January 10, 2018

expert reaction to HRT preventing depression in women around the menopause

Publishing in JAMA Psychiatry, researchers report results from a 12-month randomised clinical trial of estrogen plus progestin hormone therapy vs placebo for the prevention of depressive symptoms in non-depressed perimenopausal and early postmenopausal women.

Prof. Allan Young, Director, Centre for Affective Disorders, King’s College London’s Institute of Psychiatry, Psychology & Neuroscience, said:

“These results aren’t that surprising, as there is a long back story implicating hormones in depression, but this is high quality research backed up by good data.

“If these interesting preliminary data are replicated then this could potentially have big implications for the relevant patient group. For now, this should set the scene for further research examining the risks and benefits of hormonal approaches for the prevention and treatment of depression in this patient group.”

Prof. Saffron Whitehead, Emeritus Professor of Endocrinology at St George’s University of London and Society for Endocrinology member, said:

“This study examined the effects of oestrogen patches (transdermal delivery) plus intermittent micronised progesterone pills on the effects of depression in premenopausal and early menopausal women. This is a transitional period in a woman’s reproductive life which is linked to declining oestrogen levels and loss of ovarian function. It normally occurs around the age of 50 and is associated with depression. However, this stage of life is often linked with changing social and emotional factors, such as children leaving home, a feeling of getting older, declining sexual libido and, of course, loss of fertility.  Thus, the menopausal symptoms are not only due to the body adapting to declining oestrogens, but to other stress factors, both of which can contribute to depression.

“Over a hundred women completed this study, 63 received hormone therapy and 69 received placebo (control group). Those receiving hormone therapy had significantly fewer depressive episodes compared to the control group, and this was more effective in women in their early menopausal period -when oestrogen levels are still showing peaks and troughs- compared to women who were in their late menopausal/early menopause -when oestrogen levels are low but not fluctuating. This may be because hormone therapy in the early menopausal period maintains a more steady level of oestrogen. In addition, it was found that oestrogen treatment had greater benefits in women who had higher stressful incidents in relation to those who had less stressful incidents.

“Whilst this is an interesting preliminary study and may be considered as a treatment option for depression in menopausal women, the treatment increased the incidence of vaginal bleeding (spotting, prolonged bleeding). Additionally, the benefits of hormone replacement therapy need to be weighed against the risks.”

Dr Martin Blomberg-Jensen, Senior Researcher at Righospitalet (Denmark), Group Leader and Lecturer at Harvard University, and Society for Endocrinology member, said:

“This novel study shows that transdermal hormonal therapy (estradiol and progesterone) lowers the proportion of postmenopausal women with depressive symptoms. Depressive symptoms and disorders are more frequent in women during the menopause transition and this study indicates a beneficial effect of hormonal replacement therapy for women during this phase. This adds to the long discussion about using hormone replacement therapy in some postmenopausal women when benefits outweighs risks.

“The main limitation of the study is that data are not generalizable for most postmenopausal women, as only 10% of the screened population were included. This implies that this effect has only been found in a small subgroup of women. Moreover, the link to hormonal replacement was not corroborated by measuring serum level of hormones during and after intervention, which could have supported the data tremendously.”

Prof. Tony Cleare, Professor of Psychopharmacology & Affective Disorders, King’s College London’s Institute of Psychiatry, Psychology & Neuroscience, said:

“This a well conducted trial, albeit in a relatively small number of women.

“Essentially, HRT reduced the proportion of women who experienced significant mood symptoms from about 1-in-3 to about 1-in-6.  This was especially seen in women at the beginning of menopause, and in those experiencing other life stresses. The effect occurred irrespective of how well HRT controlled other menopausal symptoms such as hot flushes.

“Unfortunately, this beneficial effect comes at the expense of worsened menstrual bleeding in those taking HRT.

“HRT is already recommended in the UK by NICE to treat symptoms of low mood during the menopause, so this research adds to the evidence by showing HRT can also prevent mood symptoms.  Nevertheless, the decision to use HRT should always be based on a woman’s individual circumstances and preferences, weighing up the likely risks and benefits.”

* ‘Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention of Depressive Symptoms in the Menopause Transition – A Randomized Clinical Trial’ by Gordon et al. published in JAMA Psychiatry on Wednesday 10^th January.

Declared interests

Prof. Young: “I have no conflicts of interest”

Prof. Whitehead: “I declare I have no interests to disclose”

Dr Blomberg-Jensen: No interests declared

Prof. Cleare: “No declarations relevant to this topic”