Getting hooked on HRT

Hailed as an elixir for menopausal women, oestrogen replacement can have side effects and leaves some women begging for more, says Annabel Ferriman

Barbara Bye thinks that oestrogen is the best thing since sliced bread. She was briefly deprived of it at the age of 35, after a hysterectomy for heavy periods, during which time she lost not only her womb but also her ovaries (which produce the hormone), so she should know.

"I was not given anything for two or three months and started going through an early menopause, which was horrible," she recalls. But I was then given an oestrogen implant (a pellet of slow-release oestrogen, inserted under the skin) and felt marvellous. A new one was inserted every five months for five years and I really felt good."

Her sexual energy, she says, was at an all-time high. "In fact, my libido was so strong that my partner was glad when I was getting to the end of the five months and the implant was running out, because he could get a bit of rest."

But then things started going wrong. Mrs Bye, who lives in Addlestone, Surrey, developed bladder problems and felt as if she needed to pass water all the time. "It got so bad that I stopped going out."

When she was investigated, it was discovered that the level of oestradiol - one of the oestrogen hormones, in her blood - was abnormally high: 1,700 (picomoles per litre) instead of the usual 500-700. Doctors said she had overdosed and refused to give her any oestrogen for a year, until the levels had fallen to normal.

Mrs Bye, who is now 42 and works as a sales administrator, went through a type of cold turkey, suffering withdrawal symptoms. "Coming off the implants has been awful," she says. "For the first six months I was all right, because the effects were still there. But for the next six months, as the levels in my body fell, I was murder to live with, snapping at everyone."

High levels of oestrogen had also protected Mrs Bye from the worst symptoms of menopause, which now hit her with a vengeance. "I now get tired, have hot flushes, don't sleep well and lack confidence. My bladder has improved, but that is the only thing that has got better.'

Can a woman become addicted to oestrogen? Several gynaecologists say that some of their female patients taking hormone replacement therapy (HRT) in the form of implants to reduce their menopausal symptoms are becoming so dependent that they demand more oestrogen long before a new implant is due, complaining that the current dose no longer works and that their symptoms are returning.Self-medication with oestrogen patches and creams, and over-medication, with women turning to more than one doctor for treatment, can exacerbate dependency on the hormone.

"I recently saw a patient who, as well as using both oestrogen tablets and patches, had rubbed in half a tube of oestrogen cream and had oestradiol levels of 19,900," says Mr John Studd, a consultant obstetrician and gynaecologist at the Chelsea and Westminster Hospital, London.

High levels of oestrogen in the blood may make a woman feel energetic and sexy but, as in Mrs Bye's case, they can result in problems. In addition, the fillip a high dose of oestrogen gives can backfire: in some women who have had implants for many years, levels of the hormone become so high that the body's oestrogen receptors, which transmit messages to the brain, are turned off. The result is that women feel as if they are not getting enough oestrogen - even though their bodies are actually awash with it.This condition, known as tachyphylaxis, seems to be confined mainly to women who take oestrogen implants, which appear to have a less even effect than patches and creams. If a woman has tachyphylaxis, she has to be taken off HRT to bring down oestrogen levels, which is where "withdrawal" problems can begin.

"I have had considerable difficulty in weaning women off their implants," says Mr Kevin Gangar, a consultant obstetrician and gynaecologist at Ashford Hospital, who has written widely about tachyphylaxis. "The women need a great deal of emotional and psychological support. They seem to go through a kind of cold turkey. It can take a very long time, sometimes several years, for their blood levels to return to normal."

At least 1.5 million women in their forties, fifties and sixties are taking HRT to prevent or lessen menopausal symptoms. This may be in the form of oestrogen alone for those who had the womb removed, or oestrogen combined with progestogen to protect against cancer of the womb lining. Five per cent, or 75,000, take it by means of an implant. It is estimated that tachyphylaxis affects at least 5 per cent of them, or 4,000 women a year. Mr Gangar believes that oestrogen implants are an effective way of delivering HRT but that they have to be properly monitored.

"Some doctors believe that when menopausal symptoms recur, whether it is after four months or five months, you can just routinely insert another implant, without carrying out a blood test to check on oestrogen levels, which may still be relatively high.

"I believe in monitoring oestrogen levels, by carrying out blood tests routinely. I would not usually put in another implant if the level of oestradiol is above 500, and absolutely not if it is above 1,000." Oestrogen implants should, he says, merely replace the levels found pre-menopause: for someone in her mid-twenties, the average monthly level is 500.

Doctors are worried not only about the possibility of oestrogen dependence but also about possible long-term effects of abnormally high levels in the blood.

"Common sense would suggest that if you take a natural substance like oestrogen and give it to women at supraphysiological levels [above those that normally occur in nature], it is undesirable," says Mr Gangar.

"It might have adverse side-effects, similar to those we have seen associated with the birth-control pill, such as an increase in blood clotting. There is also some epidemiological data to suggest that breast cancer might be connected, in a dose-related manner, to the amount of oestrogen in the body.

Women do not need oestrogen at such high levels to gain the protective effects that the hormone confers against cardiovascular disease and osteoporosis, or thinning of the bones, he adds.

His views are confirmed by other specialists. Mr Anthony Parsons, consultant obstetrician and gynaecologist at Hospital of St Cross, Rugby Warwickshire, says: "We come across tachyphylaxis relatively often. It can be avoided by giving a blood test to anyone whose implant does not seem to be lasting. We do not know whether high levels of oestradiols in the blood are dangerous, but if they were high for long, one would wonder if they could lead to an increase in blood clots."

Some specialists, however, feel tachyphylaxis has been overestimated and that the problem lies not with HRT implants but with overprescribing. John Studd says the condition only occurs where "the wrong dose is prescribed too often. Some doctors are prescribing 100mg every three months and getting very high levels."

Mr Studd also dismisses anxiety about women becoming addicted to oestrogen. Women are only dependent on oestrogen in the same way that all of us are dependent on things that make us feel good and improve our lives: it is like someone being dependent on spectacles."

Dr Tim Garnett, medical director of Organon, the company that makes the implants, says most doctors are more careful about dosages than they were five years ago. The sales of the lower doses, 25mg and 50mg implants, have increased dramatically, while those of 100mg have fallen.

He points out the problem is not confined to women on implants. "When I was in practice, I remember seeing a woman in my consulting room who was wearing 14 patches. During the consultation she said that she did not feel well and stuck on an another.

"Women who take HRT often have unrealistic expectations. They sometimes think of it as the elixir of life, whereas it cannot solve problems of unemployment, children leaving home, boredom with one's husband. When it does not solve all their problems, they want to increase their dose."

THE DIFFERENT FORMS OF HRT

Oestrogens are taken alone if a woman has had a hysterectomy, or with a progestogen if she still has her womb. The progestogen counters the effect of the oestrogen which, if taken alone, can stimulate the womb lining and cause cancer.

Tablets are taken several days a month. The woman must take them on the right days and a higher dose is needed to compensate for the loss that occurs as the drug passes through the digestive tract.

Patches are plasters applied to the skin, usually twice a week. The hormones pass directly into the blood, avoiding the digestive system and having less effect on the liver, but they can irritate the skin.

Implants usually contain a six-month supply of hormones. They are inserted as small pellets in the buttocks, abdomen or thighs, under local anaesthetic. This means the dose is fixed and cannot be altered unless the implant is removed. Implants can result in higher oestrogen levels than tablets or patches. Implants come in doses of 25mg, 50mg and 100 mg.

Cream is put into the vagina with an applicator. It is absorbed into the bloodstream, as well as having a local effect on the vaginal lining.