Dr Helen Roberts MB, MPH, FAChSHM
Senior Lecturer Women’s Health
University of Auckland
Research Manager FPA

27,000 men and women aged 40-80 years in 29 countries

• For women lack of interest in sex was the most common “dysfunction”
• Chronic medical conditions –BP, heart disease, depression, stroke, hysterectomy did not influence likelihood of “dysfunction” in women

• Australian study of 474 women
• Low incidence of sexual distress-5.7% of women
• Higher in younger women
• Indifference to sexual frequency rose from
27% in age group 40-49 to 72% in 70-79 yr old
Howard JR et al Climacteric 2006;9(5):355-67

Dr Rosie King on lack of interest in sex, lack of libido, lack of desire
• Lack of libido is not necessarily a sexual
“dysfunction”
• There are often very compelling reasons why a woman’s desire should be low
• Common inhibitors of desire include fatigue, stress, painful sexual activity and relationship problems
• “after all if you don’t like your partner why would you want to have sex with them?”

• Decrease in progesterone with decreasing ovulatory cycles
After menopause
• decrease in estrogen production by the ovaries
• testosterone aromatised to estradiol/estrone in peripheral tissues and target organs (brain, breast, bone, genitalia)

In younger women testosterone produced
• Ovaries (25%)
• Adrenals (25%)
• Both also produce prohormones eg DHEA and androstendione
• These are converted to estrogen and testosterone (50%) in peripheral tissues/target organs
• Circadian variation-peak T early morning
• Main production of T midcycle

• Ovaries still produce some testosterone
• Adrenals still produce testosterone
• Both still produce some prohormones
• So not a marked decline at menopause
• Also as estrogen declines after menopause this can decrease in SHBG and increase free testosterone
• And rise in LH at menopause may stimulate the ovarian interstitial cells to produce testosterone
• Testosterone levels fall steadily from the age of
20-30 onwards

• Flushes-80% of women -20% severe
• Genitourinary symptoms
• Lack of estrogen –vaginal atrophy, decreased glycogen and lactobacilli, increased vaginal pH
• More intermediate and parabasal cells (KPI)
• However dyspareunia may not always follow
• 50% of women
• No universal sexual decline at menopause

• Immediate drop in both estrogen and androgen production
• Women usually more severe symptoms – flushes, fatigue and reduced sense of wellbeing
• Surgical menopause is associated with lower sexual desire and decreased arousal and frequency than for natural menopause
Dennerstein J Sex Med 2006;3:212-22

• Many women report little or no libido or sexual desire
• For some women desire only occurs when sexually aroused
• Some women do not experience orgasm but still enjoy sexual activity
• The genital response in women is a highly automated, unconscious reflex, occurs promptly within seconds of the stimulus and is mediated by the autonomic system
• But potentially independent of subjective sexual excitement

Dr Rosie King on lack of interest in sex, lack of libido, lack of desire
Categories of desire problems
• Primary low libido - never experienced much sexual desire
• Secondary inhibited sexual desire
• Desire discrepancy-inevitable in long term relationships

• Initiatory -horny + feel motivated to initiate sex
• Receptive -horny + will engage if partner initiates
• Available don’t feel horny but prepared to engage in sex
• Neutral -no lust and can take it or leave it
• Disinclined -not at all interested
“ Concerns about sexual desire can be traced to society’s dictate that the only normal level of sexual desire is initiatory”
Rosie King

• Very long, well-documented and quite extraordinary history of medicalisation
• Victorian era
“respectable women were regarded as not particularly sexual and if they enjoyed sex were in danger of hospitalization for insanity or subjected to clitoridectomy”
Bancroft J Archives of Sexual Behaviour 2002;31:451-6

• In 2003 an international committee redefined women’s sexual
“dysfunction” and included personal distress as an essential component
• Female Sexual Arousal Disorder –”the persistent or recurrent inability to attain or maintain sufficient sexual excitement, causing personal distress”
• Hypoactive Sexual Desire disorder-”the persistent or recurrent deficiency (or absence) of sexual fantasies, and/or desire for, or receptivity to, sexual activity, which causes personal distress
• Distress about sexuality is often higher in younger women 40-49 and decreases with age
• More distress about sexuality in women who had a partner
Howard JR et al Climacteric 2006;9:355-367

• Women’s sexual function is highly dependant on partner related factors
Lorraine Dennerstein Ann Rev sex 2003;40:266-76
• Best predictors of sexual distress are markers of general emotional wellbeing and the emotional relationship with the partner during sexual activity
Bancroft Arch Sex Behav 2003;32:193-211

4 factors strong correlation
• Mental and emotional health including sexual self image
• Feelings for partner in general and at time of intercourse
• Expectations regarding the future of the relationship
• Past sexual experiences

• Health-medical and psychological conditions and their Rx
• Partner’s sexual function
• Duration of relationship

• So there has been reconceptualisation of women’s sexual response
• Focus is no longer solely on initial sexual desire
• Many reasons and incentives that motivate women to accept or instigate sex with a partner

• Estrogen involved with vaginal elasticity and lubrication
• Increased vaginal blood flow and epithelial thickness, reduced pH and increased secretions
• For postmenopausal woman improves dyspareunia and sensitivity of vulval tissues to sexual stimulation
• Night sweats, poor sleep pattern and tiredness may all contribute to lack of libido

th
• !000 women over the age of 35
• 44% of these had vaginal dryness / atrophy
• 88% of these said it was causing them problems
• 47 % say they avoided having sex because of this
• 70% of the women said that they did not know that there were therapies to relieve vaginal dryness

• Not self limiting-may need long term treatment
• Vaginal estrogen better than oral
• A level evidence for vaginal atrophy
• B level evidence for recurrent UTIs
• Replens -B level evidence - atrophy/ UTIs
• Replens-Gladstone Pharmacy Parnell Auckland
• Use 3 times per week cost $37 /month
• Useful for women with previous breast cancer

• Ovestin cream/pessary-oestriol 0.5 mg
• Funded- so cost $15 for 3/12
• Vagifem-estradiol 25 mcg vaginal tabs
• Not funded- cost $75 for 30 tabs but Mercy pharmacy $47.80 + courier (09-6235703)
• Each night PV for first 2 weeks the twice weekly
• Takes 4-6 weeks to work
• Estring:vaginal ring:90 days-Pfizer under Section
29.Cost $75 + pharmacy charge (0800736363)

• Systemic absorption small
• Vagifem:E 2 levels in normal postmenopausal range
NAMS position statement
• Progestogen not generally indicated
• Insufficient data to recommend annual endometrial surveillance in asymptomatic women
• Continue Rx for women as long as symptoms remain
Notelovitz Obstet Gynecol 2002;99:556-62
NAMS Menopause 2007;3:357-69

2 recent large studies in pre and peri menopausal women have failed to find a correlation between sexual function and total testosterone, free testosterone or for androgen index
Santoro A et al. Clin Endocrinol Metab 2005;90:2004-63
Davis SR et al. JAMA 2005;294:91-6

• If the major hormonal production after menopause is intracellular and only a small % leaks back into the blood stream
• ? Serum levels useful-should we be measuring androgen glucuronides which are a marker for intra and extra cellular testosterone
• Also immunohormone assays for testosterone not particularly accurate for women
• Gold standard equilibrium dialysis, isotope dilution spectometry-expensive
• ADHB total testosterone measure by immunoassay
• And free testosterone calculated

Does testosterone replacement help?
Cochrane Review CD004509-August 2005
• Addition of testosterone to HRT(E or E+P) to surgically and naturally menopausal women
• Oral,sublingual,implant(50,100mg),transdermal(150,300,450 mcg)
• Interventions grouped together
• Only 3 of the studies included women with impaired sexual function at base line
• Beneficial effects on sexual function-coital frequency, responsiveness, libido (desire) for all types of menopause
• HDL reduction with implants and oral
• No effect on wellbeing, fatigue, bone, body composition, menopausal symptoms, cognition, hirsuitism, acne-though many studies did not report these outcomes
• No evidence for perimenopausal women

• Potential side effects of acne, facial hair, deepening of voice, weight gain
• Adverse effects on lipids
• Increased hematocrit and abnormal liver function with high dose
• Evidence on long term effects needed breast cancer (aromatisation to estrogen), insulin resistance - the metabolic syndrome coronary heart disease
• Need studies for E+T v T alone
• And for T v placebo

• Nurses’ Health Study
• 24 yrs of follow up -1,359323 person yrs
Postmenopausal women
Natural menopause
Estrogen
E+P
E+T
1.15 (1.05-1.27) 1.23 (1.05-1.44)
1.58 (1.44-1.73) 1.66 (1.49-1.84)
1.77 (1.22-2.56) 2.48 (1.53-4.04)
Tamini RM et al. Arch Intern Med 2006;166:1483-1489

• 4 further studies with transdermal testosterone
• All given to estrogen replete- surgically menopausal women
• SS increase in desire -with 300mcg patch but not 150
(400 no better than 300)
• No androgenic side effects
• Overall effect –one more episode of satisfying activity per month-1.9 v 0.9 extra with placebo
• If take out women on oral CEE -2 extra per month
• However this maybe important for women
J Clin Endocrinol Metab 2006;91:3697-3710

• FDA 2004-voted in favour of efficacy for female hypoactive sexual desire in surgically menopausal women
• Not approved due to lack of long term safety data
• Approved by European Agency for the
Evaluation of medicinal Products

• Recommend against making a diagnosis of female androgen deficiency in women because of a lack of a well defined clinical syndrome and normative data on testosterone levels across the lifespan
• Evidence of short term efficacy for testosterone mainly in surgically menopausal women
• Recommend against generalised use of testosterone by women as indications are inadequate and evidence of safety data in long term studies is lacking
• Also reservations about long term estrogen therapy
J Clin Endocrinol Metab 2006;91:3697-3710

• Therapeutic use of testosterone is off label
Not recommended for use in women with
• Breast or uterine cancer
• Cardiovascular disease
• Liver disease
• Testosterone should be administered at the lowest dose for the shortest time that meats treatment goals
NAMS position statement 2005

Do women respond differently to hormones?
• Most women vulnerable to non hormonal changes
• ? Subgroup of women who may be vulnerable to changes in sex hormones as they age
• Gene polymorphism of E receptors and of genes producing aromatase and 5 α hydroxylaseneeded for the intracellular production of estradiol and testosterone
• Some research already shows that flushes are more likely in women with a particular type of gene polymorphism

Viagra for women

Sildenafil citrate in postmenopausal women
• Results in calcium influx to corpus cavernosa of both penis and clitoris
• Causes relaxation of smooth muscle
• Improves clitoral and uterine blood flow
• Peak levels in 1 hr and half life 4.5 hrs
• Small RCTs suggest possible benefit (25,50mg) for arousal/orgasm for premenopausal women (one of these in women on SSRIs)
• One RCT in postmenopausal women receiving estrogen
• 10,50,100mg-no improvement in sexual response
Modelska K and Cummings S. Am J Obstet Gynecol 2003;188:286-93)

• RCT in postmenopausal women with
“FSAD” receiving E + T – improvement in sexual arousal, orgasm and satisfaction
• Orgasm satisfaction 8% increase with placebo and another 7% increase with Viagra (100mg)
Berman JR et al. J Urol 2003;170:2333-38

• Desire is interest in sex, so it's libido, it's lust, it's hunger for sex. Desire is moderated through the desire centres in the brain.
Arousal on the other hand is getting turned on and this is where you get the physiological changes with increased blood flow. You get two or three times the amount of blood flow through the genitals during sexual arousal.

• Viagra acts on arousal, by increasing blood flow to the sexual organs.
In men, it works incredibly well. But despite extensive trials around the world, in March,
Pfizer announced Viagra for women was a dud.
So why didn't it work? One surprising answer came up during an unusual test.

• Dr Rosie King:
What we're seeing here is some erotic video that was made for women, specifically for women.
Narration:
Women were given Viagra, and shown pornography while their genital blood flow was recorded.
Dr Rosie King:
And what was amazing is that although women said they weren't turned on by this sort of material, the physiological response, the measurement showed that they definitely were.
Jonica Newby, Reporter:
So are you saying that women could actually take viagra, get the physical arousal, and not even be aware of it, not know.
Dr Rosie King:
Oh, absolutely.
Narration:
It's all to do with what Viagra treats - it treats a mechanical, blood flow problem.

• Helps flushes and vaginal dryness
• Tibolone -decreases SHBG-increase in free testosterone
• RCT of tibolone v E+P-greater improvement coital frequency and satisfaction
• Two small RCT v placebo no difference higher levels of sexual fantasy but not activity
• Need RCT v placebo to assess effects in women complaining of low sex drive
Maturitas 2005;51:21-28
• Long term risks of tibolone-RR stroke 2.3 v placebo
LIFT study BMJ 2006;332:667

• Mechanisms in the brain for both sexual excitation and for inhibition of sexual response
• This sees inhibition of sexual response for the majority as an adaptive mechanism –not a dysfunction
• Women show a significantly higher mean level of inhibition than that found in men
• ? Women have a greater need for inhibitory mechanisms because of their greater investment in reproduction and parenting
• The women may not be responding sexually because it is adaptive for her not to do so
• Such lack of response should not be seen as dysfunction

“Until we can distinguish between such adaptive inhibitions of response and those that are maladaptive dysfunctions, we will have difficulty in predicting when pharmacological treatment will be helpful”
John Bancroft

Ginkgo
• no evidence for women
Yohimbebark from West Africa
• Adrenoreceptor agonist
• Vasodilation
• no evidence for women

Horny Goat Weed inhibits PDE-5 enzyme similar to Viagra
• no evidence for women
Damiana-Mayan herb
• no evidence for women

• Interest in sex for women only decreases slightly with age
• Vaginal estrogen can be used long term if intercourse painful
• HRT plus testosterone may help surgically menopausal women but need to consider risk benefit
• Viagra not useful
• More work needed with tibolone

Doctor-where did my libido go?
Google RANCOG, click publications, then
O+G magazine, then Spring 2006 issue
• Men usually anticipate that they will continue to enjoy
‘desire –driven sex”
• If women wait until they feel overcome by lust lovemaking will rarely happen
• Women often use a practical strategy known as
“decision-driven sex”
• Reward for herself- as satisfying sexual activity can be pleasurable
• … and goodwill towards her partner-”goodwill from a happy relationship where the woman’s emotional needs are being met”
Rosie King

Australian oysters do it longer
A group of NSW oyster farmers are attempting to chemically boost the aphrodisiac qualities of their oysters — by feeding them Viagra .
The farmers have patented the process and are now preparing to export to the
Asian market, which they estimate could be worth $220 million dollars