NORTHWEST AIDS EDUCATION AND TRAINING CENTER

This presentation is intended for educational use only, and does not in any way constitute medical consultation or advice related to any specific patient.

HIV and Menopause

Ruanne Barnabas, MBChB, DPhilAssistant ProfessorDepartments of Global Health, Medicine and Epidemiology

Date: 9/3/15

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 events• Non-AIDS-defining

infections• Renal disease• Non-AIDS-defining

cancers/malignancy• Muscular and skeletal

changes• Non-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 Johnson

Menopause

• ≥12 consecutive months - amenorrhea (not surgery or another obvious cause)

• Age at which natural menopause - marker of aging

• Later 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, atherosclerosis

- Preserved bone density and reduced risk of osteoporosis and fracture

- Increased risk of breast, endometrial, and ovarian cancers

Santoro N, et.al; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 417–423

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

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10%

15%

20%

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30%

HIV infected HIV uninfected% o

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Figure adapted from Margaret Johnson

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

Smoking Socioeconomic 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 Johnson

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:

- Cardiovascular disease (CVD)

- Diabetes

- Osteopenia / osteoporosis

• Early onset menopause (before 46 years):

- Increases the risk of these diseases

- May 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):1044-1049

Evaluation of Reproductive Aging and Predictors of Ovarian Function

• Follicle Stimulating Hormone (FSH)- Sustained rise in late menopausal transition, and precipitous around the

final menstrual period- Early 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 life- Earliest and most effective way to measure a woman’s progress toward

menopause

• No difference between HIV+ and HIV-negative women

Santoro N; Obstet Gynecol Clin North Am. 2011 Sep; 38(3): 425-440

Estrogen has significant cardiovascular effects, which include:

A. Vasodilatation

B. Prevention of smooth muscle cell proliferation

C. Inhibition of LDL deposition in the vascular wall

D. Inhibition of platelet aggregation and stress-induced endothelial injury

E. All of the above

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 artery

• Vaginal dryness

• Sleep disturbances

• Mood disorders

• Decrease QOL

Chae CU, et.al; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 477-488

Recommendations for evaluation of bone disease in HIV

A. Screening for osteoporosis all men >50 with Bone densitometry (DEXA Scan).

B. Screening with DEXA scan all HIV infected postmenopausal women.

C. Screening with DEXA all HIV infected who have a history of fragility fracture.

D. Screening with DEXA all receiving chronic glucocorticoid treatment or at high risk of falls

E. All of the above

Brown, T and colleagues, Bone disease in HIV, CID, 2015

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.

Managing the menopause in women with HIV

• Strategies to offset effects associated with menopause include:- Healthy lifestyle choices

- Smoking cessation

- Adherence to effective ART

- HRT – limited data

- Anti-inflammatories - statins

- Symptom management

- Mood/mental health

- Alternative therapies

Kanapathipillai, Menopause, 2013

Algorithm for management of menopause

Kanapathipillai, Menopause, 2013

Management of menopausal symptoms (1)

• Exclude other causes:- Non HIV related: depression, thyroid, drug side effects, - HIV related: OI, malignancy including lymphoma

• Lifestyle choices: Smoking cessation and ART adherence

• Alternatives 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) – venlafaxine- Gabapentin (consistent effect and no interactions with ART)- Clonidine

Chae CU, et.al; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 477-488

Drug Interactions by ART class

McPheeters, C, JNP, 2013

Management of menopausal symptoms (2)

• Complementary therapies, including omega-3 fatty acids, and soy-derived isoflaones, decrease symptoms

• Black cohosh (Cimicifuga racemosa) – serious liver reactions reported

• Topical oestrogen creams or lubricants - Local administration of oestrogen is not associated with the same risks as systemic HRT

• Acupuncture

• Yoga

Chae CU, et.al; Obstet Gynecol Clin North Am. 2011 Sept; 38(3): 477-488

Treatment options for HIV+ women

McPheeters, C, JNP, 2013

Hormone replacement therapy in women living with HIV

• HRT – SOC until associated with breast ca., stroke, CAD and PE

• Lowest effective dose and shortest possible time – symptoms recur in 50%

• HRT – no guidance for use among HIV+ women

• Risks may outweigh the benefits if they:

- Smoke

- Are overweight

- Have 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, 2013

Discussion

• Uncomplicated HIV+ woman, treatment options for HIV uninfected women may be worthwhile

• Check drug interactions

• Need for research to address this gap in evidence for clinical practice

• Given increasing life-expectancy of HIV+ women, this is a priority for research