medical basis for gender medicine
TRANSCRIPT
MEDICAL BASIS FOR GENDER MEDICINE
Yuval Kaufman MDHead of the Multidisciplinary Center for the Treatment of Endometriosis
Dept. of Ob/Gyn, The Lady Davis Carmel Medical Center, Haifa, Israel
www.gynsurg.co.il [email protected]
GENDER MEDICINE
➢ Personalized medicine / Patient-centered / Precision medicine
➢ Includes:
➢ Sex (biological)
➢ Gender (social)
➢ Deals with all organs and disease patterns, not only with “female-specific” (e.g. breast,
uterus) or with “male-specific” (e.g. prostate)
➢ Includes:
➢ Health-related behaviors and prevention
➢ Symptoms
➢ Disease
➢ Diagnosis
➢ Therapy
➢ Rehabilitation
INFLUENCE FACTORS
➢ Bio-psycho-social health model - gender is influenced by
➢ Biology
➢ Social influences
➢ Education
➢ Individual life situations
➢ How power is distributed
➢ Who has the resources
SOCIAL INFLUENCES
➢ Example - women’s and men’s magazines:
➢ Food-related articles for men – barbecues and beer
➢ Health articles for men – potency, muscle building
➢ Food-related articles for women - dieting, healthy
recipes
➢ Health articles for women - fitness plans in order to
achieve a bikini-perfect figure
XX AND XY
➢ Biological differences are based on genes, sex chromosomes
and sex-specific hormones
➢ X chromosome carries the majority of genes for heart, brain,
and immune system
➢ Women have a stronger immune system than men:
➢ Less at risk for infectious diseases - Mycobaterium
tuberculosis, Amoebic liver abscess, Malaria, …
➢ Better antibody production after vaccination
➢ 1:2 men and 1:3 women lifetime risk of cancer
➢ 1:3 men 1:6 women probability of dying from cancer
XX AND XY
➢ But…
➢ More autoimmune diseases - hyper- or hypothyroidism,
multiple sclerosis and rheumatic diseases.
➢ Y chromosome mainly contains genes that are related to
sexual function
GENETICS & EPIGENETICS
➢ Epigenetics – control of gene expression
➢ Male and female embryos start responding to gender-specifically
inside the womb
➢ Epigenetics - fetal programming through environmental factors,
stress, nicotine, alcohol, etc
➢ Examples:
➢ Mother smokes during pregnancy - risk of hypertension in
boys is much higher than in girls
➢ Gestational diabetes - boys also have a higher risk of
developing diabetes, but the Girls are more likely to be
overweight
➢ Female premature babies have better survival than males
WOMEN VS. MEN – ANATOMY AND PHYSIOLOGY
➢ women are usually smaller, their body mass index (BMI) is lower
➢ smaller organs
➢ more body fat (even newborn girls have a higher percentage of
body fat compared to their male counterparts)
➢ smaller percentage of muscles
➢ less stomach acid
➢ slower kidney filtering
➢ less body water (subject to cycle-dependent fluctuations)
➢ Differences in liver enzyme activity (typical example: alcohol
works differently in women and men)
➢ sex hormones (estrogen, progesterone vs. testosterone)
OVERVIEW
➢ Affects how drugs work:
➢ Soluble in water or fat
➢ Broken down by the kidney or liver
➢ Influences effect and side effect.
WOMEN VS. MEN – METABOLISM
➢ Women use less energy (basal metabolism) because they have fewer
muscles – more fat gain for the same diet
➢ Less liver fat
➢ Less belly fat, therefore less risk for diseases associated with belly fat
➢ More favorable fat cell hormones: Women have more favorable fat
on hips and legs, which protects against diabetes and cardiovascular
disease.
➢ Better insulin sensitivity
➢ Lower fasting blood sugar level
➢ Gastric absorption of glucose is slower in women
➢ More intense activation of the stress axis (brain-adrenal axis)
WOMEN VS. MEN – SEX HORMONES
➢ Hormone fluctuations depending on the cycle:
➢ medications may have different effects depending on the cycle
➢ asthma attacks may occur differently depending on the cycle.
➢ Menopause – no estrogen protection:
➢ change in metabolism
➢ worse blood sugar and fat metabolism
➢ higher blood pressure and a redistribution of body fat (to a
masculine form).
➢ Andropause (age 50 plus) - metabolic changes are fewer
➢ Women have a longer life expectancy but have a smaller amount
of healthy years
OVERVIEW
OVERVIEW
WOMEN VS. MEN – CARDIOLOGY
➢ Gender medicine started out by observing heart
diseases
➢ Young women's vessels are protected by estrogen
➢ Cardiovascular diseases in women are often symptom-
free and fatal
➢ Female patients are on average 10 years older than
males
➢ Women are running a 50% higher risk of dying in the
first year after a heart attack
➢ Twice as high a risk of having complications after
bypass surgery
➢ Mortality increases among women under 55 (has
increased in recent years)
WOMEN VS. MEN – CARDIOLOGY
➢ women seldom display chest pain - Pain is often of
non-specific, not sharp- heart attack is often
unrecognized
➢ Stroke
➢ Risk factors are rarely detected in women
➢ In men, hemiplegia is the typical symptom, women
more often display dizziness, confusion and speech
disorders.
WOMEN VS. MEN – DIFFERENCES IN HEALTH BEHAVIOR
➢ For the same disease may differ in:
➢ disease morbidity
➢ risk factors
➢ onset age
➢ clinical phenotype
➢ Women are more likely to see a doctor and attend check-ups
➢ Men consider exercise to be healthier, while women set great store
by a healthy diet
➢ Women take fewer steps during the day, regardless of age and
weight
WOMEN VS. MEN – DIFFERENCES IN HEALTH BEHAVIOR
➢ Smoking and alcohol abuse WERE common among men and are
STILL responsible for a substantial part of the gender gap in life
expectancy. The situation is changing.
➢ Stress due to multiple exposures in job and family or as a single
parent, affects mainly women
➢ Caring is the women's thing: 80% of all nursing occupations are
carried out by women, this also applies to care activities within the
family
➢ Depression is diagnosed twice as often in women
➢ Suicide is 2-3 times more common in men - many undiagnosed
depression cases in men
WOMEN VS. MEN – SMOKING
➢ Women smoke less
➢ Smoking has more negative effects on women than on men
➢ Women smoke differently and for other reasons, such as stress and
weight management
➢ Men have less difficulty quitting
➢ Smoking leads to an increased risk of complications in women:
➢ heart attack/stroke (25% higher than in men)
➢ osteoporosis
➢ cancer
WOMEN VS. MEN – MEDICATIONS
➢ Androcentric medicine
➢ female medicine – studies on gynecology and reproductive
medicine, or particular types of cancer (Breast, thyroid)
➢ Women are underrepresented in the early stages of clinical
trials
➢ women in their reproductive age are excluded from trials due
to rapid hormonal changes and possible pregnancy
➢ females were just one third of the enrolled patients in clinical
trials performed between 2002 and 2007 to evaluate
cardiovascular devices
WOMEN VS. MEN – MEDICATIONS
➢ male sex also prevails in preclinical studies on animals -
female animals have higher biological variability compared
to male animals – caused by sex hormone fluctuations
➢ gender-specific pre-clinical models will increase gender-
oriented therapeutic protocols
➢ “Medicine as it is currently applied to women is less
evidence-based than that being applied to men”, Nature
2010
WOMEN VS. MEN – MEDICATIONS
➢ Most medications withdrawn from the market pose a greater
health risk for women.
➢ Single medication for which FDA prescribes different intake
routines - the sleeping pills Zolpidem should be prescribed to
women only in half a dose (5mg instead of the previous 10mg).
➢ Trend towards gender medicine:
➢ Understanding molecular, genetic and epigenetic bases of
complex diseases
➢ Personalized pharmacogenetic approach to drug
design/prescription
➢ Several diseases are now faced in a tailored fashion
WOMEN VS. MEN – PAIN
➢ Physical, psychic and socio-cultural components
➢ 85000 adults in 17 countries - chronic pain symptoms of any kind -
45% of women, 31% of men
➢ Females feel pain more intensely with a lower threshold than men
➢ Growing up - girls often feel free to cry over small injuries, while
boys feel extra pressure to hold back the tears
➢ medical staff treat a disease more seriously when a man reports it
even if the symptoms are the same
WOMEN VS. MEN – PAIN
➢ women are more likely than men to develop anxiety or depression
that can increase feelings of pain
➢ E increase pain with concentration-dependent mechanisms, T
reduces the sensitivity to chronic pain
➢ At puberty – increased pain perception in women – sex differences
disappear in menopause
➢ NSAIDs more effective on men, Opiates more on women (2.5 times
more!)
Ancient Disease
Only been studied in the last 50 years
One of the most studied
diseases
Pathogenesis still unknown
Billions spent each year on
diagnosis and treatment
Most women remain
undiagnosed
Big pharma companies looking for
medical solution
Treatment hasn’t changed
in the last 40 years
ENDOMETRIOSIS
WHAT DO WE KNOW?
➢ What is endometriosis?
➢ a common, benign, inflammatory, generally gynecologic disease that
includes the presence and growth of dysfunctional endometrial-like
glands and stroma often with reactive fibrosis and muscular metaplasia
outside the uterus
➢ Includes➢ Adhesions
➢ Deep endometriosis
➢ Endometriomas
➢ Involvement of GI, GU, nerves
➢ Causes subfertility
➢ Location:➢ Gravity dependent
➢ Distal lesions – pleura, pericard , brain, extremeties, etc.
ENDOMETRIOSIS – DISEASE OF MANY FACES
➢ Complex enigmatic disease
➢ Different types of patients✓ Age
✓ Needs
✓ Location
✓ symptoms
PREVALENCE
➢ Mostly fertility age women
➢ 8-10% of these women
➢ Worldwide 180M
➢ Israel:
➢ 1.7M women age 15-50
➢ Prevalence probably similar to world
➢ Estimated prevalence in Israel 150K women
PREVALENCE
➢ Select populations:
➢ Infertility patients 30-50%
➢ Chronic pelvic pain – 50-60%
➢ CPP adolescents – 70%!!
➢ Endometriosis – the “invisible disease”
➢ Lag time – 8-9 years
➢ Early diagnosis critical:
➢ Easier to treat
➢ Irreversible fertility damage
➢ Patient suffering
DIFFERENT TYPES OF ENDOMETRIOSIS
Peritoneal Adolescent
Bladder
POD obliterationBowel
Ovarian
Adenomyosis
GOALS FOR THE MANAGEMENT OF ENDOMETRIOSIS
3
4
Taylor HS. Medscape Education 2017. Available at: https://www.medscape.org/viewarticle/876964.
Reduce pain
Improve quality of life
Prevent chronic pelvic pain
Preserve or improve fertility
↓
↓QoL
WHAT ARE WE TREATING ?
INFERTILITY SYMPTOMS
BOTH
TREATMENT
Indications for treatment➢ Medical:
✓ Pain
✓ Prevent recurrence after surgery
✓ Avoid proliferation
✓ Prior to IVF (GnRHa or OCs)
➢ Laparoscopy:
✓ Failed medical treatment
✓ Fertility
▪ Patients wishing to conceive without ART
▪ Failed IVF
✓ Suspicious pelvic finding – e.g. large or atypical endometrioma
✓ Unclear diagnosis
Suppress
Excise
DIAGNOSIS – SIGNS & SYMPTOMS (1)*
* Symptoms more frequent during menses and ovulation
Shoulder pain
Dysmenorrhea
Dyspareunia
Rectal pain
Flank pain
Dysuria Scar pain (c-section, episiotomy)
Sciatica
Back pain
Chronic pelvic pain
Dyschezia
MEDICAL TREATMENT
➢ Hormonal suppression:
➢ During pregnancy and menopause – symptom improvement
➢ Good for treating symptoms and avoiding recurrence or progression
➢ Symptoms recur on discontinuation
➢ Works mostly on superficial lesions
Yuval Kaufman MDHead of the Multidisciplinary Center for the Treatment of Endometriosis
Dept. of Ob/Gyn, The Lady Davis Carmel Medical Center, Haifa, Israel
www.gynsurg.co.il [email protected]
MEDICAL BASIS FOR GENDER MEDICINE