As the body ages, changes in the production of hormones occur. The period when a woman's body begins the transition to menopause is called perimenopause. Women usually enter perimenopause in their 40s and the following changes can occur:
- periods become irregular -- they become shorter, longer, lighter or heavier
- some symptoms associated with menopause, such as hot flashes, difficulty falling asleep or staying asleep, vaginal dryness and so on
Most research suggests that HIV-negative women who undergo perimenopause do so without experiencing mood disorders. However, some studies have found that women transitioning toward menopause have an increased risk for depression. This increased risk can occur even among women who have no history of mood disorders such as depression.
Focus on HIV
A team of researchers in the U.S. enrolled HIV-positive women and women at high risk of HIV infection and found that, regardless of HIV status, women undergoing perimenopause were at increased risk for experiencing symptoms of depression. In turn, the depression experienced by HIV-positive women affected their ability to take potent combination therapy for HIV (commonly called ART or HAART) exactly as directed. The research team encourages doctors and nurses to screen their female HIV-positive patients who are experiencing changes in their monthly cycles for depression and to offer them treatment if it is present.
The research team, part of the Women's Interagency HIV study (WIHS), enrolled women in 1994 to 1995 and again between 2001 and 2002 in the following American cities:
- Los Angeles
- San Francisco
- Washington DC
The researchers recruited HIV-positive and HIV-negative women of similar age, ethnicity, level of education and HIV risk factors (including injection of street drugs).
Between April 2007 and April 2008 the WIHS team incorporated surveys about menopause and mood. As part of the overall WIHS, every six months women were interviewed, underwent physical examinations and gave blood and other fluids for analysis.
For their study on menopause, researchers focused their analyses on 835 HIV-positive women and compared them to 335 HIV-negative women.
The WIHS team used the following terms and definitions:
- premenopause: "[periods] in the past three months with no changes in regularity"
- early perimenopause: "[periods] in the past three months with changes in regularity"
- late perimenopause: "no [periods] within the past three months but some menstrual bleeding within the past 12 months"
- post-menopausal: "no [periods] within the past 12 months"
The average profile of HIV-positive women when they entered the menopause sub-study was as follows:
- age: 45 years
- menopause status: premenopause 53%; early perimenopause 14%; late perimenopause 5%; post-menopausal 28%
- currently with a partner: 26%
- unemployed: 58%
- past substance use (crack, cocaine or heroin): 64%; "heavy alcohol" use: 32%
- CD4+ cell counts: more than 500 cells: 42%; between 200 and 50 cells: 42%; less than 200 cells: 16%
- proportion with a viral load less than 80 copies/ml: 50%
- proportion taking ART: 63%
- proportion of ART users taking 95% of doses as directed: 75%
- hepatitis C virus (HCV) infection: 35%
Results -- Depression
Rates of depression were the same (38%) among HIV-positive and HIV-negative women.
The distribution of depression by stage of menopause (regardless of HIV status) was as follows:
- premenopause: 33%
- early perimenopause: 47%
- late perimenopause: 42%
- post-menopause: 43%
Taking many biological and social factors into consideration, the researchers found that women undergoing early perimenopause, regardless of HIV status, had the most severe symptoms of depression. This was also the case when researchers restricted their analysis to HIV-positive women.
Here are some other findings:
- women who had less than 200 CD4+ cells reported more severe symptoms of depression compared to women with higher cell counts
- women who took ART exactly as directed had a lower risk of depression
- women not taking ART were four times as likely to have increased symptoms of depression compared to women who took ART
Bear in Mind
The researchers are not certain why symptoms of depression were more severe in perimenopause. However, the WIHS team is conducting long-term research, monitoring the impact of changing cycles on the health of HIV-positive women.
Reconsidering Hormone Therapy
A Danish clinical trial monitoring women who received hormone therapy was recently completed. In that study, Danish researchers recruited 1,006 HIV-negative women around the age of 50 and randomly assigned half to receive hormone therapy. The randomized phase of the trial lasted for 10 years. After this, the women were monitored for six more years, for a total of 16 years of observation. The research team found a reduced risk of death without an increased risk for heart attack or cancer among the women who received hormone therapy compared to those who did not. This beneficial effect occurred during the first 10 years of the study and was maintained. This finding was somewhat surprising because past randomized controlled trials of hormone therapy have not found such therapy to be beneficial; in fact, hormone therapy was associated with an increased risk of harm (heart attacks, stroke, cancer).
Also, researchers have recently completed re-analyses of previous clinical trials of hormone therapy for women who were undergoing menopause. Those re-analyses suggest that hormone therapy may be safer than previously thought when restricted only to women who are just entering menopause, who are relatively young (around the age of 50) and who are otherwise in good health.
Both the Danish study and the re-analyses have prompted renewed interest and debate about the safety of hormone therapy for women. Some researchers are now suggesting that hormone therapy might be appropriate when started in the early stages of menopause. However, it will take months, perhaps years, for this debate to be settled, as doctors and patients weigh the risk and benefits of hormone therapy.
Hormones and HIV -- Caution Needed
Note that nearly all studies about intervening with estrogen (and other hormones and therapies) to treat mood disorders that can occur during the menopause transition have enrolled generally healthy HIV-negative women.
The WIHS team warned that estrogen-based therapies are known to cause an increased risk for unnecessary blood clots, which can lead to a heart attack or stroke. Infection with HIV in people and infection with the closely related virus SIV in susceptible monkeys is also associated with an increased risk for cardiovascular disease. Therefore, caution is needed when conducting clinical trials of or prescribing estrogen-based therapy in HIV-positive women who are in the transition to menopause.
- Maki PM, Rubin LH, Cohen M, et al. Depressive symptoms are increased in the early perimenopausal stage in ethnically diverse human immunodeficiency virus-infected and human immunodeficiency virus-uninfected women. Menopause. 2012; in press.
- Schierbeck LL, Rejnmark L, Tofteng CL, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012; in press.
- Hodis HN, Collins P, Mack WJ, et al. The timing hypothesis for coronary heart disease prevention with hormone therapy: past, present and future in perspective. Climacteric. 2012 Jun;15(3):217-28.
- Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. Journal of the American Medical Association. 2007 Apr 4;297(13):1465-77.
- Manson JE, Bassuk SS. Chapter 348. The Menopause Transition and Postmenopausal Hormone Therapy. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York: McGraw-Hill; 2012.
- Musselwhite LW, Sheikh V, Norton TD, et al. Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. AIDS. 2011 Mar 27;25(6):787-95.
- Rasmussen LD, Dybdal M, Gerstoft J, et al. HIV and risk of venous thromboembolism: a Danish nationwide population-based cohort study. HIV Medicine. 2011 Apr;12(4):202-10.
- Ledwaba L, Tavel JA, Khabo P, et al. Pre-ART levels of inflammation and coagulation markers are strong predictors of death in a South African cohort with advanced HIV disease. PLoS One. 2012;7(3):e24243.
- Funderburg NT, Mayne E, Sieg SF, et al. Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation. Blood. 2010 Jan 14;115(2):161-7.
- Pandrea I, Cornell E, Wilson C, et al. Coagulation biomarkers predict disease progression in SIV-infected nonhuman primates. Blood_._ 2012 Aug 16;120(7):1357-66.
- Asztalos BF, Mujawar Z, Morrow MP, et al. Circulating Nef induces dyslipidemia in simian immunodeficiency virus-infected macaques by suppressing cholesterol efflux. Journal of Infectious Diseases. 2010 Aug 15;202(4):614-23. PLoS One. 2012;7(3):e24243.
- Shannon RP, Simon MA, Mathier MA, et al. Dilated cardiomyopathy associated with simian AIDS in nonhuman primates. Circulation. 2000 Jan 18;101(2):185-93.