Ruanne Barnabas MBChB DPhil Assistant Professor Departments of Global Health Medicine and Epidemiology Date 9315 Women living with HIV face all the challenges that the general population faces when growing older ID: 549314
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Slide1
HIV and Menopause
Ruanne Barnabas, MBChB, DPhilAssistant ProfessorDepartments of Global Health, Medicine and Epidemiology
Date: 9/3/15Slide2
Women living with HIV face all the challenges that the general population faces when growing older
PLUS:Consequences of aging as a woman with HIV
Conditions with increased incidence in women living with HIV:
Hormonal
changes
Cardiovascular eventsNon-AIDS-defining infectionsRenal diseaseNon-AIDS-defining cancers/malignancyMuscular and skeletal changesNon-AIDS-dementias, neurocognitive changes, mood and CNS disorders
The consequences of living longer with HIV
The consequences of longer exposure to HIV treatment regimens
Figure adapted from Margaret JohnsonSlide3
Menopause
≥12 consecutive months - amenorrhea (not surgery or another obvious cause)Age at which natural menopause - marker of agingLater age at menopause associated with:
Longer overall survival and greater life expectancy
Reduced all-cause mortality
Reduced risk of
CV disease,
stroke, angina after MI, atherosclerosisPreserved bone density and reduced risk of osteoporosis and fractureIncreased risk of breast, endometrial, and ovarian cancersSantoro N, et.al; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 417–423Slide4
Menopause among HIV+ women
Women living with HIV were 73% more likely to experience early onset of menopause compared with HIV-uninfected women (P=0.024)Schoenbaum et al (2005) Clin Infect Dis
Figure adapted from Margaret JohnsonSlide5
5
Thompson SC et al.
AIDS Care
1996;8(1):5-
14; Willett
W et al.
Am J Epidemiol 1983;117:651-658; Cooper GS et al. Epidemiology 1999;10:771-773; Luoto R et al. Am J Epidemiol 1994;139(1):64-76; http://www.cdc.gov/hiv/topics/women/resources/factsheets/pdf/women.pdf
Potential contributors to early onset of menopause in women with HIV
SmokingSocioeconomic status
Menopause can occur up to 1–2 years earlier in smokers, compared with non-smokers
Markers of low socioeconomic status (e.g. lower level of education, unemployment and poverty) have been associated with early menopause onset
Lower CD4+ count has been associated with early menopause onset
Immunosuppression
Inconsistent
factors: Race, ethnicity, BMI or body composition, physical activity, diet
Figure adapted from Margaret JohnsonSlide6
6
Menopause: Associated changes in health risks
The menopause - marked by the ending of menstruation and ovulation
Falling levels of estrogen
Onset of the menopause is associated with an increased risk of:
C
ardiovascular disease (CVD)Diabetes Osteopenia / osteoporosisEarly onset menopause (before 46 years):Increases the risk of these diseasesMay be linked to increased mortalitySantoro N et al. Maturitas 2009;64:160-164; Carr MC. J Clin Endocrinol
Metab 2003;88:2404-2411; Isaia
GC et al. Exp Gerontol 1990;25(3-4):303-307; Kritz-Silverstein D et al. Am J Public Health 1993;83:983-988; Lisabeth LD et al. Stroke 2009;40(4):1044-1049Slide7
Evaluation of Reproductive Aging and
Predictors of Ovarian FunctionFollicle Stimulating Hormone (FSH)Sustained rise in late menopausal transition, and precipitous around the final menstrual periodEarly follicular phase between cycle days 2 and 5 (more sensitive)Estradiol (E2)Early follicular levels are the last biomarker of the transition to change with rapid decline 2 years prior to menopause
Inhibin
B
Early predictor of menopausal transition
Anti-Mullerian Hormone(AMH)/
Mullerian Inhibitin Substance (MIS)Concentrations decline through reproductive lifeEarliest and most effective way to measure a woman’s progress toward menopauseNo difference between HIV+ and HIV-negative womenSantoro N; Obstet Gynecol Clin North Am. 2011 Sep; 38(3): 425-440 Slide8
Estrogen has significant cardiovascular effects, which include:
VasodilatationPrevention of smooth muscle cell proliferationInhibition of LDL deposition in the vascular wallInhibition of platelet aggregation and stress-induced endothelial injuryAll of the aboveSlide9
Menopause Symptoms
Hot flashes are associated with endothelial dysfunction Decreased flow-mediated dilation Higher levels of aortic calcification and intima media thickness of the common carotid arteryVaginal drynessSleep disturbancesMood disorders
Decrease QOL
Chae
CU,
et.al
; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 477-488Slide10
Recommendations for evaluation of bone disease in HIV
Screening for osteoporosis all men >50 with Bone densitometry (DEXA Scan).Screening with DEXA scan all HIV infected postmenopausal women.Screening with DEXA all HIV infected who have a history of fragility fracture.Screening with DEXA all receiving chronic glucocorticoid treatment or at high risk of fallsAll of the above
Brown, T and colleagues, Bone disease in HIV, CID,
2015Slide11
Finkelstein J,
et.al; J Clin Endocrinol Metab. 2008 March; 93(3): 861–868 Bone and Menopause
Bone loss accelerates substantially in late peri-menopause and the initial postmenopausal years. Body weight is a major determinant.Slide12
Managing the menopause in women with HIV
Strategies to offset effects associated with menopause include:Healthy lifestyle choices Smoking cessationAdherence to effective ART HRT – limited dataAnti-inflammatories - statinsSymptom management
Mood/mental health
Alternative therapies
Kanapathipillai
, Menopause, 2013Slide13
Algorithm for management of menopause
Kanapathipillai, Menopause, 2013Slide14
Management of menopausal symptoms (1)
Exclude other causes:Non HIV related: depression, thyroid, drug side effects, HIV related: OI, malignancy including lymphomaLifestyle choices: Smoking cessation and ART adherenceAlternatives for hot flushes among HIV+ women include:Selective serotonin reuptake inhibitor (SSRI) – paroxetine (inconsistent effect and can inhibit cytochrome P450)Serotonin-norepinephrine reuptake inhibitor (SNRI) – venlafaxineGabapentin (consistent effect and no interactions with ART)ClonidineChae CU,
et.al
;
Obstet
Gynecol
Clin North Am. 2011 Sept; 38(3): 477-488Slide15
Drug Interactions by ART class
McPheeters
, C, JNP, 2013Slide16
Management of menopausal symptoms (2)
Complementary therapies, including omega-3 fatty acids, and soy-derived isoflaones, decrease symptomsBlack cohosh (Cimicifuga racemosa) – serious liver reactions reportedTopical oestrogen creams or lubricants - Local administration of oestrogen is not associated with the same risks as systemic HRTAcupunctureYogaChae CU,
et.al
;
Obstet
Gynecol
Clin North Am. 2011 Sept; 38(3): 477-488Slide17
Treatment options for HIV+ women
McPheeters
, C, JNP, 2013Slide18
Hormone replacement therapy
in women living with HIVHRT – SOC until associated with breast ca., stroke, CAD and PELowest effective dose and shortest possible time – symptoms recur in 50%HRT – no guidance for use among HIV+ womenRisks may outweigh the benefits if they: Smoke
A
re overweight
H
ave had blood clots, breast cancer, diabetes, high cholesterol levels, liver problems, or a family history of heart disease
Estrogen and/or progesterone have interactions with ART (estrogen interacts with PIs and NNRTIs; NRTIs, integrase inhibitors and entry inhibitors have no known significant interactions)Kanapathipillai, Menopause, 2013Slide19
Discussion
Uncomplicated HIV+ woman, treatment options for HIV uninfected women may be worthwhileCheck drug interactionsNeed for research to address this gap in evidence for clinical practiceGiven increasing life-expectancy of HIV+ women, this is a priority for research