What’s new in menopause management? Associate Professor John Eden School of Women’s &...

What’s new in What’s new in menopause menopause management?management?

Associate Professor John Eden

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


DisclaimerDisclaimer

1.Scientific adviser for– Wyeth, AstraZenica, Lawley

Pharmaceuticals

2.My research unit performs trials for the pharma, food & supplement industries


Agenda for tonightAgenda for tonight

1. HT – back again?2. Genitourinary symptoms3. Testosterone for women4. Non-oestrogen drugs for

flushes


49y old healthy woman having significant sweats, insomnia and aches and pains.

Is it safe for me to take HT?


Yes


Update of WHIUpdate 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


WHI 2007 – age specific WHI 2007 – age specific resultsresults“The absence of excess absolute risk

of CHD & the suggestion of reduced total mortality in younger women [aged 50-59 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.”


MJA June 2008


Take-Home messageTake-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


Compounded HTCompounded HT

1.No formal QC2.No safety studies3.No efficacy studies4.No endometrial studies5.Three cases of endometrial

cancer reported (MJA 2007; 187 [4]:244-5)


60y woman with recurrent UTIs and severe dyspareunia


Australian surveyAustralian 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


Multicultural Menopause Multicultural Menopause study, Sydney 2006study, Sydney 2006

1. Studied 5 ethnic groups in Sydney

2. Focus groups, (culturally sensitive)

3. Surveys using MENQOL (translated and checked)


Vaginal drynessVaginal dryness

Menopause status

Pre- Peri- Post- P value

ChineseThaiLebaneseIndianGreek

35%24%18%7%7%

90%41%43%54%17%

63%75%79%32%31%

<0.001<0.01<0.05<0.01<0.05


Prevalence of sexual Prevalence of sexual symptomssymptoms

Decline in sexual desire

Avoiding intimacy

ChineseThaiLebaneseIndianGreek

48%76%69%38%45%

44%46%54%32%40%


Genitourinary symptomsGenitourinary 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


Update on sexuality & Update on sexuality & hormoneshormones


OestrogenOestrogenIncreasedIncreased DecreasedDecreased1. Sexual

activity2. Enjoyment3. Desire4. Arousal5. Satisfaction6. Vaginal

lubrication7. Feeling

attractive

1. Dyspareunia2. Vaginal

dryness3. Sexual

problems

Menopause, 2004; 11:749-65


Testosterone updateTestosterone update1. 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.


Testosterone updateTestosterone 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.”


OthersOthers1. 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-14523?


Non-hormonal drugs for Non-hormonal drugs for flushesflushes

Nelson et al. JAMA 2006; 295, 17 :2057-Nelson et al. JAMA 2006; 295, 17 :2057-20712071SSRI & SNRI meta-analysisSSRI & SNRI meta-analysis

Paroxetine inhibits CYP2D6 & reduces some of tamoxifen’s metabolites

Nelson et al. JAMA 2006; 295, 17 :2057-Nelson et al. JAMA 2006; 295, 17 :2057-20712071Clonidine meta-analysisClonidine meta-analysis


Non-oestrogen drugsNon-oestrogen drugs

1.Gabapentin2.Three in phase 3,4 testing

– “a derivative of an antidepressant”

– “a derivative of gabapentin”– “an antihistamine”


Black CohoshBlack Cohosh

1.Mixed studies– Mostly positive

2.Most studied extract is Remifemin

3.Formal toxicology studies – safe4.Breast and uterus studies - safe5.Used for >50yr in Germany6.Idiosyncratic hepatic failure –

extremely rare


RemifeminRemifemin

Osmers, Obstet Gynecol 2005; 105, 1074-83

•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


Remifemin Plus [StJW]Remifemin Plus [StJW]Uebelhack(Obstet & Gynecol 2006; 107,

247-255)• 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


Rebbeck. Int J Can 2007; 120:1523-Rebbeck. Int J Can 2007; 120:1523-2828

• 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 0.27-0.82]– Consistent with cell culture studies

• Protective effect not seen for isoflavones, Dong quai or DHEA


CaseCase

45y woman who has had a double mastectomy for breast cancer. On Tamoxifen.

Problems – severe flushing, chest wall pain, severe vaginal dryness.

Nelson, Lancet 2008Nelson, Lancet 2008


1.Avoid aggravators2.Paced respiration3.Increase dietary soy and fibre4.Remifemin 2-4/d5.Some soy extracts6.SSRI or SNRI7.Clonidine8.Gabapentin

““I don’t want to take HT”I don’t want to take HT”

What’s new in menopause management? Associate Professor John Eden School of Women’s &...

Documents

Transcript of What’s new in menopause management? Associate Professor John Eden School of Women’s &...