Menopause plaats van alternatieven Serge Rozenberg UMC St

Menopause : plaats van alternatieven? Serge Rozenberg UMC St Pieters serge_rozenberg@stpierre-bru. be serge. rozenberg@skynet. be President of EMAS Lentevergadering VVOG 06. 03. 10 Conflicts of interest: none

Pubmed: Menopause and alternative treatment : 897 hits • Clinical trial or RCT or meta-analyses (English): 207 • Meta-analyses : 5 • Excluding Osteoporosis (biphosphonates, SERMS, …)

Symptom severity was also significantly reduced compared with placebo OR= 0. 13, 95% CI 0. 08 -0. 22. Mac. Lennan et al Climacteric. 2001 Mar; 4(1): 58 -74. /Cochrane review

Nonhormonal Therapies for Menopausal Hot Flushes: Systematic Review and Meta. Analysis • (1966– 2005) 4, 249 abstracts -> 43 trials met inclusion criteria, including 10 trials of antidepressants, 10 trials of clonidine, 6 trials of other prescribed medications, and 17 trials of isoflavone extracts. • Nelson et al. JAMA 2006; 295: 2057– 71.

Nonhormonal Therapies for Menopausal Hot Flushes: Systematic Review and Meta. Analysis • The number of daily hot flushes decreased compared with placebo in meta-analyses of 7 comparisons of selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) • mean difference – 1. 13 (95% CI– 1. 70 to – 0. 57) • Nelson et al. JAMA 2006; 295: 2057– 71.

Paroxetine controlled release in the treatment of menopausal hot flashes: randomized controlled trial. Stearns V, et al JAMA 2003; 289: 2827– 34

Nonhormonal Therapies for Menopausal Hot Flushes: Systematic Review and Meta. Analysis • The number of daily hot flushes decreased compared with placebo in meta-analyses of 4 trials of clonidine • – 0. 95, (95% CI – 1. 44 to – 0. 47), • Nelson et al. JAMA 2006; 295: 2057– 71.

Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifeninduced hot flashes: • Double-blind, placebo-controlled : 194 using tamoxifen • Oral clonidine hydrochloride, 0. 1 mg/d/ placebo for 8 weeks. • Hot flash : -37% clonidine group -20% placebo group • Clonidine more difficulty sleeping (41% vs 21%; P = 0. 02). • quality-of-life scores (+0. 3 points: clonidine vs 0. 2 points placebo; P = 0. 02) at 8 weeks, although the median difference was 0 in both groups. • Pandya et al Ann Intern Med. May 2000

Nonhormonal Therapies for Menopausal Hot Flushes: Systematic Review and Meta. Analysis • The number of daily hot flushes decreased compared with placebo in meta-analyses of 2 trials of gabapentin • – 2. 05, 95% (CI – 2. 80 to – 1. 30). • Nelson et al. JAMA 2006; 295: 2057– 71.

Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial Pandya Lancet 2005

Nonhormonal Therapies for Menopausal Hot Flushes: Systematic Review and Meta. Analysis • Frequency was not reduced in metaanalysis of trials of red clover isoflavone extracts, and results were mixed for soy isoflavone extracts. • Evidence of the efficacy of otherapies is limited due to the small number of trials and their deficiencies. • Nelson et al. JAMA 2006; 295: 2057– 71.

• • • Nonhormonal Therapies for Menopausal Hot Flushes: Systematic Review and Meta. Analysis No head to head comparison: relative efficacy cannot be determined. SSRIs or SNRIs, clonidine, and gabapentin: evidence but effects are less than for estrogen, generalizability is limited, and adverse effects and cost may restrict use for many women. These therapies may be most useful for highly symptomatic women who cannot take estrogen but are not optimal choices for most women. Nelson et al. JAMA 2006; 295: 2057– 71.

Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. • Trifolium pratense (red clover) isoflavones • RCT of monopreparations containing T. pratense isoflavones for treating hot flushes. • 17 potentially relevant articles-> 5 were suitable • Coon et al Phytomedicine. 2007 Feb; 14(2 -3): 1539. Epub 2007 Jan 18.

Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. • Reduction in flush frequency in the active group (40 -82 mg daily) vs placebo. • weighted mean difference -1. 5 hot flushes/daily; (95% CI -2. 94 to 0. 03; p=0. 05). • Coon et al Phytomedicine. 2007 Feb; 14(23): 153 -9. Epub 2007 Jan 18.

Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. • There is evidence of a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women. • Whether the size of this effect can be considered clinically relevant is unclear. • No apparent evidence of adverse events during short-term use, there are no available data on the safety of long-term administration. • Coon et al Phytomedicine. 2007 Feb; 14(2 -3): 153 -9. Epub 2007 Jan 18.

Phytoestrogens for vasomotor menopausal symptoms • RCT at least 12 weeks and where the intervention was a food or supplement with high levels of phytoestrogens (and not combined with other herbal treatments). • Excluded: breast cancer • Studies were grouped into broad categories: dietary soy, soy extracts, red clover extracts and other types of phytoestrogen. • 5 trials used Promensil, a red clover extract; were combined. • Anne Lethaby et al , Cochrane group (Review 2007 no change to conclusions 2009).

Phytoestrogens for vasomotor menopausal symptoms • 30 trials comparing phytoestrogens with control • Of the five trials with data suitable for pooling: no significant difference overall in the frequency of hot flushes between Promensil (a red clover extract) and placebo (WMD=-0. 6, 95% CI -1. 8 to 0. 6). • There was no evidence of a difference in percentage reduction in hot flushes in two trials between Promensil and placebo (WMD=20. 2, 95% CI -12. 1 to 52. 4). • Anne Lethaby et al , Cochrane group (Review 2007 no change to conclusions 2009).

Phytoestrogens for vasomotor menopausal symptoms • Remaining trials: Some of the trials found that phytoestrogen treatments alleviated the frequency and severity of hot flushes and night sweats when compared to placebo but many of the trials were of low quality and were underpowered. • There was a strong placebo effect in most trials with a reduction in frequency ranging from 1% to 59% with placebo. • Anne Lethaby et al , Cochrane group (Review 2007 no change to conclusions 2009).

Phytoestrogens for vasomotor menopausal symptoms • No indication that the discrepant results were due to the amount of isoflavone in the active treatment arm, the severity of vasomotor symptoms or trial quality factors. • There was also no evidence that the treatments caused oestrogenic stimulation of the endometrium (an adverse effect) when used for up to two years. • Anne Lethaby et al , Cochrane group (Review 2007 no change to conclusions 2009).

Phytoestrogens for vasomotor menopausal symptoms • “There is no evidence of effectiveness in the alleviation of menopausal symptoms with the use of phytoestrogen treatments. ” • Anne Lethaby et al , Cochrane group (Review 2007 no change to conclusions 2009).

A SURVEY AMONG BREAST CANCER SURVIVORS: TREATMENT OF THE CLIMACTERIUM AFTER BREAST CANCER • 206 valid responses (64% response rate) • QOL (Women Health Questionnaire) • Flushes: > 60% of postmenopausal women. (Half severe) • 1/3 used various products to alleviate postmenopausal symptoms • Younger women 3 X more frequently but they did not use treatment more often. • Antoine et al Climacteric 2009

Systematic review & meta-analysis: Gabapentin for hot flashes in women with natural or tamoxifen-induced menopause: Toulis et al Clin Ther. 2009

Stellate-ganglion block on recorded hot Flushes, night Awakenings, severity of hot flushe over 12 -week follow-up period Lipov et al Lancet Oncol. 2008

General recommendations • Achieve a normal wheight, • Identify triggers to their hot flashes (eg, alcohol, hot drinks, or spicy food) ? • Relaxation ?

A randomized controlled trial of relaxation training to reduce hot flashes in women with primary breast cancer. Change in number of flashes (median and interquartile range)/week after 1 month • Fenlon et al J Pain Symptom Manage. 2008

Caution: Vaginal estradiol appears to be contraindicated in postmenopausal women on adjuvant aromatase inhibitors Kendall et al Annals of Oncology 17: 584– 587, 2006

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