The ageing woman

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The ageing woman

• Associate Professor John Eden

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Disclaimer

• Scientific adviser for
• Wyeth, AstraZenica, Lawley Pharmaceuticals
• My research unit performs trials for the pharma,
  food supplement industries

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Cases for today

• HT back again?
• Genitourinary symptoms
• Testosterone for women
• Non-oestrogen drugs for flushes

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• 47y old healthy woman having significant sweats,
  insomnia and aches and pains.
• Is it safe for me to take HT?

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• Yes

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Update of WHI

• 2002
• Stop HRT see your doctor
• Average age 68Y, gt5y 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

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WHI 2007 age specific results
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.
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Take-Home message

• HT is safe for most women lt60y
• Be cautious about starting HT in women gt65y with
  no symptoms!
• Long-term flushers patch plus Mirena?
• HT is not an anti-aging therapy
• HT and skin?

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• 60y woman with recurrent UTIs and severe
  dyspareunia

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Australian survey

• Only 9 of Australian women recognized vaginal
  dryness as a treatable menopausal symptom
• Of those who had the symptom, 77 rated it as
  moderate or severe.
• Vaginal dryness increases with age

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Multicultural Menopause study, Sydney 2006

• Studied 5 ethnic groups in Sydney
• Focus groups, (culturally sensitive)
• Surveys using MENQOL (translated and checked)

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Vaginal dryness
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Prevalence of sexual symptoms
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Genitourinary symptoms

• The impact of oestrogen lack on the bladder and
  vagina
• Safety of topical estrogens
• Are they absorbed?
• Vulval care
• Avoid soap
• Use moisturizers (Sorbolene, Replens
• Vegetable oil Sylk

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Update on sexuality hormones
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OestrogenIncreased Decreased

• Sexual activity
• Enjoyment
• Desire
• Arousal
• Satisfaction
• Vaginal lubrication
• Feeling attractive

• Dyspareunia
• Vaginal dryness
• Sexual problems

Menopause, 2004 11749-65
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Testosterone update

• 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.
• Total testosterone levels in women in their 40s
  are about 50 lower than that of women in their
  20s.
• Bilateral salpingo-oophorectomy, in both pre and
  postmenopausal women results in an immediate 50
  reduction in circulating serum testosterone
  levels.

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Testosterone update

• Testosterone cream or patches will increase
  testosterone levels in women.
• RCTs show a statistically significant increases
  in sexual activity but is it clinically
  significant. FDA says, No.

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Others

• Peripheral acting agents
• PDE5 inhibitors dont work
• VIP?
• Topical PGE1 agonists?
• NO agents?
• Central acting agents
• Apomorphine?
• Melanocortin agonists?
• 5HT1A agonists Flibanserin, OPC-14523?

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Non-hormonal drugs for flushes
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Nelson et al. JAMA 2006 295, 17 2057-2071SSRI
SNRI meta-analysis
Paroxetine inhibits CYP2D6 reduces some of
tamoxifens metabolites
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Nelson et al. JAMA 2006 295, 17
2057-2071Clonidine meta-analysis
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Non-oestrogen drugs

• Gabapentin
• Three in phase 3,4 testing
• a derivative of an antidepressant
• a derivative of gabapentin
• an antihistamine

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Barbara Gross Research Unit

• More than 20 studies
• 14 staff
• Broad research interests
• Male Osteoporosis study