem, constantly adjusting estrogen levels to fit the body’s need of the moment, like a car set on automatic, says Dr Ellen Grant, author of Sexual Chemistry (Cedar, London 1994). HRT, which delivers a constant level of estrogen, she says, is like having a car stuck in a single gear.

Another problem with estrogen implants is that endometrial stimulation a potential cancer causing reaction can occur up to two years after stopping the drug. These days, it is acknowledged that using estrogen alone on a woman with a womb can increase her chances up to twenty fold of getting endometrial cancer after several years (see box, p 3). This is because estrogen causes rapid proliferation of endometrial cells (as it does in pregnancy).

To counteract this, most women are given the additional artificial hormone progestogen (progestin in the States) for 10-12 days per month, which imitates the second half of the menstrual cycle, producing withdrawal bleeding.

Researchers from the Menopause Clinic at King’s College School of Medicine and Dentistry found that endometrial stimulation in women given the implants occurred for an average of two years after the estrogen was finished (BMJ, 17 February 1990).

What this means is to lower your risk of getting endometrial cancer, you have to commit to taking oral progestogen for two years or more after the estrogen has been exhausted.

Most pro-HRT literature concentrates on the supposed euphoria experienced by women on the drug. What they don’t discuss is that many maybe even a majority experience a host of side effects with estrogen or progestogen.

Besides withdrawal bleeding, which many women find objectionable, progestogen causes a plethora of other side effects. These include PMT like symptoms breast tenderness, bloating, abdominal cramps, depression, anxiety and irritability (BMJ, 5 December 1992) in short many symptoms HRT was supposed to treat.

In an attempt to minimize these side effects, particularly withdrawal bleeding, some doctors give continuous progestogen. However, this commonly leads to breakthrough bleeding and nullifies the long term protective effects against endometrial cancer. In one study (Ob and Gyn, December 1991) of 41 patients who’d used the continuous combined estrogen and progestogen therapy for up to 10 years, six women had episodes of breakthrough bleeding, two of whom had benign endometrial tumours and two, endometrial cancer.

Far from being protective, the addition of protestogens in HRT can cause a slight increase in the risk of breast cancer (The Lancet 1991; 338: 274-7 and The New Eng J of Med, 15 April 1993).

Progestogens have also been shown to cancel out the supposed protective cardiovascular effects of estrogens (WDDTY vol 4 no 9); in one study it was postulated that the rate of mortality due to coronary artery disease may be higher among postmenopausal women receiving estrogen progestogen than among those receiving estrogen alone (Fertil Steril 1988; 49; Supple 2:9S-15S).

This may be because added progestogens reverse some of the favorable effects of estrogen on blood cholesterol levels, such as blunting the rise in high density lipoprotein cholesterol (Am J Med 1991; 90: 584-9), although one study showed the reverse (New Eng J Med, 15 April 1993).

“If the addition of progestin reverses even 5 to 10 per cent of the relative benefit of the estrogen replacement therapy with regard to ischemic heart disease,” write Drs Lee Goldman and Anna Tosteson at Brigham and Women’s Hospital in Boston, “its net effect as compared with unopposed estrogen therapy would probably be detrimental even if the entire increase in the risk of endometrial cancer is eliminated (New Eng J of Med, 12 September 1991).”

Although medicine maintains that the “natural” estrogens of HRT don’t have the same risk of thrombosis as the Pill, the continuous estrogen progestogen combination has demonstrated an ability to cause worrying changes in the blood. In a study of 60 women on the mixed treatment, changes were noted in blood coagulation and fibrinolysis (ability of the body to break up blood clots). Two women developed thrombosis.

“These changes could be an expression of hypercoagulability [increased tendency for blood to clot] and increased risk for thromboembolism,” the researchers concluded (Br J of Ob Gynae, October 1990).

Progestogens can also alter your glucose and insulin levels (Clinical Therapeutics, Sept-October 1990), cause higher than normal levels of calcium, hepatitis, liver cancer (including peliosis hepatis, a life threatening complication), jaundice, excess fluid, with or without heart failure and virilization such as increase in facial hair, and deepening of the voice, which can be irreversible.

HRT also appears to cause or increase the severity of migraines because it causes vascular overreaction (J of Neurology 240 (3): 195-6, 1993). Dr Ellen Grant, long time opponent of the Pill and HRT, published a study showing most patients had fewer headaches when they stopped smoking and taking hormones (The Lancet, 1979; i: 581-2).

Other studies show that HRT exacerbates endometriosis (Australian and NZ J of Ob & Gynae 32(4): 384-5, November 1992) and doubles your chances of contracting urinary tract infection (J of Amer Geriatrics Soc (40 (8): 817-20, August 1992).

This is in addition to all the other side effects of estrogen: a two to three fold increase in the risk of gallbladder disease, elevated blood pressure, enlarged and tender breasts, changes in the shape of the eyes and depression.

If you decide that all these risks aren’t worth taking just to rid yourself of hot flushes, there are many alternatives. Nutritional doctors like Dr Grant say that the kind of menopause you experience, like your degree of morning sickness or PMT, simply reflects your nutritional state. In her experience, if you sort out allergies, nutritional inadequacies (after undergoing appropriate tests measuring mineral levels) and any lingering genital infections, you should sail through this important transition virtually without symptoms (see WDDTY vol 1 no 9 for more suggestions).