Should MHT be first line for treating perimenopausal depression? The recent International Menopause Society conference in Melbourne set out to answer this question with a debate between two world leaders in research.

In the affirmative corner, Melbourne’s own Professor Jayashri Kulkarni, a psychiatrist from The Alfred and Monash University. Her opponent, Dr Pauline Maki, PhD, Professor of Psychiatry, Psychology and Obstetrics & Gynecology at the University of Illinois at Chicago. Both women have dedicated years to researching the effects of menopause and hormones on the brain and between them they have almost 700 published papers.

A show of audience hands at the start revealed the majority of delegates were supporters of Professor Kulkarni’s position, and that Professor Maki had her work cut out for her.

Professor Kulkarni argued that the current definitions of depression were inadequate when it came to patients in perimenopause. She said they present differently and the hint was in the name – a depression that’s caused by perimenopause.

“This is a different beast. It’s severe. It’s a type of depression that many women, around perimenopause onset, describe. So that’s if you like, the phenomenology,” Professor Kulkarni said.

She added these women often have no history of previous depression and they often describe a series of specific symptoms including irritability and sometimes rage, loss of confidence, paranoia, anxiety and panic attacks as well as somatic aches and pains, sleep disorders, weight gain and suicidal ideation. She and her colleagues used these symptoms to develop a specific questionnaire for assessing perimenopausal depression called the Meno-D.

Professor Kulkarni went on to argue that depression was a complicated thing and we were now understanding the role of hormones – specifically oestrogen, progesterone and testosterone, and how they affect the brain.

“In the old days, when everything was much more simple, depression was thought to be ‘you’re down in serotonin, you’re down in noradrenaline. So, we’ll just give you this drug called an SSRI. It’ll prop up the serotonin and everything will be roses,’” she said, adding that it “worked in about 40% of people, but it doesn’t work very well in this group.”

What did work, she said, was replacing lost oestrogen and there were studies to back that up.

But do they cut the mustard? Professor Maki, who was a pioneer in the discovery of oestrogen receptors in the brain, argued that unfortunately they don’t.

Yes, she agreed, there are studies that show oestrogen can improve depressive symptoms in some women, but they’re limited. She said there were a total of three RCTs looking at oestrogen and perimenopausal depression; one had 31 participants, another had 45, and the largest had 42 — with follow up ranging from 6 to 12 weeks.

“Let’s look at the quality of the data,” she said. “Goodness. We have 148 women participating in clinical trials to see if estradiol is effective. A whole 148 women. Are we going to practice medicine on 148 women? No, I don’t think so. The follow up period is limited to a maximum of 12 weeks. Is that sufficient? Questions remain about the best progestogen to use, because these trials did not include a progestin.”

“So fewer than 150 people, no progesterone, and 12 weeks of follow up. Are you going to practice medicine on that?” Professor Maki emphasised.”

She went on to argue that studies showed the vast majority of women with depressive symptoms in perimenopause do have a previous history of depressive symptoms and that it’s not the decline in estradiol that’s the problem, but the fluctuations. She cited studies that showed MHT wasn’t effective in treating depression in post-menopausal women, and added that the number of women with severe depression who are vulnerable to fluctuations in perimenopause is somewhere between 3-11% – “so it’s relatively rare,” and she posed the question of how do you identify that person in a clinical setting?

“It’s too difficult. … How are you in the clinical settings supposed to be understanding who those women are?”

She added that data on depression in women who were menopausal due to surgery also showed that MHT wasn’t effective, but the role of SSRIs was well established.

“Depression is too serious of an issue to get wrong,” she said. “The World Health Organization reported that depressive and anxiety disorders were among the top 10 leading causes of disability worldwide for females, but not for males, and the global burden of disease in males and females is considerably greater in women…We need to use the evidence base for treating depression the way that we would for other aspects of menopause,” Professor Maki said.

“So, is oestrogen a first line therapy for perimenopausal women? No, though it can be a very good thing to have in the toolbox for some.”

Did the audience agree? A show of hands showed it was a close call but some in the audience were undecided.

There was, however, agreement on the need for more research – and that both SSRIs and MHT can often be used hand in hand.

You can watch the full debate for yourself on the ‘on demand’ section of the IMS conference website here (if you didn’t attend the conference, you can purchase credits to view it).