Thursday 18 September 2014

Tempted to substitute HRT?


Women with menopausal symptoms may need guidance, given the lure of bioidentical hormones.
Professor Henry Burger
MD, FRACP, FCP(SA), FRCOG, FRANZCOG, FAA
Endocrinologist, Jean Hailes for Women’s Health
THE multibillion-dollar bio­identical hormone industry is rising in popularity, fuelled by highly successful marketing and the initial findings of the 2002 US Women’s Health Initiative (WHI) study.
Wrongly extrapolated findings from the WHI on the use of menopausal HRT resulted in rates of use dropping by up to 80%. Symptomatic women have been driven to seek alternative therapies, including bioidentical hormones, leaving them at risk of harm or of paying a lot of money for no greater effect than placebo.
GPs are well placed to provide evidence-based information to symptomatic women.
Bioidentical hormones are plant-derived products compounded in pharmacies and may be dispensed over the internet. They are marketed as natural, safe, risk-free, age-reversing, sex-enhancing and cancer-preventing.
However, their variable combinations of oestrogens, progesterone, DHEA, testosterone and sometimes thyroxine, melatonin and growth hormone remain untested for long-term safety and efficacy. They are not approved by the TGA or the US Food and Drug Administration.
In a 2008 Australian population sample, 37% of women on hormone therapy aged 50—59 were using unregistered, imported and unaudited bio­identical hormones made into buccal troches or creams. The oestrogens used can cause endometrial proliferation and the progesterone added (if at all) may not inhibit this endometrial stimulus. Four cases of endometrial cancer (including one subsequent death) have followed the use of unregistered HRT in Australia.
In July 2002, the first results of the WHI randomised, controlled trial (RCT) of combined continuous menopausal hormone therapy were announced, emphasising the finding of a 26% increase in breast cancer risk in treated women.
It was not explained that the 26% increase meant less than one additional case of breast cancer per 1000 women taking menopausal HRT above the baseline risk of about three per 1000 per year, and “technically not statistically significant”.
Little attention was paid to the mostly reassuring results of the oestrogen-only arm of the WHI, published in 2004, that showed a “technically not statistically significant” reduction in breast cancer after seven years of oestrogen-alone HRT.
Also ignored was the finding that 76% of the approximately 8000 participants in each arm of the combined trial had never used HRT previously and, in them, no increase in breast cancer risk was seen. Furthermore, the finding that HRT increased the risk of heart disease across the entire age spectrum, 50—79 years, was later found not to be true.
A number of papers re-analysing the WHI study have found the initial findings to be misleading. LaCroix et al (JAMA, 2011) found among postmenopausal women with prior hysterectomy followed up for 10.7 years, conjugated equine oestrogen use for a median of 5.9 years was not associated with an increased or decreased risk of CHD, deep vein thrombosis, stroke, hip fracture, colorectal cancer or total mortality.
A decreased risk of breast cancer persisted and results were more favourable in the 50- to 59-year age group (Manson et al, JAMA, 2013). Few of the outcomes reported in the latter paper are in fact statistically significant and most risks <1 per 1000 per year.
Rossouw et al (JAMA, 2007) found that the health consequences of hormone therapy may vary by time since menopause, with a decrease in CHD risk for women within 10 years of menopause, and particularly high risks in women who are more than 20 years from menopause and have vasomotor symptoms.
No effect on risk of CHD was found and total mortality was reduced among women aged 50—59. The findings are consistent with current recommendations that hormone therapy be used in the short term for relief of moderate or severe vasomotor symptoms, but not in the longer term for prevention of cardiovascular disease.
It is difficult to document loss of health-related quality of life for the generation of women influenced by the highly publicised but misapplied WHI (2002) claims on the risks of HRT.
Short-term RCTs confirm that HRT is the only therapy that effectively improves health-related quality of life in symptomatic women through a reduction in vasomotor and urogenital symptoms, joint pains and insomnia, while improving sexuality.
References
1.Burger H, MacLennan A, Huang K, Castelo-Branco C. Evidence-based assessment of the impact of the WHI on women’s health. Climacteric: The Journal Of The International Menopause Society [serial online]. June 2012;15(3):281-287. Available from: MEDLINE Complete, Ipswich, MA. Accessed April 22, 2014.
2.Eden J, Hacker N, Fortune M. Three cases of endometrial cancer associated with “bioidentical” hormone replacement therapy. The Medical Journal Of Australia [serial online]. August 20, 2007;187(4):244-245. Available from: MEDLINE, Ipswich, MA. Accessed April 22, 2014.
3.LaCroix AZ, Chlebowski RT, Manson JE, et al. Health Outcomes After Stopping Conjugated Equine Estrogens Among Postmenopausal Women With Prior Hysterectomy: A Randomized Controlled Trial. JAMA. 2011;305(13):1305-1314. doi:10.1001/jama.2011.382
4.Rossouw JE, Prentice RL, Manson JE, et al . Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007;297:1465 – 77. Erratum in JAMA 2008;299:1426
5.Manson JE, Chlebowski RT, Stefanick ML et al Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women’s Health Initiative  Randomised Trials JAMA 2013;310, 1353-1368.

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