“Unwarranted fears should not be an obstacle to treatment”

Hormones were previously used extensively to treat symptoms of menopause, but since the early 2000s, their use has decreased drastically. According to Angelica Lindén Hirschberg, the low levels seen today indicate an unnecessary under-treatment.

In the mid-90s, approximately one in four women in Sweden received hormone treatment for symptoms of menopause. These symptoms include uncomfortable hot flashes and profuse sweating, which in turn lead to interrupted sleep. The treatment normally consists of the female sex hormone oestrogen along with progesterone. Today, only five per cent of women receive treatment, based on the amount of drugs being prescribed.

“Around one third of all women will experience severe menopausal symptoms, so there is a large degree of under-treatment. A few generations have suffered needlessly,” says Angelica Lindén Hirschberg, Professor of Obstetrics and Gynaecology at Karolinska Institutet.

This change began in 2002 with the results of a major American study, known as the Women’s Health Initiative (WHI). In it, 16,000 women between the ages of 50 and 79 were treated with hormones for five to seven years.

“The news for the gynaecology community was the observance of a somewhat increased risk of cardiovascular disease.  However, that risk turned out to primarily affect older women, who are not part of the main group needing hormonal drugs to treat menopausal symptoms. However, the media instead reported on an increased risk of breast cancer,” she says.

In the study, the treatment led to eight additional cases of breast cancer per 10,000 women and year, a risk increase of 30 per cent.

“This is considered to be a relatively small increase in risk. Compare this with obesity, i.e. a BMI of more than 30, which doubles the relative risk of breast cancer in postmenopausal women,” she says.

The study also included women without a uterus, who were therefore only given oestrogen (see fact box).

“Their risk of breast cancer decreased or remained neutral. In other words, oestrogen alone does not increase the risk, but the small increase is instead caused by the combination of progestin or progesterone and oestrogen,” she says.

Many were deterred from hormone treatment

The fact that many were deterred from hormone treatment was unfortunate, suggests Angelica Lindén Hirschberg. Not least for the women who enter early menopause. It can happen as early as in one’s 30s, but more often around 40 years of age, which is ten years earlier than normal. This affects one in a hundred women.

“These women need to receive hormone treatment. They are otherwise at increased risk of cardiovascular disease, osteoporosis, and in the long run deteriorated cognitive abilities, as in dementia,” she says.

The women need to receive hormone replacement therapy at least up until the age of normal menopause, around the age of 50.

“This is a message that I would like to communicate to the treating physicians. I have had patients whose GP has advised against continued treatment after five years. Another patient came to a mammography where the nurse told her ‘oh, you’re taking hormones – but they’re so dangerous’.  Guess whether she stopped taking them,” says Angelica Lindén Hirschberg.

The prescribing of hormonal drugs has thus decreased sharply, but something that is increasing on the other hand, according to Angelica Lindén Hirschberg, is that women want to be their own doctors.

“My colleagues and I see an increasing tendency for patients making their own cocktail of hormones bought online, often inspired by bloggers or some social media celebrity. This is something I would definitely not recommend. Hormones are potent substances, and it can turn into a whole mess of issues,” she says.

One reason is that hormones come in a number of different strengths and preparations, which all work differently. In addition, the complex interaction of different hormones is crucial to the effectiveness of the treatment.

“This means that even if the patient starts feeling better temporarily, incorrect use can lead to problems in the longer term, in the worst case to illness and cancer,” she says.

Study about synthetic or bioidentical hormones

Angelica Lindén Hirschberg has spent a long time researching sex hormones, both female and male. Next up is a study to compare synthetic hormones with bioidentical ones. Bioidentical hormones are chemically manufactured but have the same make-up as the body’s own, while synthetic hormones differ slightly from body identical hormones. In Sweden, synthetic progesterone, known as progestin, is traditionally used, whereas Germany and France among others primarily opt for bioidentical progesterone. There is now an increasing demand for these among Swedish women, which can be seen in the increased level of license prescriptions. One reason is that progestin can cause mood effects similar to those of PMS. Another reason may be that bioidentical progesterone taken at night can improve sleep, as it has a sedative effect.

“According to the few observational studies that have been conducted, bioidentical progesterone has a slightly lower risk of breast cancer than progestin, but on the other hand, it increases the risk of uterine cancer. In our randomised study, we want to examine whether there is any actual difference,” says Angelica Lindén Hirschberg.

The study will include 330 women with menopausal symptoms being treated with an oestrogen spray. Half of them will be randomly selected to also receive progestin, while the other half will be on bioidentical progesterone.  Neither participants nor researchers will know who is taking what, and the treatment will last for one year. This is not enough time to see any differences in the risk of cancer, which is a problem that the researchers will solve by measuring surrogate markers.

“We will be measuring so-called mammographic density before and after treatment. This means measuring the density of the breasts, i.e. the white parts in the image, which give an indication of increased risk of breast cancer. We will also be taking tissue samples from the endometrium,” she says.

If everything works out with funding and approvals, the study will start in the autumn.

“It will be interesting to see if there are any differences between the different variants. The study also gives Swedish gynaecologists an opportunity to gain experience of bioidentical hormones under controlled circumstances.”

Finally, what is the most common misconception about hormone treatment?

“That oestrogen causes breast cancer; there is no proof of this.  The more likely culprit is the progestin. We are not returning to the 1990s when women were treated with hormones to feel better in general, but unwarranted fears should not keep women from effective treatment if they are experiencing severe menopausal symptoms,” says Angelica Lindén Hirschberg.

Text: Lotta Fredholm, first published in Swedish in Medicinsk Vetenskap no 2 2019

Facts: How menopausal symptoms are treated

  • Symptoms such as sweating, hot flashes and interrupted sleep are systemically treated with oestrogen tablets, patches, spray or gel. Fragile and dry mucous membranes can be treated locally with an oestrogen cream.
  • Women without a uterus only receive oestrogen.
  • Women with a uterus receive supplementary progesterone to prevent the endometrium from building up, which can lead to cancer in the long term.