What’s new in menopause management? Associate Professor John Eden School of Women’s & Children’s Health Providing Care in Partnership with Women

School of Women’s & Children’s Health Providing Care in Partnership with Women Disclaimer 1.Scientific adviser for –Wyeth, AstraZenica, Lawley Pharmaceuticals 2.My research unit performs trials for the pharma, food & supplement industries

School of Women’s & Children’s Health Providing Care in Partnership with Women Agenda for tonight 1.HT – back again? 2.Genitourinary symptoms 3.Testosterone for women 4.Non-oestrogen drugs for flushes

School of Women’s & Children’s Health Providing Care in Partnership with Women 49y old healthy woman having significant sweats, insomnia and aches and pains. Is it safe for me to take HT?

School of Women’s & Children’s Health Providing Care in Partnership with Women Yes

School of Women’s & Children’s Health Providing Care in Partnership with Women Update of WHI 2002 “Stop HRT & see your doctor” Average age 68Y, >5y combined HT – 8 extra BrCa/ 10,000pa, but 8 fewer other cancers 2004, 2006 CEE alone – reduced risk of intra- ductal BrCa; neutral on lobular

School of Women’s & Children’s Health Providing Care in Partnership with Women WHI 2007 – age specific results “The absence of excess absolute risk of CHD & the suggestion of reduced total mortality in younger women [aged years] offers some reassurance that hormones remain a reasonable option for the short-term treatment of menopausal symptoms, but does not necessarily imply an absence of harm over prolonged periods of hormone use.”

School of Women’s & Children’s Health Providing Care in Partnership with Women MJA June 2008

School of Women’s & Children’s Health Providing Care in Partnership with Women Take-Home message 1.HT is safe for most women <60y 2.Be cautious about starting HT in women >65y with no symptoms! 3.Long-term flushers: patch plus Mirena? 4.HT is not an anti-aging therapy

School of Women’s & Children’s Health Providing Care in Partnership with Women Compounded HT 1.No formal QC 2.No safety studies 3.No efficacy studies 4.No endometrial studies 5.Three cases of endometrial cancer reported (MJA 2007; 187 [4]:244-5)

School of Women’s & Children’s Health Providing Care in Partnership with Women 60y woman with recurrent UTIs and severe dyspareunia

School of Women’s & Children’s Health Providing Care in Partnership with Women Australian survey 1.Only 9% of Australian women recognized vaginal dryness as a treatable menopausal symptom 2.Of those who had the symptom, 77% rated it as moderate or severe. 3.Vaginal dryness increases with age

School of Women’s & Children’s Health Providing Care in Partnership with Women Multicultural Menopause study, Sydney Studied 5 ethnic groups in Sydney 2.Focus groups, (culturally sensitive) 3.Surveys using MENQOL (translated and checked)

School of Women’s & Children’s Health Providing Care in Partnership with Women Vaginal dryness Menopause status Pre-Peri-Post-P value Chinese Thai Lebanese Indian Greek 35% 24% 18% 7% 90% 41% 43% 54% 17% 63% 75% 79% 32% 31% <0.001 <0.01 <0.05 <0.01 <0.05

School of Women’s & Children’s Health Providing Care in Partnership with Women Prevalence of sexual symptoms Decline in sexual desire Avoiding intimacy Chinese Thai Lebanese Indian Greek 48% 76% 69% 38% 45% 44% 46% 54% 32% 40%

School of Women’s & Children’s Health Providing Care in Partnership with Women Genitourinary symptoms 1.The impact of oestrogen lack on the bladder and vagina 2.Safety of topical estrogens –Are they absorbed? 3.Vulval care –Avoid soap –Use moisturizers (Sorbolene, Replens –Olive oil; Sylk

School of Women’s & Children’s Health Providing Care in Partnership with Women Update on sexuality & hormones

School of Women’s & Children’s Health Providing Care in Partnership with Women Oestrogen IncreasedDecreased 1.Sexual activity 2.Enjoyment 3.Desire 4.Arousal 5.Satisfaction 6.Vaginal lubrication 7.Feeling attractive 1.Dyspareunia 2.Vaginal dryness 3.Sexual problems Menopause, 2004; 11:749-65

School of Women’s & Children’s Health Providing Care in Partnership with Women Testosterone update 1.In contrast to oestrogens, androgen levels do not fall precipitously at the time of natural menopause, but rather decline with age particularly after 40 years. 2.Total testosterone levels in women in their 40’s are about 50% lower than that of women in their 20’s. 3.Bilateral salpingo-oophorectomy, in both pre and postmenopausal women results in an immediate 50% reduction in circulating serum testosterone levels.

School of Women’s & Children’s Health Providing Care in Partnership with Women Testosterone update 1.Testosterone cream or patches will increase testosterone levels in women. 2.RCTs show a statistically significant increases in sexual activity – but is it clinically significant. FDA says, “No.”

School of Women’s & Children’s Health Providing Care in Partnership with Women Others 1.Peripheral acting agents –PDE5 inhibitors – don’t work –VIP? –Topical PGE1 agonists? –NO agents? 2.Central acting agents –Apomorphine? –Melanocortin agonists? –5HT1A agonists: Flibanserin, OPC ?

School of Women’s & Children’s Health Providing Care in Partnership with Women Non-hormonal drugs for flushes

Nelson et al. JAMA 2006; 295, 17 : SSRI & SNRI meta-analysis Paroxetine inhibits CYP2D6 & reduces some of tamoxifen’s metabolites

Nelson et al. JAMA 2006; 295, 17 : Clonidine meta-analysis

School of Women’s & Children’s Health Providing Care in Partnership with Women Non-oestrogen drugs 1.Gabapentin 2.Three in phase 3,4 testing –“a derivative of an antidepressant” –“a derivative of gabapentin” –“an antihistamine”

School of Women’s & Children’s Health Providing Care in Partnership with Women Black Cohosh 1.Mixed studies –Mostly positive 2.Most studied extract is Remifemin 3.Formal toxicology studies – safe 4.Breast and uterus studies - safe 5.Used for >50yr in Germany 6.Idiosyncratic hepatic failure – extremely rare

School of Women’s & Children’s Health Providing Care in Partnership with Women Remifemin Osmers, Obstet Gynecol 2005; 105, RCT Remifemin 2/d v. placebo; 12 weeks; n=304 Used Menopause rating scale (MRS) Remifemin more effective than placebo for total MRS (p<0.001) Effective for the hot flush & psychological sub scores No difference for adverse effects

School of Women’s & Children’s Health Providing Care in Partnership with Women Remifemin Plus [StJW] Uebelhack(Obstet & Gynecol 2006; 107, ) RCT Remifemin Plus v. placebo; 16 weeks; n=301 Subjects had significant menopausal symptoms and mild-mod depression Mean MRS decreased 50% in treatment group vs 20% for placebo (p<0.001) Hamilton depression score decreased 42% in treatment group vs 19% for placebo (p<0.001) No difference for adverse effects

School of Women’s & Children’s Health Providing Care in Partnership with Women Rebbeck. Int J Can 2007; 120: Case-controlled study of herbal usage and breast cancer risk 949 breast cancer cases & 1,524 controls Remifemin usage was associated with reduced breast cancer risk, OR 0.47 [CI ] –Consistent with cell culture studies Protective effect not seen for isoflavones, Dong quai or DHEA

School of Women’s & Children’s Health Providing Care in Partnership with Women Case 45y woman who has had a double mastectomy for breast cancer. On Tamoxifen. Problems – severe flushing, chest wall pain, severe vaginal dryness.

Nelson, Lancet 2008

School of Women’s & Children’s Health Providing Care in Partnership with Women 1.Avoid aggravators 2.Paced respiration 3.Increase dietary soy and fibre 4.Remifemin 2-4/d 5.Some soy extracts 6.SSRI or SNRI 7.Clonidine 8.Gabapentin “I don’t want to take HT”