In our over three decades of helping women with hormonal imbalances, we have seen our fair share of patients who are considered “at risk” for depression. One such patient is the middle aged woman who is finishing with the menopausal part of her life and entering post-menopause. Here this woman may see a continuation or acceleration of symptoms related to estrogen deficiency or hormonal imbalance. Many of the body’s naturally occurring hormones, including or in some women, especially estrogen decline with age. This decline can lead to mood swings; irregular heartbeat; night sweats; hot flashes, and depression, to name just a few of the challenges a woman may face. More symptoms were outlined in a May 2021 paper in the journal BMC Womens Health (1) that could possibly be related to hormonal deficiency.
“Postmenopausal women with higher age and lower physical activity had a greater possibility of having mild and moderate depression. Lower physical activity was also correlated with a greater possibility of having medium upward to severe trait anxiety symptoms. Postmenopausal women with higher (body mass index) BMI and body fat mass (BFM) had more severe menopause-related and trait anxiety symptoms. Women with lower lean body mass (LBM) and soft lean mass (SLM) had more severe depressive symptoms.”
Older woman with lower physical activity, higher body mass index and body fat mass had more severe menopause-related and trait anxiety symptoms.
There is some controversy in making what seems to be a common sense connection between hormonal deficiency, estrogen and depression, mood and the numbers symptoms we just listed.
This controversy is discussed in the April 2021 journal Archives of women’s mental health.(2) In this paper the researchers examined previously reported studies discussing the relationship of obesity and depression in women. What they found was “few articles considered confounding factors related to female hormones” and none of the articles focused on factors responsible for the obesity-depression relationship in women. Future studies should focus on trying to understand how the female sex and normal hormonal variations influence these conditions.
Estrogen therapy for women with mood and depression disorders
Researchers and doctors have long explored the problems of estrogen deficiency and mood and depressive disorders in menopausal and postmenapusal disorders. We are going to examine some of the beneficial findings of this research.
Women’s “window of vulnerability” . . . estrogen plays an important role in mood and cognitive regulation
In the medical journal Menopause (3), a paper titled: “Mood Disorders in Midlife Women: Understanding the Critical Window and Its Clinical Implications,” Canadian researcher Claudio N Soares offered these observations:
“Menopausal transition and early postmenopausal years have been described as a “window of vulnerability” for the development of depressive symptoms or depression (new or recurrent) in some women. . . Despite evidence of a critical window for new onset of depression, a prior depressive episode (particularly if related to reproductive events) remains the strongest predictor of mood symptoms or depression during midlife years. Vasomotor symptoms, anxiety, and other health-related issues also modulate the risk for depression. Mechanistically, estrogen plays an important role in mood and cognitive regulation.”
Estrogen can be beneficial
Dr Jenifer Sassarini of the University of Glasgow described the difficulty in understanding and treating depression in menopausal and post-menopausal women. She wrote in the journal Maturitas, (4) “despite the challenges these difficulties represent, empirical evidence (what the doctors and patients see outside of clinical studies) suggests that estrogen therapy for women with mood and depression disorders is beneficial and should be considered for patients.”
The impact of estrogen on neurotransmitters and brain chemicals implicated in clinical depression.
A doctors’ ability to explain the complex role of sex hormones, such as estrogen and their delicate function in helping to balance levels of neurotransmitters, brain chemicals implicated in clinical depression can help a patient understand the complexity of her hormone deficiency and her mood and depression problems.Depression has been linked to problems or imbalances in the brain with regard to the neurotransmitters not only of serotonin, but of epinephrine, norepinephrine, GABA and dopamine.
At the Magaziner Center for Wellness, we analyze the urine to test the levels of these neurotransmitters, and use blood tests to look at levels of key amino acids. We also review the levels of fatty acids, namely Omega-3 fatty acids, and test for deficiencies in trace minerals such as intracellular magnesium and zinc, and vitamins including B-12, as low levels of any of these have been linked to depression. This comprehensive analysis enables us to treat the disorder using nutritional supplementation in support of hormonal supplementation.
Depression is just one of many symptoms seen in estrogen deficient women
There are so many symptoms related to estrogen deficiency that depression can be lost among as a primary concern. Here for example are current guidelines for doctors in evaluation the need for estrogen replacement therapy. These guidelines are for synthetic hormones. The difference between synthetic and bio-identical hormones will be explained below.
The 2017 Hormone Therapy Position Statement of The North American Menopause Society (NAMS), the current recommendations used by doctors who prescribe synthetic estrogens, gave these treatment suggestions:
Hormone therapy remains the most effective treatment for vasomotor symptoms (night sweats, hot flashes, flushes, vaginal dryness and related disorders) and the genitourinary syndrome of menopause and has been shown to prevent bone loss and fracture.
The risks of Hormone therapy (remember this is synthetic hormones) differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.
Treatment should be individualized to identify the most appropriate Hormone therapy type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing hormone therapy.
For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome vasomotor symptoms and for those at elevated risk for bone loss or fracture.
For women who initiate hormone therapy more than 10 or 20 years from menopause onset or are aged 60 years or older, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia.
In regard to depression, the guidelines say this: “For postmenopausal women without clinical depression, evidence is mixed concerning the effects of hormone therapy on mood, with
small, short-term trials suggesting that hormone therapy improves mood, whereas others showed no change. Postmenopausal women with a history of perimenopause-related depression responsive to hormone therapy may experience a recurrence of depressive symptoms after estradiol withdrawal.”(5)
At the Magaziner Center for Wellness, we use bio-identical hormones (BHRT). Bio-identical hormones are different than synthetic hormones because they are structurally and chemically the same as the three estrogens naturally produced by the body – Estriol, Estradiol and Estrone and natural progesterone, testosterone and others, depending on the needs of the patient. Synthetic hormones – namely conjugated estrogens feature a manipulated form of the three estrogens while Medroxyprogesterone Acetate (MPA), which is found in Provera, is a synthetic form of progesterone.
The body responds to and metabolizes synthetic hormones differently than bio-identical hormones. Bio-identical hormones are far safer and more effective than synthetics and, therefore, have grown in use. At the Magaziner Center for Wellness, we have been treating patients for more than 25 years with BHRT. Each is compounded by pharmacists – meaning they are handmade using a mortar and pestle – so that they are customized for each patient based on the strength needed by each individual according to her needs and wants.
Before formulating a treatment plan, the doctors at the Magaziner Center for Wellness analyze each patient individually using 24 hour urine specimens and comprehensive blood work. We look at the metabolites of estrogen in a woman’s body, as certain metabolites can increase the risk of breast or gynecological cancers. We also look at both thyroid and adrenal function. We rarely use saliva tests as they are not comprehensive enough to give information about hormone metabolites and to ascertain the best course of treatment for a patient.
We use a self-scoring system each time a patient comes in so that we can further customize and assess the success of her treatment as it progresses. This allows us to tweak the dosages so that we can optimize the patient’s results.
The decision to use estrogen therapy in instances of depression are complex and require a consultation with our doctors.
1 Barghandan N, Dolatkhah N, Eslamian F, Ghafarifar N, Hashemian M. Association of depression, anxiety and menopausal-related symptoms with demographic, anthropometric and body composition indices in healthy postmenopausal women. BMC women’s health. 2021 Dec;21(1):1-2.
2 Baldini I, Casagrande BP, Estadella D. Depression and obesity among females, are sex specificities considered?. Archives of women’s mental health. 2021 Apr 20:1-6.
3 Soares CN. Mood disorders in midlife women: understanding the critical window and its clinical implications. Menopause. 2014 Feb 1;21(2):198-206.
4 Sassarini DJ. Depression in midlife women. Maturitas. 2016 Dec;94:149-154. doi: 10.1016/j.maturitas.2016.09.004. Epub 2016 Sep 16.
5 The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728‐753. doi:10.1097/GME.0000000000000921