A controversial study has found that hormone replacement therapy (HRT) may carry a risk of depression.
Researchers in Denmark have monitored nearly 800,000 menopausal women for more than a decade.
Women taking HRT were twice as likely to develop depression as women not taking the pills, patches, and gels.
The results also showed that the risk was higher in the first year after HRT was prescribed and among women aged 45 to 50 years. But those taking vaginal estrogen were not at greater risk, the data concluded.
However, independent experts today criticized the study, which was published in a major journal.
Researchers in Denmark have monitored nearly 800,000 middle-aged women for more than a decade. They found that those taking HRT were twice as likely to develop depression, compared to those not taking the tablets, patches, and gels.
Leading scientists who were not involved in the research insisted that it was impossible for the study to rule that HRT causes depression because of how it was done.
The study, in JAMA Network Open, was observational, meaning it monitored patients without controlling groups that received HRT.
This is compared to gold standard placebo-controlled trials, which allow researchers to separate the effects of a drug in very similar groups.
Experts have also argued that women may become depressed due to severe symptoms of “change.”
Or the scientists explained that women with severe mental health problems were given HRT to see if it boosted their mood before they were diagnosed with depression.
What is the dish?
Menopause occurs when your period naturally stops and you are no longer able to conceive naturally.
It’s a normal part of aging and usually occurs between the ages of 45 and 55 when a woman’s estrogen levels drop.
Eight out of 10 women will experience symptoms of menopause including hot flashes, night sweats, vaginal dryness, difficulty sleeping, low mood or anxiety, and memory problems.
Women are advised to see their GP if their symptoms are difficult to control.
Treatments that doctors can provide include hormone replacement therapy, such as tablets, skin patches, and gels that replace estrogen.
Menopause is when a woman’s menstrual cycle stops – usually between the ages of 45 and 55 – and it’s a normal part of aging.
It is caused by a decrease in the levels of hormones, such as estrogen.
About seven in 10 women experience symptoms that can be severe and disrupt daily life.
These include mental health issues, such as anxiety, mood swings, and brain fog, which can last for months or years and may change over time.
Menopause can also cause physical symptoms, including hot flashes, sleep difficulties, heart palpitations, headaches, muscle aches, and vaginal dryness.
HRT — which some women describe as a lifeline — can help relieve these symptoms by replacing lost hormones.
Nearly two million women in England were prescribed HRT in 2021/22, an increase of nearly a third year on year. More than four in 10 postmenopausal women in the United States take these medications.
Some small studies, each with fewer than 200 participants, have linked the drugs to an increased risk of depression.
Researchers at the Center for Clinical Research and Prevention in Copenhagen set out to examine the link.
They studied data on 825,238 women in Denmark, contained in the Danish National Patient Registry database, who reached the age of 45 between 1995 and 2015.
The team, led by Dr. Mary and Yum Andersen, monitored the women for an average of 11 years, recording all HRT prescriptions and depression diagnoses.
About 189,821 postmenopausal women were treated, usually by age 55, and went on to replace about 33 prescriptions, on average.
Meanwhile, 13,069 cases of depression were diagnosed.
Nearly two million women in England with hot flashes, night sweats and mood swings were prescribed hormone replacement therapy (HRT) in the year to March 2022 (black line). The number is up by nearly a third from the previous year, when 1.5 million women were prescribed pills, skin patches, and gels to control menopausal symptoms. Meanwhile, nearly 8 million HRT items were phased out (blue line), up 35 percent year-over-year.
The graph shows the number of HRT prescriptions per month in England (blue line) and the number of patients receiving them between July 2020 and June 2022. About 870,000 HRT products were prescribed in June 2022. This was an increase of 270,000 (45.1%) from 600,000 Item in June 2021
The graph shows the number of patients in England who received HRT prescriptions by age. The most common group to receive HRT prescriptions in 2021/22 was patients aged 50-54 years with an estimated 437,000 patients identified, 22.7 percent of all patients
Some medications are categorized as systemic HRT – those that tend to contain a higher dose of hormones and come in pill, patch, ring, gel and cream form.
It also included findings on locally given HRT, which are creams that are placed directly into the vagina.
The results showed that rates of depression were higher among women after they started taking HRT, compared to non-users.
Overall, the risk was highest in the first year after the women started taking the hormones, when HRT users were 72 percent more likely to develop depression.
But the risk was “particularly high” in the first year the women took HRT — estrogen alone or a combination of estrogen and progestin — when rates of depression doubled.
In addition, women who were prescribed medication for menopause between the ages of 48 and 50 were 50 percent more likely to develop depression, dropping to 13 percent for those ages 51 to 53.
However, locally given HRT was not associated with depression among the women.
And those who took this version between the ages of 54 and 56 were actually 20 percent less likely to develop depression than those who didn’t take the treatment.
Dr. Wom Andersen and his team said their findings are based on a large group of women who were followed for up to 22 years and include rigorous data on HRT use.
But they note that menopause itself increases the risk of depression, which may explain some cases among HRT users.
They wrote that HRT users may be more likely to develop depression if doctors assume that their depressive symptoms date back to menopause and give them HRT.
The team concluded that the findings suggest that the use of HRT during menopause is associated with the risk of a subsequent diagnosis of depression.
“Locally given HRT is not associated with depression risk but is also associated with a potentially lower risk for women older than 54 years, and therefore may be recommended where appropriate.”
However, Professor Ciara McCabe, a neuroscientist at the University of Reading who was not involved in the study, said many women start taking HRT “specifically because of negative changes in their mood”.
This fit with the finding that rates of depression among HRT users were “highest after initiation and then gradually declining,” she said.
If HRT is causing depression, I wonder why depression gradually recedes with continued HRT use. Professor McCabe added.
Prof David Curtis, of University College London’s Institute of Genetics and not involved in the study, said the finding “may be because HRT increases the risk of depression”.
But he noted that it may also be due to women with severe menopausal symptoms, more likely to be prescribed HRT but also more likely to develop depression.
“Alternatively, depressed women may complain of worsening menopausal symptoms and be prescribed HRT, but only later are they diagnosed with depression in hospital,” Professor Curtis explained.
He added, “Overall, I don’t think the study can shed light on whether or not HRT has any effect on depression risk.”