|Ahead of print publication
Depression: Unraveling the gender differences
Heena Merchant1, Prerna Balkrihsen Khar2
1 Department of Psychiatry, LTMMC and GH, LTMMC, Mumbai, Maharashtra, India
2 Department of Psychiatry, TNMC and BYL Nair Charitable Hospital, Mumbai, Maharashtra, India
|Date of Submission||20-Jan-2021|
|Date of Decision||22-Jan-2021|
|Date of Acceptance||10-Feb-2021|
|Date of Web Publication||11-Mar-2021|
Prerna Balkrihsen Khar,
TNMC and BYL Nair Charitable Hospital, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Depression in men and women presents differently and there are various factors governing this. This article aims to elucidate these differences so that the management approach can be adopted as required and the morbidity be reduced.
Keywords: Depression, gender differences, women
| Introduction|| |
Depression has now become one of the leading causes of the global burden of disease and will lead the charts by 2030. In 2010, it was the second leading cause of years lived with disability. It is the leading cause of disease burden in a woman already. This article aims at understanding how and why does depression present differently in women as compared to men.
| Prevalence|| |
Depression is the leading cause of disease-related disability in women. Studies have shown that the lifetime prevalence of a major depressive disorder in women (21.3%) is almost twice as that in men (12.7%). Sex differences in prevalence first appear around the age of 10 years and persist until midlife, after which they disappear. Unfortunately, women have the greatest risk for developing depressive disorders during their child-bearing years.
| Difference between the Sexes: Are Men are from Mars, Women from Venus?|| |
Out of the symptoms associated with depression, women are more likely to have sexual disturbances/loss of libido, somatic difficulties, and metabolic changes. On the other hand, men tend to have alcohol or other drug use and risk-taking behavior., Comorbid anxiety disorders are more common in women as compared to men.
Are women more susceptible?
Women are more likely than men to dwell on problems due to which transient dysphoric symptoms develop into depressive episodes (Rumination Theory). A ruminative response style, the tendency to passively and repetitively analyze one's distress, problems, and concerns, without taking actions increases depressive tendencies in women. Women tend to present with internalizing symptoms and men with externalizing symptoms. In a study of dizygotic twins, women displayed more sensitivity to interpersonal relationships, whereas men displayed more sensitivity to career and goal-oriented factors. Genetic factors play a stronger role in women as compared to men.
Role of puberty
Psychosocial adversities, such as a poor parent–child relationship and childhood sexual abuse, predict early maturation in girls but not in boys. This clearly shows that female pubertal transition seems to be more responsive to adverse environments. Compared to boys, early sexual maturation in girls is linked with more severe and longer-lasting psychopathology, especially with respect to depression.
The wave of hormones
Depression in women has been linked to the reproductive cycle. Premenstrual syndrome (PMS), regularly recurs during the luteal phase of each menstrual (ovarian) cycle. This is evident by the absence of PMS before puberty, in pregnancy, and after menopause and thus supports the theory that cyclical ovarian activity is important.
Other reproductive events include postpartum depression and the “baby blues.” The relationship between depression and the reproductive years was described by Soares as a “window of vulnerability” This window may be influenced by changes in metabolism, sexuality, lifestyle, and overall health.,
Given the protective role of estrogen against developing depression, why then do men, who lack estrogen, have lower rates of depression compared to women?
Research has shown that in the male brain, testosterone is converted into estrogen by endogenous aromatase (CYP19). Estrogen mediates protective actions through estrogen receptors expressed throughout the male brain. The presence of androgen receptors in men may confer protection, for example in hippocampal neurons. Since testosterone does not cycle in men as estrogen does in women, there may be a more consistent protection in men.
Differences in brain circuitry
Men have sexually dimorphic brain nuclei, particularly in the hypothalamus, which also explains lower susceptibility to develop depression.
Stress response is attenuated in women as compared to men. An evolutionary hypothesis for this is the pressure to protect the fetus from the adverse effects of maternal stress. This blunted Hypothalamo-pituitary-adrenal (HPA) axis response to stress puts women at a greater risk to develop depressive disorders compared to men. Hypoactivation of the HPA axis is seen in premenstrual dysphoric disorder, which contributes to increased premenstrual symptoms.
The expression of the enzyme required for Gamma-amino-butyric acid (GABA) synthesis is sexually dimorphic in discrete regions of the hypothalamus, and also in the amygdala and the hippocampus, GABA is sensitive to estradiol during the sensitive period of steroid-mediated brain sexual differentiation. Brain-born estradiol rapidly blocks GABA release in females but not in males due to the generation of inositol triphosphate and activation of its receptor (IP3R). The complex of ERα, glutamate receptor, and IP3R are present in both sexes but are regulated by estradiol only in females.
Influence of women's social role
Stress levels are higher in women. In addition to this, the fulfillment of female sex roles is reportedly less satisfying than male sex roles. Gender-based discrimination at workplace, home, and other settings also contributes to the development of depressive symptoms in women.
The mid-life crises
Postmenopausal women often have to face various stressors which may contribute to the development of depression. These include children leaving the home, change in family structure, retirement, and increased caregiver burden with respect to grandchildren, parents, and in-laws. Menopause in itself is a risk factor for depression, more so in women who experience vasomotor symptoms. The Harvard Study of Moods and Cycles reported a twofold increased risk of depression in women who entered perimenopause compared to those who were premenopausal.
The daily production rate of estrogen (which has antidepressant properties) falls nearly eightfold to an output of approximately 48 micrograms per 24 h during menopause. This could also explain the emergence of depressive symptoms during the perimenopausal stage. In addition, anxiety symptoms were more common in postmenopausal women.
Oral contraceptive pills – The double-edged sword
Worldwide, a large number of women rely on oral contraceptive pills (OCPs) to control their fertility. The addition of progesterone to hormone therapy has been has implicated as causative to induce adverse mood effects. Various mechanisms have been postulated, namely:
- The action of progesterone metabolites on the γ-aminobutyric acid A receptor complex
- Levels of neuroactive metabolites of progesterone increase during the luteal phase of the menstrual cycle in and some experience negative mood symptoms due to this
- External progestins, more than natural progesterone, increase levels of monoamine oxidase, which degrades serotonin concentrations and thus leads to depression and irritability
- Clinical studies have indicated that changes in estrogen levels (due to OCPs) may trigger depressive episodes among women who have a risk for depression.
In a study done to assess the use of antidepressants in women using OCPs, it was found that when the use of oral contraceptives that combined levonorgestrel and 30–40 μg of ethinyl estradiol constituted the reference group, a significantly higher rate of antidepressant use was found among women who used combined oral contraceptives with cyproterone acetate, natural estrogen with dienogest, and a patch or a vaginal ring.
| Conclusion|| |
Given the various factors which determine the onset and progression of depression in women, it is important for the treating team to keep this in mind with regard to management. Psychosocial factors which play a very important role in depression in women need to be addressed, as their neglect can lead to recurrence of symptoms.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Cavanagh A, Wilson CJ, Kavanagh DJ, Caputi P. Differences in the expression of symptoms in men versus women with depression: A systematic review and meta-analysis. Harv Rev Psychiatry 2017;25:29-38.
Noble RE. Depression in women. Metab Clin Exp 2005;54:49-52.
Kuehner C. Why is depression more common among women than among men? Lancet Psychiatry 2017;4:146-58.
Kessler RC. Epidemiology of women and depression. J Affect Disord 2003;74:5-13.
Albert PR. Why is depression more prevalent in women? J Psychiatry Neurosci 2015;40:219.
Sassarini J. Depression in midlife women. Maturitas 2016;94:149-54.
Chen LC, Hsu JW, Huang KL, Bai YM, Su TP, Li CT, <Italic>et al</Italic>. Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study. J Affect Disord 2016;190:282-5.
Perrot-Sinal TS, Davis AM, Gregerson KA, Kao JP, McCarthy MM. Estradiol enhances excitatory gammabutyric acid-mediated calcium signaling in neonatal hypothalamic neurons. Endocrinology 2001;142:2238-43.
Tabatadze N, Huang G, May RM, Jain A, Woolley CS. Sex differences in molecular signaling at inhibitory synapses in the hippocampus. J Neurosci 2015;35:11252-65.
Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL. Risk for new onset of depression during the menopausal transition: The Harvard study of moods and cycles. Arch Gen Psychiatry 2006;63:385-90.
Mulhall S, Andel R, Anstey KJ. Variation in symptoms of depression and anxiety in midlife women by menopausal status. Maturitas 2018;108:7-12.
Skovlund CW, Mørch LS, Kessing LV, Lidegaard Ø. Association of hormonal contraception with depression. JAMA Psychiatry 2016;73:1154-62.