HIV and Menopause - PowerPoint Presentation

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