New study again links HRT and depression

Doctors are being urged to remain cautious when administering hormone replacement therapies (HRT) to women, after a new Danish study again linked HRT to depression.

The report released this week suggests that hormonal therapy administered “systemically” is associated with higher risk of depression, especially in the years immediately after initiation.

It also found that “locally” administered HRT, is actually associated with lower risk of depression for women 54 years or older.

Women’s health expert Professor Alex Polyakov from the University of Melbourne says the study wont surprise GPs.

“Depression is one of the side effects, but for some women it’s a risk worth taking because they are significant symptoms which can affect their quality of life for a long time, maybe even years,” Polyakov says.

He agrees with the report’s finding which says: “Women undergoing menopause who initiate systemically administered [HRT] should be aware of depression as a potential adverse effect, and locally administered [HRT] should be recommended when needed.”

During menopause, the levels of estrogen and progesterone decrease and 60% to 70% of women experience menopausal symptoms, including mood and cognitive disturbances. The latter might be prevented by hormone therapy.

The therapy can be administered “systemically” through tablets and patches. This puts the hormones into the bloodstream and they are distributed throughout the body.

Polyakov says ‘locally administered’ hormone therapies are administered via vaginal pessaries and therefore only small amounts are absorbed into the bloodstream.

To examine whether use of HRT during menopause was associated with a subsequent diagnosis of depression, the Danish team examined a nationwide register of more than 800,000 women aged 45 years between January 1, 1995, through December 31, 2017.

Follow-up was completed on December 31, 2018.

It found systemically administered HRT was mainly initiated before 50 years of age and was associated with a higher risk of a subsequent depression diagnosis. The risk was especially elevated the year after initiation of both treatment with estrogen alone and estrogen combined with progestin.

Locally administered HRT was initiated across all ages and was not associated with depression risk. It was, however, associated with a lower risk of depression when initiated after 54 years of age.

Read more from Cosmos: HRT and depression

Depression is one of the leading causes of disability worldwide. The report says: “Women are twice as likely as men to experience depression, suggesting that cyclic fluctuations in gonadal hormones—estrogen and progesterone—may contribute to this problem.”

The study included many women who were 45 in 1995, and Polyakov points out: “At that time HRT was widely prescribed for non-symptomatic causes.”

“It is a significant finding, but this study doesn’t demonstrate causation. It’s worth making women aware of these side effects though.

“The advice now is to give women the lowest dose for the shortest possible time to relieve symptoms. There is no question that GPs are well aware of the risks associated with HRT. The prescribing patterns have changed over the last 15 years.”

Depression is well known risk factor for hormone therapy of all kinds but the therapy isn’t always responsible. One gynaecologist pointed out other factors than menopause can lead to depression.

HRT is prescribed when many women are going through great societal change: their kids are growing up or leaving home, and a lot of women reassess their lives at this stage.

It’s the same with the peri-partum period.

Many specialists believe it is the rapid rate of change of hormones, not the actual dose, which can precipitate mood disturbance.