Depressive and anxiety disorders have a lifetime risk of 20-26% in women and 8-12% in men. Cultural and psychological variables relating to the role of women may explain some of this difference. Documented risk factors have included childhood trauma/loss, unhealthy coping styles, limited support systems and conflicts in gender roles. The struggle to excel in multiple roles as a wife, mother, friend and sister while working two jobs would be an example of the latter.
However, this increased risk has been demonstrated in diverse countries and cultures, suggesting that biological variables are significant in addition to cultural and psychological contributions. Furthermore, depression has been associated more with hormonal transitional events such as menarche, pregnancy, contraceptive use, menstrual cycles, miscarriage, total hysterectomy,
perimenopause/menopause and hormone replacement therapies. Thus, much of the biological research focus has centered on estrogen and progesterone relationships with known neurotransmitters in the brain.
Estrogen and progesterone should be thought of as brain hormones, not just relevant to ovarian, uterine or bone issues. Receptors for both hormones are found in the amygdala, hippocampus, cingulate cortex, locus ceruleus and rapha nuclei. These areas of the brain comprise critical components of the limbic system that managethe neurotransmitters serotonin, norepinephrine and dopamine.
Deficiencies in these neurotransmitters have been associated with a variety of mood and anxiety disorders. Estrogen has been shown to increase neurotransmitter levels, stimulate nerve growth factors and promote neuronal communication via second messenger systems. In other words, estrogen can function as a “fertilizer” of sorts for brain function for many women under normal circumstances. However, normal “circumstances” can become complicated.
Under normal circumstances, estrogen acts as a substantial multiplier of serotonin function. Thus women would not need as much serotonin as men in order to get the same benefit due to this amplification from estrogen. In fact, women do synthesize serotonin at much lower rates than men, as a toxic reaction (serotonin toxicity syndrome) could occur if women made serotonin at the same rate as men. This is all fine and good as long as one maintained a significant estrogen level for amplification purposes.
In reality, estrogen, progesterone and other hormone levels fluctuate under normal conditions every month to allow for maximum fertility opportunities. Thus, there would be times when estrogen levels are higher in the first half of the month and decline toward to end of the month. Estrogen levels would also be low during other hormonal transitional periods such as postpartum and perimenopause/menopause.
The amplification would be lost then and the individual’s serotonin system would have to speed up to compensate. The ability to speed up serotonin and other neurotransmitter functions is felt to be under genetic control. Thus, the ability to accelerate serotonin function in response to changes in estrogen function could be impacted by genetic wiring. Someone with a strong family history of depression, anxiety disorder, eating disorder or alcoholism may not be able to speed up their serotonin production enough to compensate for the lack of amplification and become symptomatic.
Estrogen was used as a treatment for depression in the distant past because of these issues. This was abandoned with the Women’s Health Initiative study in 2002—better known as the “prempro study.” This study sought to demonstrate the types of benefits that were afforded menopausal women who took hormone replacement therapy with a combination estrogen/progesterone treatment—prempro. The study demonstrated a higher risk of cardiac disease, stroke, venous thromboembolism and breast cancer in the women treated with prempro. The prempro patients had less colorectal cancer and fewer hip fractures.Take help from telephone therapist .
However, this study raised a number of questions about hormone replacement therapy that has led to this therapy no longer ranking as a good first line, long-term treatment. Antidepressants continue to have an important therapeutic role in female depressive states along with diet, exercise, proper sleep, stress management, psychotherapy and the most commonly used “complimentary and alternative therapy”—prayer.
