DINE AND LEARN ENDOCRINOLOGY PEARLS. Dr. Priya Manjoo, MD, FRCPC Endocrinology, Victoria, BC

Transcription

1 DINE AND LEARN ENDOCRINOLOGY PEARLS Dr. Priya Manjoo, MD, FRCPC Endocrinology, Victoria, BC

2 OUTLINE HRT and CVD HRT and Breast Cancer Osteoporosis When to treat How long to treat for Bisphosphonates BMD frequency of testing

3 Hormone Replacement Therapy Womens Health Initiative: E+ P Trial HR for CHD: 1.24 ( ) Borderline significance Among women <10 years from menopause HR for CHD was 0.76 ( ) Trend for worsening with time since menopause for the other groups

4 HRT: WHI E only 10 year follow up year old women had significantly reduced risk of MI 0.54 ( ) CHD 0.59 ( ) Total mortality (0.73 ( ) Int J Fertil Womens Med. 2002;47:61-68(7)

5 Timing Hypothesis Younger symptomatic women at onset of menopause may be protected form CHD Older women treated for the first time have no benefit and may have early harm

6 Progression of atherosclerosis by age in postmenopausal women Int J Fertil Womens Med. 2002;47:61-68(7)

7 KRONOS Early Estrogen prevention study (KEEP) Surrogate markers evaluated among young women on HRT at onset of menopause. RCT in women within 3 years of menopause Placebo VEE or transdermal estrogen Uterus =micronized progesterone for 12 days each month CIMT increase similar in all groups Non-significant trend for Coronary Calcium score to progess less in the 2 estrogen groups compared with placebo. (Low coronary calcium score at entry)

8 Danish Osteoporosis Study RCT of 1006 younger women at the onset of menopause Open-label fashion with oral estradiol and norethindrone acetate or estradiol alone for 10 years 16 year follow up. Combined endpoint of mortality and hospitalization for heart failure or MI significantly was reduced in those women randomized to HRT compared to the control women randomized to no treatment. Younger the women were in trial the greater the benefit with no increase in thrombosis, stroke or cancer. Schierbeck et al. BMJ 345:e6409 (30)

9 Consensus from Endocrine Society Based on Grade B level Evidence Basic science. Animal models and observational studies support the hypothesis that MHT may prevent atherosclerosis and reduce CHD events Subgroups analysis suggested that the lack of benefit or increase in CHD risk observed in the overall analysis of WHI results from harmful effects of MHD in order women starting therapy many years after the onset of menopause

10 Consensus from Endocrine Society GRADE A Evidence MHD increases the risk of venothrombotic episodes approximately twofold and is multiplicative within baseline risk factors including age higher BMI, thrombophilias, surgery, immobilization

11 Breast Cancer Potential risk of breast cancer into perspective is extremely important in discussing HT with women Estrogen alone may decrease the risk Probably does not increase the risk unless large doses are used for prolonged time in susceptible women with unknown occult tumors E+P in young women initializing standard dose therapy for the first time at the onset of menopause do not appear to have an increased risk of breast cancer for at least 5 years and probably for up to 7 years. But the risk dose increase thereafter (using regime studied in WHI)

12 Breast Cancer But the risk does increase thereafter (using regime studied in WHI) Observational data from France (1) suggest that the risk is not increased with micronized progesterone dihydrogesterone and in DOPS using estradiol and norethindrone there was no increase in breast cancer for up to 11 years and a 16 year follow up. (small trial). Gail Model can be used to estimate cancer risk 1. Fournier et al. Breast Cancer Res Treat. 2008;107;

13 Osteoporosis Dr. Priya Manjoo

14 OUTLINE Osteoporosis Risk Assessment Duration of Bisphosphonate Therapy Failure of Bisphosphonate Therapy Monitoring Therapy

15 OSTEOPOROSIS: ASSESSING RISK Case finding strategy: Fractures present Bone Density (Screening Strategy) WHO classification * Normal: T >-1.0 Osteopenia: T -2.5 to -1.0 Osteoporosis: T -2.5 Clinical Assessment Risk Factors (FRAX Score) Incorporates BMD and risk factors * Postmenopausal women and men >50

16 OSTEOPOROSIS: WHEN TO TREAT Assess Risk Factors and BMD if suitable Hip or vertebral fracture or BMD T-score <2.5 (spine, FN or total hip T-score between -2.5 and -1.0 FRAX Score 10 year probability of hip fracture >3% or major osteoporotic fracture >20% Treat

17 FRAX TOOL

18 FRAX PROBABILITIES BY COUNTRY Baims et al. 2012

19 CHANGES IN BONE MASS

20 BISPHOSPHONATES Duration of therapy Not an issue with diabetes or hypertension medications But it is for osteoporosis Longer duration in bone Longer retention of bone with recycling of drug leaving a reservoir within bone

21 BISPHOSPHONATES Few data available for assessing the efficacy of long- term bisphosphonate use (>5 years) in reducing the risk of fractures. Two randomized trials with a combined sample size of 2342 women FLEX Trial (Aledronate vs Placebo) HORIZON-extension trial (ZA)

22 BISPHOSPHONATES FLEX STUDY Fracture Intervention Trial Long-Term Extension (FLEX), 1099 postmenopausal women who had received aledronate for 5 years Randomized to treatment for another 5 years versus placebo

23 BISPHOSPHONATES Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Extension trial ~1200 Postmenopausal women who had received 3 years of treatment were randomized to another 3 years of placebo or active extension

24 FLEX

25 HORIZON - Extension

26 COMBINED DATA

27 HORIZON - Extension Bone loss after discontinuation of therapy was only modest as compared with that during continued drug therapy suggesting persistance of bisphosphonate effects Patients likely to benefit from extended therapy: low BMD at femoral neck (T <-2.5) after 3-5 years of treatment Existing vertebral fracture and T score <-2.0 may also benefit Femoral neck of above -2.0 have low risk of fracture are unlikely to benefit form continued treatment.

28 PROGRESSION TO OSTEOPOROSIS

29 PROGRESSION TO OSTEOPOROSIS Screening interval of 15 years 10% of older, postmenopausal women with normal bone density or mild osteopenia (T score, > 1.5) at the initial assessment would progress to osteoporosis Screening interval of 5 years 10% of women with moderate osteopenia (T score, 1.50 to 1.99) would progress to osteoporosis Screening interval of 1 year 10% of women with advanced osteopenia T score, 2.00 to 2.49) would progress to osteoporosis