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In People Living with HIV (PLWH), Menopause (natural or surgical) Contributes to the Greater Symptom Burden in Women: results from an online US survey
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Menopause 2019
https://europepmc.org/articles/PMC6014890;jsessionid=A5915FCFDB6907CFBB231188708B7CE4
Rebecca Schnall, PhD, MPH, RN, Haomiao Jia, PhD, Susan Olender, MD, Melissa Gradilla, MPH, and Nancy Reame, PhD, MSN
Rebecca Schnall, Columbia University School of Nursing, 560 West 168thStreet, New York, NY, 10032, USA;
This paper reports on findings from a sex-based analysis of an online survey of PLWH enriched with follow-up data on menopause status in the female subsample. We demonstrated that two of the most common symptoms in PLWH – fatigue and muscle aches/pains - invoke additional burden in women compared to men, independent of aging-related co-morbidities or other clinical factors. The higher symptom burden observed in those reporting natural or surgical menopause suggests that symptom burden may be further exacerbated once menses ceases.
we confirmed a more adverse picture of contemporary HIV infection in females vs. males including a greater burden (frequency and bother) imposed by the most commonly reported HIV symptoms: fatigue, muscle aches/joint pains, depression and poor sleep
the hypoestrogenism induced by menopause has been indicted as the cause of magnified morbidity in women due to effects on the cardiovascular, skeletal, and immune systems.49,50 Despite this, most attention has focused on the impact of HIV on the menopause experience rather than the converse
Discussion
Improvements in survival have led to increasing numbers of WLWH reaching menopause age and beyond,36 but how this accounts for the higher HIV morbidity and worse quality of life observed in women is not clear.36,37 In this study, we sought to better characterize the role of female sex in the contemporary HIV symptom experience using a sample of male and female respondents to a national online survey, supplemented with a follow-up menstrual bleeding questionnaire to infer menopause status. With this approach, we confirmed a more adverse picture of contemporary HIV infection in females vs. males including a greater burden (frequency and bother) imposed by the most commonly reported HIV symptoms: fatigue, muscle aches/joint pains, depression and poor sleep38–40. Our results support earlier sex-based analyses of data obtained from face-to-face interviews where mean burden scores were higher (worse) in women vs. men for both fatigue and muscle aches/joint pain.30,41,42 The consequences of this health disparity is not trivial: individually and in tandem, this adverse symptom profile in women has been associated with a worse quality of life,30,40,43,44 higher global burden,30 more adverse frailty,45 and higher rates of neurocognitive impairment.46
The magnified profile of the symptom experience in women living with HIV (WLHIV) has previously been attributed to sex-based nuances in symptom appraisal and assessment, potential biases in self-reporting,47,48 higher rates of poverty and low education19 as well as biological differences in the disease process itself.30 However, as the proportion of women expands within the aging cohort of affected individuals, the extent to which sex-based differences in HIV symptomatology can be explained by menopause has become of increasing interest. Specifically, the hypoestrogenism induced by menopause has been indicted as the cause of magnified morbidity in women due to effects on the cardiovascular, skeletal, and immune systems.49,50 Despite this, most attention has focused on the impact of HIV on the menopause experience rather than the converse.36,51 For example, in contrast to a rich body of work on menopause features (age of the final menstrual period; menopause symptoms) in WLHIV, the authors of several reviews note the scarcity of attention to menopause effects on HIV outcomes, including quality of life with negligible findings to date.51,52
To overcome one limitation in prior sex-based HIV symptom research, we enriched our female survey with follow-up questions about menstrual bleeding patterns. By dichotomizing the female sample on this variable and accounting for other relevant characteristics, we were able to demonstrate that inferred menopause (natural or surgical) was an independent predictor of distress for the same HIV symptoms as those with markedly worse female burden in our sex-based analysis. The higher burden incurred for fatigue, muscle aches/joint pain and impaired sleep in the post-menopause women after adjusting for age, comorbid conditions and HIV duration is especially troubling given the already increased risk for accelerated bone loss, sarcopenia and frailty in this population.53
To what extent this finding is confounded by an overlap between symptoms of menopause and consequences of HIV is difficult to untangle as this interaction is likely multidimensional and bidirectional, i.e. menopause exacerbates HIV and HIV exacerbates menopause.54 For example, the muscle aches/pains, fatigue and sleep problems attributed here to HIV, are not only common features of menopause in healthy ethnically-diverse populations,22,23,55,56 but when studied as menopause symptoms in WLWH, have demonstrated greater prevalence and severity vs. uninfected peers in most30,57,58 but not all investigations.59 Whether this magnified symptomatology is due to the earlier debut of ovarian aging as measured by lower antimullerian hormone levels in WLWH compared to uninfected counterparts60 awaits a more comprehensive assessment.
With the exception of a well-established link between HIV and hot flash severity,57 consistent evidence for an influence of HIV on menopause-related changes in depressed mood and sleep symptoms is lacking when the most rigorous designs are used. The Women’s Interagency HIV Study (WIHS), a large, US multicenter study of HIV-infected and non–HIV-infected women of similar socioeconomic status, found that despite higher rates of depressed mood in the early perimenopause in both groups (when studied as a menopause symptom), it was not related to HIV status.61 In a second evaluation of the same cohort, only verbal memory as part of a subset of cognitive symptoms was greater in seropositive women; sleep symptoms worsened with more advanced menopause stage but were not predicted by HIV status.33 In our study, we did not see an additive effect of menopause status on symptom burden for depression, although burden scores were second only to those for muscle aches/joint pains. Taken together, these data strengthen the view that depression is a complex and pervasive health problem in WLWH which may not be significantly worsened by menopause.
Such inconsistent findings have led the authors of recent reviews to conclude that factors such as unhealthy lifestyle, economic adversity, accelerated aging, disease mechanisms, and cART pharmacokinetics have been proposed as likely contributors to the magnified symptoms in midlife WLHIV,52 but in a symptom-dependent fashion and with variable interplay across study populations.36,51 Moreover, symptoms such as depressed mood,62,63 fatigue,64 pain39 and impaired sleep65 are known to co-vary for both HIV manifestations as well as menopause,66 demonstrating moderating and mediating effects on one another. To what extent this was a factor here requires further study with both HIV-infected and uninfected peers to examine symptom cluster patterns using biobehavioral measures of menopause status, HIV characteristics and changes over time.
To reduce confusion regarding symptom attribution, we intentionally avoided asking questions about menopause symptoms in either survey. Moreover in our sample, the burden score was low for the item “fever/night sweats/chills” compared to other symptoms and not different between women and men, or elevated in the amenorrheic subsample, suggesting that the female respondents did not confuse HIV manifestations with the night sweats or hot flashes of menopause.
At the same time, both women living with HIV as well as their clinicians may be confused as to the source of symptoms. One study of menopause symptom attribution demonstrated a 3-fold higher number of women with HIV who did not know why they had hot flashes or vaginal dryness vs. the uninfected group.54 In an investigation in WLWH in methadone treatment fewer than 10% of the sample positively identified muscle achiness and poor sleep as menopause symptoms.67 While several researchers have acknowledged the need for greater recognition by clinicians of muscle aches and pains and sleep-related problems as hallmark features of menopause,68,69 for HIV care providers this may be especially true. Taken together, our findings support the inclusion of measures of menopause status in both clinical practice as well as research to better account for the differential symptom burden between men and women living with HIV.
Limitations
There are several limitations to our study. The generalizability of the results is limited to US populations of HIV-infected individuals who are Internet users. Our follow-up survey had a modest response rate and nonresponse bias is possible. At the same time, the use of an online recruitment strategy and survey method may have contributed substantially to the efficient and cost-effective approach for engaging a large research sample where the use of social media is widespread. Additionally, the lack of compensation for respondents may have helped to reduce the potential for fraudulent responses, a special concern in online data collection. We also recognize the selection bias in comparing a largely gay male subsample who was mostly white (70%) with a largely Black, heterosexual female subsamples of lower income and education. Nonetheless, the demographics of our respondents correspond with those typical of the HIV population in the US where African American women with similar backgrounds are disproportionately affected by HIV (61% of diagnoses in 2015) compared to White and Hispanic/Latino women (19% and 15%, respectively).19 As this was a secondary analysis of an existing web-based data set, we were also constrained by the cross-sectional nature of the design limiting our ability to assess causality, the threat of recall bias in responses, and the lack of medical records and clinical biomarkers to confirm HIV characteristics and menopause status. Moreover, it is possible that in some women, especially those in the younger age ranges, the prolonged amenorrhea reported as spontaneous menopause was due to HIV morbidity. Additionally a comparison group of demographically-similar women without HIV would have reduced the risk of inadequate control for other confounding factors likely to explain the association between menopause and symptom burden. Because the SSC-HIVrev survey 26 asks questions pertaining to symptoms associated with HIV infection, and does not ask questions specific to menopausal symptoms, direct causality (menopause status) cannot be established. Finally, gender role was not assessed as a potential contributor to sex-based symptom profiles. Recently, Norris et al70 demonstrated that the difference in angina scores between male and female cardiac patients was attenuated with the inclusion of a gender index tool to differentiate psychosocial factors from biologic sex. Such an approach may be especially valuable in studies of PLWH.
Conclusion
Although women in the US comprise less than one fifth of those with an HIV diagnoses and have a similar life expectancy as men living with HIV, they experience greater symptom burden. This paper reports on findings from a sex-based analysis of an online survey of PLWH enriched with follow-up data on menopause status in the female subsample. We demonstrated that two of the most common symptoms in PLWH – fatigue and muscle aches/pains - invoke additional burden in women compared to men, independent of aging-related co-morbidities or other clinical factors. The higher symptom burden observed in those reporting natural or surgical menopause suggests that symptom burden may be further exacerbated once menses ceases. As the number of women transitioning through menopause expands within the aging HIV cohort, the needs of this population are likely to require a multidisciplinary team of health care experts and new directions for HIV care management.
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