Sex and the older woman (person) Dr Helen Roberts MB, MPH, FAChSHM Senior Lecturer Women’s Health University of Auckland Research Manager FPA

27,000 men and women aged years in 29 countries

Results of the Global Study 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 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 to 72% in 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?”

So what about hormones- do they change as women age?

Hormonal changes as women age 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)

What about testosterone? 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

Does testosterone decrease at menopause? 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 onwards

What symptoms do women get at menopause? 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

What about surgical 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

What is normal sexual function anyway-are we all the same? 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

Levels of sexual desire 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

The medicalisation of female sexual dysfunction: the need for caution 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

Medical definitions 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 and decreases with age More distress about sexuality in women who had a partner Howard JR et al Climacteric 2006;9:

The other person involved Women’s sexual function is highly dependant on partner related factors Lorraine Dennerstein Ann Rev sex 2003;40: 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:

Factors which correlate with sexual function in women 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

Other factors that correlate with sexual function in women Health-medical and psychological conditions and their Rx Partner’s sexual function Duration of relationship

So …. 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

Back to hormones 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

Reuters reporting in Weekend Herald August 18 th 2007 !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

Genito –urinary symptoms 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

Vaginal estrogens 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 $ courier ( ) 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 ( )

Long term Rx with vaginal E 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: NAMS Menopause 2007;3:357-69

Testosterone levels and libido 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: Davis SR et al. JAMA 2005;294:91-6

Are we measuring the right thing? 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 CD 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

What are the risks of testosterone replacement? 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

RR breast cancer with testosterone Nurses’ Health Study 24 yrs of follow up -1, person yrs Postmenopausal women Natural menopause Estrogen1.15 ( )1.23 ( ) E+P1.58 ( )1.66 ( ) E+T1.77 ( )2.48 ( ) Tamini RM et al. Arch Intern Med 2006;166:

Since Cochrane review 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:

Approval for Intrinsa 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

Endocrine Society Clinical Practice Guideline 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:

North American Menopause Society –position statement 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 5α hydroxylase- needed 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)

Sildenafil-Viagra 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:

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.

Tibolone: Report from International Tibolone Consensus Group 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

Kinsey Institute modelling 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

So………. “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

Other therapies Ginkgo no evidence for women Yohimbe- bark from West Africa Adrenoreceptor agonist Vasodilation no evidence for women

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

So where does that leave us? 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

But watch out for the marketing…………..

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 Australian oysters do it longer