Psychiatry and the Menopausal Transition: Clinical Caveats

BRIEF COMMUNICATION

Dr Freeman is a speaker at this year’s PsychCongress in a presentation titled “Menopausal Depression and Premenstrual Mood Dysregulation.” 

The menopausal transition is characterized by sex hormone variability and a vulnerability to depressive symptoms and major depressive episodes. The rate of new-onset major depressive episodes is increased during the menopausal transition, as is the experience of depressive symptoms. The majority of women suffer from hot flashes, or vasomotor symptoms, which range in severity from mild to more severe with an impact on functioning.

The term “perimenopause” refers to the time around this reproductive life cycle transition. More formally, the term “postmenopause” refers to the time 12 months or later after the final menses. Carefully conducted longitudinal studies have demonstrated that perimenopausal women are at higher risk for major depressive episodes than are premenopausal women, and that the risk is associated with hormonal variability.^1,2 It appears that it is not the absolute levels of sex hormones such as estrogen that confer risk, but rather the variability that characterizes the menopausal transition.

Common symptoms other than depression and hot flashes that psychiatrists may frequently encounter include sleep dysregulation, cognitive complaints, fatigue, pain, and anxiety. The symptoms that accompany the menopausal transition are explained by the “estrogen withdrawal theory.”³ This theory can be applied to explain vulnerabilities to depressive symptoms during reproductive hormone variability-premenstrually, postpartum, perimenopause, and at times of fluctuating levels of estrogen and other gonadal hormones.

While the life cycle transition of menopause is characterized by hormonal vulnerability, hormone treatment is not necessarily the only treatment, although it may be used as a primary or adjunctive strategy. Estrogen is known to diminish hot flashes, but the risk-benefit profile is in question, and many women seek to avoid hormone therapies. Notably, there was controversy around the routine use of hormone replacement therapy after the release of findings from the Women’s Health Initiative study.⁴ This study showed that women who received estrogen plus progestin were at a slightly increased risk for coronary heart disease, stroke, pulmonary emboli, and invasive breast cancer. Further, they did not have the preventive health benefits that were widely believed to be associated with long-term hormone therapy.

A major depressive episode in the menopausal transition is treated similarly to an episode that may occur at any other time of life, with the caveat that antidepressants with serotonergic activity, particularly SSRIs and SNRIs, are also effective for the treatment of hot flashes.⁵ Other pharmacological strategies can be used to target hot flashes specifically, such as gabapentin.⁶ Sleep dysregulation associated with the menopausal transition can be specifically targeted with cognitive-behavioral strategies or medications to improve sleep, such as sedating antidepressants or hypnotics.⁷ The Tableserves as a summary of indicators of menopausal transition and menopausal symptoms discussed in this article.

Disclosures:

[[{"type":"media","view_mode":"media_crop","fid":"27444","attributes":{"alt":"","class":"media-image","id":"media_crop_7699358080711","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"2675","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","title":" ","typeof":"foaf:Image"}}]]Dr Freeman is Associate Professor of Psychiatry at Harvard Medical School; Medical Director of CTNI; Director of Clinical Services, Perinatal and Reproductive Psychiatry Program at Massachusetts General Hospital in Boston. She is the Depression Section Coeditor for Psychiatric Times, with George I. Papakostas, MD. Dr Freeman reports that over the past 12 months she has served on advisory boards and/or consulted for Takeda, Lundbeck, Otsuka, Johnson & Johnson, Genentech, and JDS Therapeutics, and she has edited for DSM Nutritionals.

References:

1. Cohen LS, Soares CN, Vitonis AF, et al. Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles. Arch Gen Psychiatry. 2006;63:385-390.
2. Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry. 2006;63:375-382.
3. Schmidt PJ, Nieman L, Danaceau MA, et al. Estrogen replacement in perimenopause-related depression: a preliminary report. Am J Obstet Gynecol. 2000;183:414-420.
4. Rossouw JE, Anderson GL, Prentice RL, et al; Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321-333.
5. Soares CN, Frey BN. Challenges and opportunities to manage depression during the menopausal transition and beyond. Psychiatr Clin North Am. 2010;33:295-308.
6. Pinkerton JV, Kagan R, Portman D, et al; Breeze 3 Investigators. Phase 3 randomized controlled study of gastroretentive gabapentin for the treatment of moderate-to-severe hot flashes in menopause. Menopause. 2014;21:567-573.
7. Joffe H, Massler A, Sharkey KM. Evaluation and management of sleep disturbance during the menopause transition. Semin Reprod Med. 2010;28:404-421.