Mental Health

Hormones for Depression in the Menopause

A while back I wrote a post about what you should know about depression in the menopause. It is a topic that I have come to be particularly passionate about since finishing my MSc. My specific topic of focus for my dissertation was whether hormone replacement therapy (HRT) was beneficial for menopausal depression and/or low mood. During my time working on this dissertation, I came across opinions and research which were either 100% pro HRT or 100% against HRT and it is my worry that when people struggling with their mental health during the menopause attend meetings with doctors or specialists to discuss this, they may be forced into a treatment that may not work for them or dissuaded from a treatment that may change their life for the better. I want, with this blog post, to provide a balanced review of the existing research into the treatment of menopausal depression with HRT and to equip you with the knowledge you need when going into this time of your life. I honestly feel that the menopause, and its associated symptoms, is not discussed openly enough, so let’s create some dialogue about it. Nothing is Proven Yet The first point I wish to make clear is that there is currently a lot of confusion and disparity in the HRT for/against menopausal depression research world. In the world of research, there are different levels of evidence. One of the highest forms of evidence in medicine are clinical trials, where a treatment is tested against placebo or against other similar treatments to see which is the most effective. For clinical trials it is important that the studies are blinded meaning that the participants don’t know which treatment they are being given. Unfortunately, there are not many high quality clinical trials for HRT and menopausal depression, in fact I only found a total of 29 from an original 51,000 that matched the criteria I set. Of these 29 studies, each study explored different stages of the menopause, different types of HRT and for different types of mood and depressive symptoms. What this means is it is very difficult to conclude anything. While the studies do overall suggest that HRT may be promising as a treatment for menopausal depression in the future, it is impossible to say this for certain at present. So, to put it bluntly, those who tell you that the only way to treat your mood symptoms in the menopause is through the use of HRT are biased. Different Types of HRT One of the problems with the current body of research is that there are so many different types of hormones and hormone combinations for HRT. There are oestrogen therapies, and within that different types of oestrogen therapies, there are progestins which are sometimes combined with oestrogen therapies, there are testosterone therapies, and tibolone. When there are so many different types of hormones that can be used, and each study explores a different type HRT, it becomes impossible to tell if any one type of HRT is more or less beneficial than another because none of them are being compared. Similarly there are no replication studies, so each study stands by itself, with no other studies backing up their findings. Different Types of Mood Symptoms Another problem to mention just before we get to the evidence for or against HRT is that studies seem to explore different types of mood symptoms, from just general low mood and low quality of life, to depressive symptoms, to clinical depression. Where each study again focuses on something different, it makes it impossible to delineate whether HRT is more or less beneficial for a specific severity of mood or depression experiences. What the Evidence Suggests For Low Mood and Quality of Life Many of those going through the menopause will not experience depression symptoms or clinical levels of depression but may experience lower moods than normal and a reduced quality of life (Blumel et al., 2000). The most common type of hormone therapy used is oestrogen replacement therapy, which can come in many forms and is sometimes combined with a progestin (a synthetic progesterone). Typically, oestrogen therapy comes in the form of oestradiol or conjugated equine oestrogens (CEEs). There is some evidence that both oestradiol and CEEs improve negative moods in the perimenopause (Raz et al., 2016), and when combined with a progestin, two studies documented a beneficial effect of CEEs on mood during the postmenopausal period (Bukulmez, 2001; Gleason et al., 2015). Another type of hormone called Tibolone is a medication displaying mild oestrogenic, progestogenic and androgenic effects. It has also found to be effective for treating low mood however one study found that it was no more effective than oestrogen therapy and one study found that the benefits were also no different to the control group meaning that a group without treatment improved as much as those taking Tibolone (Davis, 2002; Inan et al., 2005; Polisseni et al., 2013). There was one study I found that explored the effect of testosterone therapy on psychological well-being in premenopausal women (Goldstat et al., 2003). In the period prior to the menopause, testosterone declines rapidly to a point where women in their 40s tend to have half the testosterone of women half their age. The study found that testosterone therapy improved general psychological well-being however the study’s primary concern was with low libido which also improved with the testosterone therapy. With results like this it is important to consider that the improvement in libido may have improved well-being rather than the HRT itself. In postmenopausal women however there is some research to suggest that HRT has very little effect on mood or quality of life (Nielsen et al., 2006). In-fact one study noted that an oestradiol+progestin combination actually worsened low mood in women who were switching to a new type of HRT from a different type of HRT (Odmark et al., 2004). Another study found that higher doses of progesterone treatment increased levels of allopregnanolone in the body, and that higher levels of allopregnanolone could deteriorate mood (Andréen et al., 2005). For Depressive Symptoms Mild and moderate experiences of depression are much more common than severe or clinical experiences of depression during the menopause (Zeng et al., 2019). There is again evidence that oestrogen therapy with or without the combination of a progestin is effective for reducing depression symptoms in postmenopausal women (Cagnacci et al., 2004; Gordon et al., 2018; Onalan et al., 2005). There is, however, also evidence to suggest that oestrogen therapy is no better than placebo (Diem et al., 2018; Marinho et al., 2008; Whedon et al., 2017) Tibolone for depressive symptoms was found to be as effective as a CEE+progestin combination in improving depression symptoms (Onalan et al., 2005; Yazici et al., 2003). Interestingly, one study explored the effects of genistein, which is a phytoestrogen. Phytoestrogens are dietary oestrogens that are found in plant-foods. They potentially offer the same benefits of HRT without the potential risks like higher risk of breast, endometrial and ovarian cancer. The study found that genistein, which is commonly found in soy products, improved depression symptoms both after one and two years of administration (Atteritano et al., 2014). While this is a promising avenue for future research, at the moment genistein has very little evidence for this specific purpose. Testosterone is, again, largely understudied in regard to depression symptoms as it is for low mood. One study found that there was an association between testosterone levels and lowered depression symptoms, but this result was only found in Caucasian women and not in African American women (Milman et al., 2015). Another study suggested that balancing testosterone with oestrogen levels may help to reduce depression symptoms but again the research is lacking to a point where no conclusions can be drawn about the use of testosterone for depression symptoms (Rohr, 2002). For Clinical Depression The menopause has been identified as a risk factor for experiencing a first incidence of clinical depression and treatment with oestrogen therapy and tibolone has been associated with not only reduced symptomology but also with remission rates in both the perimenopausal and postmenopausal period (Kulkarni et al., 2018; Rudolph et al., 2004; Schmidt et al., 2000). Where oestrogen therapy really seems to have an impact is where it is used alongside antidepressants. Oestrogen and antidepressants (SSRIs specifically) both respectively seem to effectively treat clinical depression in menopausal women, however when used in combination, the results out-perform the individual treatment results (Amsterdam et al., 1999; Graziottin & Serafini, 2009; Pae et al., 2008; Soares et al., 2003; Westlund Tam & Parry, 2003; Yu et al., 2004; Zanardi et al., 2007). It is not clear at the moment which treatment augments which, but it is a clear finding that oestrogen combined with SSRIs could be a superior treatment for clinical depression in the menopause. Unfortunately, there is a lack of evidence for the use of any other types of HRT for clinical depression in the menopause. Conclusion What this article is not supposed to be is a deterrent from using HRT to manage your mood symptoms. There is plenty of evidence to suggest that in some cases, it can be very beneficial. What this article is supposed to highlight is that the research is far too varied and inconclusive for a doctor to tell you that HRT is either the be-all-end-all solution to your problems, or that you should never go near it. I believe that it is probably the case that the benefits of HRT will be seen on an individual basis. Certain types of HRT will work for one person and won’t work for another. I believe unfortunately, at the moment, it is probably a case of trial and error. If you are struggling with mood symptoms during your menopause, seek out help. It is not uncommon and many women will be experiencing these debilitating symptoms too. Talk to your doctor about your options and if you don’t feel like your doctor takes a balanced view on the treatments available, seek out another doctor. It is all about finding which treatment works for you. You do not have to suffer and you do not have to be alone. I wish you all the best. References Amsterdam, J., Garcia-España, F., Fawcett, J., Quitkin, F., Reimherr, F., Rosenbaum, J., & Beasley, C. (1999). Fluoxetine efficacy in menopausal women with and without estrogen replacement. Journal of Affective Disorders, 55(1), 11–17. https://doi.org/10.1016/S0165-0327(98)00203-1 Andréen, L., Sundström-Poromaa, I., Bixo, M., Andersson, A., Nyberg, S., & Bäckström, T. (2005). 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