JANET P. PREGLER, MD; CAROLYN J. CRANDALL, MD, MS. ANNALS OF INTERNAL MEDICINE. 2011; 155:52-

57.

JULIANNA L. MURPHYPHARM.D. CANDIDATE

PRECEPTOR: ALI RAHIMI, MDAUGUST 26, 2011

Update in Women’s Health: Evidence Published in 2010

Issues in Women’s Health

OsteoporosisMenopauseHereditary breast and ovarian cancerCervical cancer and HPV testingEmergency contraception

Osteoporosis: Bisphosphonate Therapy

Generally considered first-line therapy Reduces risk of vertebral, nonvertebral, and hip fractures Good safety profile

Increased rates of subtrochanteric and diaphyseal femur fractures?

3 large randomized trials FIT FLEX HORIZON-PFT

Not associated with higher risk for femur fractures HR for alendronate vs. placebo (FIT) 1.03 (CI: 0.06 to 16.46) Continued alendronate vs. placebo (FLEX) 1.33 (CI: 0.12 to

14.67) Zoledronic acid vs. placebo (HORIZON-PFT) 1.50 (CI: 0.25 to

9.00)

Limitations and Implications

Limitations Wide confidence intervals due to rare occurrence of

femur fractures Secondary analysis only reviewed studies on

alendronate and zoledronic acid Influence of duration of treatment not discernible

Implications Causal relationship not established Risk for atypical fracture does not outweigh benefits

of bisphosphonate therapy Femur fracture should be considered in women

presenting with signs and symptoms, regardless of bisphosphonate therapy status

Calcium and Vitamin D

Calcium and Vitamin D commonly used as dietary supplements

Potential increased cardiovascular riskPossible beneficial effect of vitamin D on

diabetes and hypertension risk

Calcium, Vitamin D, and Cardiovascular Risk

Secondary analysis of 8 randomized trials to assess effect on cardiovascular risk No effect with calcium, vitamin D, or combination

supplementation Possible reduction in CVD mortality with vitamin D

Limitations Few eligible studies available Not designed to assess effect on cardiovascular risk No analysis based on race, gender, or ethnicity

Recommendations about supplementation based on cardiovascular risk are not supported by good evidence

Effects of Vitamin D on Diabetes, Hypertension

Systematic review examining 13 observational studies and 18 randomized trials 3 of 6 analyses based on 4 different cohorts showed

lower risk for diabetes in higher vitamin D groups 8 randomized trials showed no effect of

supplementation on diabetes Meta-analysis of 3 cohorts found lower 25-

hydroxyvitamin D concentrations were associated with hypertension

Not recommended to supplement vitamin D for prevention of diabetes or hypertension

Menopause: Hormonal Therapy

Women’s Health Initiative (WHI) study on conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA)

16,608 women randomly assigned to CEE (0.625 mg/day) plus MPA (2.5 mg/day) therapy or placebo 12,788 of these women consented to follow-up

Risk for invasive cancer was 25% higher in treatment group vs. placebo (HR, 1.78: CI, 1.07 to 1.46)

More deaths attributed to breast cancer in treatment group (HR, 1.57: CI, 1.01 to 2.48)

Women should consider increased cancer risk when weighing risks and benefits of HRT

Menopause: Hormonal Therapy

CEE plus MPA increases risk for CHD in postmenopausal women Limited to women who start therapy late in menopause?

Adherence-adjusted analysis of the WHI data of 16,608 postmenopausal women

Women within 10 years of menopause, HR for CHD events was 1.29: CI, 0.52 to 3.18 for first 2 years after randomization and 0.64: CI, 0.21 to 1.99 for the first 8 years after randomization

Results not statistically significantWomen who begin CEE plus MPA therapy at

menopause should NOT expect a reduction in CHD risk

Menopause: Weight Loss and Hot Flushes

Multiple cohort studies have shown more that women with higher BMI report more hot flushes

Randomized, controlled trial comparing an intensive behavioral weight loss intervention to a structured educational program to promote weight loss

338 overweight or obese women enrolledAt start of study, 154 women reported

bothersome hot flushes

Menopause: Weight Loss and Hot Flushes

Reductions in weight, BMI, and abdominal circumference associated with reduced hot flushes Weight (OR: 1.32, CI: 1.08 to 1.61) per 5-kg decrease BMI (OR: 1.17, CI: 1.05 to 1.30) per 1-kg/m2 decrease Abdominal circumference (OR: 1.32, CI: 1.07 to 1.64)

per 5-cm decreaseMore women lost to follow-up in control

group (educational program) than in the intervention group

Overweight/obese women may reduce hot flushes by losing weight

Hereditary Breast and Ovarian Cancer

BRCA mutations BRCA1 and BRCA2: tumor suppression genes Associated with breast-ovarian cancer syndrome Account for 5 to 10 % of all breast cancer cases in

women Harmless to high-risk variations

Women with harmful mutation have ~5 times the normal risk of breast cancer, ~10 to 30 times the risk for ovarian cancer

BRCA Mutations and Risk-Reducing Surgery

Multicenter, prospective cohort2482 carriers of BRCA1 or BRCA2 mutations Prophylactic mastectomy

247 recipients, 0 breast cancer diagnoses 1372 women without prophylactic mastectomy, 98 breast

cancer diagnoses

Prophylactic salpingo-oophorectomy Recipients had lower all-cause mortality, 10% vs. 3% (HR, 0.44:

CI, 0.26 to 0.61) Recipients had lower ovarian cancer-specific mortality, 3% vs.

0.4% (HR, 0.21: CI, 0.06 to 0.80)

Counseling regarding risks and benefits of surgery should be given to all women with BRCA mutations

Cervical Cancer and HPV Testing

Testing for high-risk HPV DNA in women who have atypical cells is standard practice

U.S. Preventative Services Task Force found insufficient evidence to recommend HPV testing to screen for cervical cancer in 2003

Compared cervical cytology screening with those of high-risk HPV screening with or without cytology screening

Italian women Aged 25 to 60 years

Cervical Cancer and HPV Testing

33,851 women received cervical cytology screening alone

32,998 women received HPV screening followed by a second round of cytology screening alone

9 cases of cervical cancer in the group that had initially had cytology screening alone

0 cases of cervical cancer were found in the second round of screening in the HPV screening group

Among women aged 35 to 60 years Relative detection rate at the first round was 2.08 (CI: 1.47 to 2.95)

for HPV testing vs. cytology screening Relative detection rate at the second round was 0.48 (CI: 0.21 to

1.11)

Emergency Contraception

Levonorgestrel 1.5 mg is the most widely used emergency contraceptive in the United States Not completely efficacious Must be taken soon after intercourse

Ulipristal, a selective progesterone-receptor modulator, seems to be more efficacious in preventing ovulation than levonorgestrel

Emergency Contraception

2,221 women randomly assigned to receive ulipristal (30 mg) or levonorgestrel (1.5 mg)

Follow-up conducted 5 to 7 days after next expected menses

Rates of pregnancy did not significantly differ if treatment was begun within 72 hours of intercourse

203 women received treatment between 72 and 120 hours after intercourse 3 pregnancies occurred in levonorgestrel group 0 pregnancies in ulipristal group

Emergency Contraception

Meta-analysis of this and a previous trial 24 pregnancies in 1617 women randomly assigned to ulipristal 35 pregnancies in 1625 women randomly assigned to

levonorgestrel OR: 0.58, CI:0.33 to 0.99

Limitations Women receiving hormonal contraceptives were excluded Women were advised to abstain from sexual intercourse or to

use barrier methods for remainder of cycle

Ulipristal 30 mg approved by FDA for the prevention of pregnancy up to 120 hours after unprotected sex