Menopause typically occurs around age 51 and is defined as the cessation of menstrual periods for one year. It marks a major decline in estrogen and progesterone levels. Common symptoms include hot flashes, sleep disturbances, mood changes, and vaginal dryness. Long-term risks of estrogen deficiency include osteoporosis, heart disease, and cognitive decline. Historically, hormone replacement therapy (HRT) was widely used to treat menopausal symptoms but large studies in the early 2000s like the Women's Health Initiative found increased risks of breast cancer and heart disease with HRT use. This led to a reevaluation of HRT recommendations focusing on using the lowest effective dose for the shortest duration possible to manage menopausal symptoms
Uterus (womb) as an organ is pivotal not only to giving birth, but also to the overall well-being of women and their physical, emotional, and sexual health.
This seminar explores the potential connection between two inositol stereoisomers supplements and improvements in insulin sensitivity and various metabolic parameters.
Uterus (womb) as an organ is pivotal not only to giving birth, but also to the overall well-being of women and their physical, emotional, and sexual health.
This seminar explores the potential connection between two inositol stereoisomers supplements and improvements in insulin sensitivity and various metabolic parameters.
Role of antioxidants in female infertility Dr. Jyoti AgarwalLifecare Centre
Role of antioxidants in female infertility Dr. Jyoti Agarwal
3 Concepts
Oxygen toxicity is an inherent challenge to aerobic life
Oxygen is essential for life.
Excess oxygen can have harmful effects.
When oxygen is metabolised in the body , it produces substances called FREE RADICALS which damage our cells.
PANEL DISCUSSION
MANAGEMENT OF PCOS - WOMB to TOMB
MODERATOR : Sharda Jain
PANELISTS : Dr.Chitra setia
Dr Puneet Arora
Dr. Ila Gupta
Dr. Rupam Arora
Dr. Archana Sharma
Dr. Sangeeta Gupta
Dermatologists
Dr. V.K. Upadhyay
Dr. S. Kandhari
Hypertensive Disorders in Pregnancy (HDP) represented 15.4% of total numbers of maternal death- the 4th main cause after obstetric embolism, PPH and other medical non HDP conditions
Role of antioxidants in female infertility Dr. Jyoti AgarwalLifecare Centre
Role of antioxidants in female infertility Dr. Jyoti Agarwal
3 Concepts
Oxygen toxicity is an inherent challenge to aerobic life
Oxygen is essential for life.
Excess oxygen can have harmful effects.
When oxygen is metabolised in the body , it produces substances called FREE RADICALS which damage our cells.
PANEL DISCUSSION
MANAGEMENT OF PCOS - WOMB to TOMB
MODERATOR : Sharda Jain
PANELISTS : Dr.Chitra setia
Dr Puneet Arora
Dr. Ila Gupta
Dr. Rupam Arora
Dr. Archana Sharma
Dr. Sangeeta Gupta
Dermatologists
Dr. V.K. Upadhyay
Dr. S. Kandhari
Hypertensive Disorders in Pregnancy (HDP) represented 15.4% of total numbers of maternal death- the 4th main cause after obstetric embolism, PPH and other medical non HDP conditions
Miscarriage is pregnancy loss before 22 weeks’ gestation based on the LMP or if gestation age is unknown, it is the loss of an embryo or a fetus of less than 500g.
Evaluation and options in Managing Subfertile CoupleEddie Lim
Subfertility - Failure to conceive within 12 months of
regular sexual intercourse without any form
of contraception.
Woman older than 35 years -- have not
conceived during a 6-month period of trying.
Endometrial hyperplasia - irregular proliferation of the endometrial glands with an increase in the gland to stroma ratio when compared with proliferative endometrium
Endometrial Ca - most common gynaecological maglinancy in the western country, endometrial hyperplasia as the precursor
Incidence of endometrial hyperplasia 3 folds higher than endometrial Ca
Fourth most common cancer in women in Peninsular Malaysia
Abnormal uterine bleeding can occur when a woman experiences a change in menstrual loss, or the degree of loss or vaginal bleeding pattern differs from that experienced by the age-matched general female population
AUB is not restricted to menstrual bleeding that is abnormally heavy, but includes bleeding that is abnormal in TIMING
Breast Cancer Essay examples
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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2.
Defined as cessation of menses for one year
Average age – 51 years old
Major milestone in majority of women
Menopause
3. Age-Related Changes of
Hormones in Women
Premenopause Perimenopause Postmenopause
Progesterone
Estradiol
50%
Progesterone deficit Age 40-50 yrs
Estrogen deficit Age 45-53 yrs
Androgen deficit Age 55-65 yrs
7. You look so flushed!
Did you just finish a
zumba class? I love
zumba!
8.
9.
Onset of Symptoms and Disorders
in Relation to Age and Menopause
Vasomotor Symptoms
Sleep Disorders
Menstrual Disorders
Mood Changes
Vaginal Atrophy
Dyspareunia
Skin Atrophy
Osteoporosis
Atherosclerosis
Coronary Heart Disease
Cerebrovascular Disease
40 yrs 50 yrs
Menopause
60 yrs
10. Age (years)
EstrogenSecre
40 45 50 55 60 65 70 ≥75
Development
of subclinical
disease
Urogenital symptoms
Cardiovascular disease
Short-term Symptoms Long-term Diseases
Cognitive decline
(Alzheimer’s disease)
Hot flushes
Mood, sleep, and/or
acute cognitive changes
Osteoporosis
Estrogen Loss and Manifestation ofEstrogen Loss and Manifestation of
Health Risks Over TimeHealth Risks Over Time
Prof. G. Rosano
11.
1. Periods, symptoms and contraception
Date of last menstrual period [could she be pregnant?]
Frequency, heaviness and duration of periods
Hot flushes and night sweats?
Vaginal dryness?
Other symptoms?
Contraception
History
12.
2. Personal or family medical problems
Breast/ ovarian/ bowel cancer in close family
members
Deep vein thrombosis or pulmonary embolism
Risk factors for heart disease and strokes?
Risk factors for osteoporosis
Other
History
14.
BMI
BP
Breast examination and pelvic examination if
indicated
Examination
15. “Every woman alive today has
the option of remaining feminine
forever,” he wrote. “No longer
need she fret about the cruel
irony of women aging faster
than men. It is simply no longer
true that the sexuality of a
woman past forty necessarily
declines more rapidly than that
of her husband.”
16. • HERS IHERS I
• HERS IIHERS II
• WHIWHI
• Million Women StudyMillion Women Study
• HERS IHERS I
• HERS IIHERS II
• WHIWHI
• Million Women StudyMillion Women Study
And the bubble bursts….
17.
A Long History of Hormone Replacement
Therapy
900-1500 1890 1928 1935 - 41 1943 60’s 70’s 80’s 90’s 2002 - 04
China: urine extract to treat “sexual debility” and keep women young
Europe: ovarian extracts used for “hysterical” women
Germany: estrogens found in “pregnancy urine”
EU/US: efficacy in hot flushes, bone loss
Conjugated estrogen pill developed
Menopause – a preventable disease
Estrogens cause endometrial cancer
Endometrium protected by progestogens
20-30% of women take HRT in US and EU
HERS, WHI, MW
lead to a HRT
reassessment
and a move to
LOW DOSE
18. Just over a decade ago:
Knowledge of a small increase in breast cancer but overall,
positive risk – benefit relation because of
• efficacy in menopausal symptoms
• prevention of osteoporosis and heart attacks
• probably prevention of stroke and Alzheimer‘s disease
• breast cancer on HRT was believed to have a better prognosis
History of HRT
19. What Happened?
After several decades of effective treatment with HRT
the results of a few but major studies are shaking the
world.
• HERS stopped after 5 years - no improvement in prognosis of CVD
• WHI stopped early, in July 2002 – increased risk of CVD
• Wisdom stopped early, end of 2002 - … because of WHI
• WHIMS data of the WHI memory study in May 2003 –
no benefit in cognitive function, potential worsening of dementia
• WHI data on breast cancer stage while on HRT, May 2003
• Million Women Study data on breast cancer
20. WHI and MW Studies
Extra breast cancer cases per 1000 HRT users
-7.0-5.00E only
51.50E only
1960E + P
10 years5 yearsNever usersMWS
1860E + P
7 years5 yearsNever usersWHI
Million Women Study Collaborators, Lancet 2003 Aug; 362: 419-27
WHI Investigators, JAMA. 2002 Jul 17;288(3):321-33
WHI Investigators, JAMA. 2004 Apr 14;291(14):1701-12
21. The PerceptionThe Perception
An increased risk of breast cancer was perceived
by the patients as the most worrisome.
Cardiovascular events were worrisome for authorities
and prescribers.
Breast Cancer
• 2nd leading cause of
cancer deaths in U.S.
women
• Over 46,000 women
die of breast cancer
annually
Cardiovascular Disease, the No. 1 Killer.
22. 1. Do Not Ignore It
How Do We Deal With theHow Do We Deal With the
Risk?Risk?
23. Randomised, placebo controlled trial
Placebo vs E alone vs E + P
E + P 16,608 women, mean age 63 years
E + P arm stopped at 5 years because of increased
breast cancer risk
E alone 10,739 women, mean age 64 years
E alone arm stopped at 7 years
Women’s Health InitiativeWomen’s Health Initiative
-- Level 1 evidenceLevel 1 evidence
WHI Investigators, JAMA. 2002 Jul 17;288(3):321-33
WHI Investigators, JAMA. 2004 Apr 14;291(14):1701-12
24. Million Women Study Collaborators, Lancet 2003 Aug; 362: 419-27
• Observational study ( hear say
only, mentioned the word
“estimate” 50 times)
• 1,084,110 women
• Completed questionnaire before
routine mammography
• Flagged on NHS Central
Registers
• Cancer registrations notified
• Deaths notified
Million Women StudyMillion Women Study
-- Level 2-III evidenceLevel 2-III evidence
25. On 31 May 02, the Data and safety monitoring board
recommended stopping the E+P vs Placebo trial after a
mean of 5.2 years of follow-up:
1. Invasive breast cancer test statistic exceeded
the stopping boundary for this adverse effect
2. Global index statistic supported risks exceeding benefits
All data on the major clinical outcomes up to 30 April 02
WHI - ResultsWHI - Results
WHI Investigators, JAMA. 2002 Jul 17;288(3):321-33
26. Risks – as Reported from the WHIRisks – as Reported from the WHI
Placebo (n = 8102), Prempro®
(n = 8506) at 5.2 years
Prempro®
vs Placebo Placebo Prempro®
Event Hazard Ratio Absolute Risk per
(95% CI) 10,000 Person-yrs
Breast cancer (known) 1.26 (1.00-1.59) 30 38 Δ + 8
Heart attack (NEW) 1.29 (1.02-1.63) 30 37 Δ + 7
Stroke (NEW) 1.41 (1.07-1.85) 21 29 Δ + 8
DVT (known) 2.07 (1.49-2.87) 13 26 Δ + 13
Hip fracture (NEW) 0.66 (0.45-0.98) 15 10 Δ - 5
Colorectal cancer (known) 0.63 (0.43-0.92) 16 10 Δ - 6
Level 1 evidence
WHI Investigators, JAMA. 2002 Jul 17;288(3):321-33
27. The chance for a woman of not getting breast cancer in a year of HRT use:
BrCa(+) BrCa(-)
No HRT use – 99.70% per year 30/10,000 9,970/10,000
HRT use – 99.62% per year 38/10,0009,962/10,000
so, her actual risk increases 0.08%
From WHI: To your patients
28. The chance for a physician to be confronted with a woman of breast cancer
attributable to HRT is 1 /1250 treated
If you treat per year, for a whole year:
100 women (2 per week), 1 in every 12.5 years
200 women (4 per week), 1 in every 6+ years
400 women (8 per week), 1 in every 3+ years
From WHI: To your patients
30. Incidence rates per 100,000 (age-standardized)
Worldwide 35.7
United States 96.7
Northern Europe 73.2
Western Europe 78.2
Southern Europe 56.2
Eastern Europe 49.4
Western Asia 27.9
Southeast Asia 25.6
Eastern Asia 18.1
Breast Cancer Incidence RatesBreast Cancer Incidence Rates
Krieger N. Am. J. Public Health 2002; 92:611
31. Breast Cancer Risk FactorsBreast Cancer Risk Factors
USA 2000 data, for all races,
19.5 cases of invasive breast cancer
per 1000 women aged 50 -64 years 9
0 5 10 15
WHI, E for 6.8 years on average 8
WHI, E+P for 5.2 years on average 7
Age >30 years at 1st delivery 6
Obesity (BMI >28.8) 5
Alcohol (30 to <60 g/day = 2-5 drinks) 4
Passive smoking 3
Heavy Smoking (>20 cigs/day) for 40 years 1
11.7
16.2
9.8
- 4.5
5.1
6.9
8.0
7.6
Additional invasive breast cancer cases
per 1000 women aged 50 to 64
Breast cancer in mother 2
32.
No good evidence of extra risk of
breast cancer with estrogen alone
Breast Cancer & ERT
WHI Investigators, JAMA. 2004 Apr 14;291(14):1701-12
33. Chronological Development
of Breast Cancer
Growth
1cm
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Years
2,5 cm1mm
Premammographic Mammographic
Window
Clinically detected
Breast
Tumor
Speroff L et al., Clin Gyn end and inf 1999; 16: 631
34. Indications for HRTIndications for HRT
Estrogen deficiency symptoms
in postmenopausal women (using the lowest effective
dose for the shortest duration)
Prevention of osteoporosis
in postmenopausal women
at high risk of future fractures
who are intolerant of, or contraindicated for, other
medicinal products approved for this
Solvay SmPC, issued 29 March 2004
35. Who could, and should use HRT?Who could, and should use HRT?
36. Women with Hot Flushes
and Night Sweats
“Short term” Treatment
Women with vaginal
atrophy
HRT improves quality of life
The Health of women on HRT is regularly checked.
37. But as Women Differ ByBut as Women Differ By
• Genetics
• Age and stage of menopausal (peri- or post-menopausal)
• Symptoms and needs (vasomotor symptoms, urogenital
atrophy, prevention of osteoporosis)
• Risk factors (e.g. for breast cancer, thromboembolism)
• Preferences (form of administration, withdrawal bleeds)
• Habits (life style, dietary factors)
• Fears
Individualize Therapy
45.
Thank You!
Dr. Christine Lee
MBBS, MRCOG
Department of Obstetrics and Gynaecology
Sarawak General Hospital
Editor's Notes
As women go into the menopause, the female hormones start to decline. Progesterone production is the first hormone which decreases and this can often lead to luteal insufficiency with irregular or short cycles. Thereafter, the estradiol starts to decrease. This leads to the vasomotor symptoms often experienced by women in the menopause.
This diagram shows that estrogen deficiency can lead to several symptoms and also diseases.
This diagram shows more clearly the time frame when certain climacteric symptoms and age/hormone related diseases would likely appear.
This diagram also shows the time frame when certain climacteric symptoms and age/hormone related diseases would likely appear.
2. Personal or family medical problems
a] Breast/ ovarian/ bowel cancer in close family members
in parents, sisters or brothers or the patient?
at what age did they develop it?
b] Deep vein thrombosis or pulmonary embolism
in parents, brothers or sisters or the patient
when and why: was it after a hip or knee replacement?
was the person on the “Pill” or pregnant?
did they have any test to confirm the clot?
were they treated with warfarin?
c] Risk factors for heart disease and strokes?
has the patient had a heart attack or stroke already ?
have her parents, brothers or sisters had a heart attack or stroke and if so at what age?
smoking and if so how many?
hypertension or diabetes?
high cholesterol level?
d] Risk factors for osteoporosis
was the menopause before the age of 45?
systemic corticosteroids for 6 months&apos; or more?
anorexia or significant weight loss?
family history (especially mother or sister) ?
low calcium or Vitamin D intake or deficiency, or malabsorption disorders
has the patient had a fracture already, and if so how did it happen and where was it?
e] Other
migraines, not just headaches
what medicines are being taken including herbal remedies and vitamin supplements
risk of pregnancy?
does she want to take HRT or not?
if yes, what preparation would she prefer
if not what are her most important treatment endpoints
physical examination should include BMI and BP. In March 2001, The Committee on Safety of Medicines (CSM) advised that clinical examination of the breasts and pelvic examination is not routinely necessary in all women taking HRT, but should be performed if clinically indicated. These recommendations are in line for women taking the oral contraceptive pill.
Women should also be encouraged to participate in the national cervical screening programme (cervical smear testing), which invites women aged 25-64 in England and age 20-60 in Scotland. The national mammography screening programme and breast awareness must be discussed. In the UK all women aged 50-70 years are invited to have a mammogram every 3 years. This screening is also offered to older women but currently there is no automatic invitation. In the UK, the National Institute for Clinical Excellence has produced clinical guidance for the classification and care of women at risk of familial breast cancer in primary, secondary and tertiary care.
The words &quot;clinically indicated&quot; for pelvic examination should relate to past or current disease, symptoms or family history. It is important not to miss a pelvic mass, or a pregnancy.
It is a woman&apos;s evidence based patient choice to take or not to take HRT, and her decision must be recorded in the notes.
There has been a long history of hormone replacement.
Only seven years ago, it was known that there is a small increase in breast cancer with HRT uses but overall, there was a positive risk – benefit relation because of:
efficacy in menopausal symptoms
prevention of osteoporosis and heart attacks
probably prevention of stroke and Alzheimer‘s disease
breast cancer on HRT was believed to have a better prognosis
Several studies took place.
This table compares the results from the WHI and the MWS. The results are similar for E+P but different for E alone.
The results of the WHI were perceived differently by different groups.
The patients felt that an increased risk of breast cancer was the most worry some.
The authorities and prescribers found the cardiovascular events to be more worry some.
Only seven years ago, it was known that there is a small increase in breast cancer with HRT uses but overall, there was a positive risk – benefit relation because of:
efficacy in menopausal symptoms
prevention of osteoporosis and heart attacks
probably prevention of stroke and Alzheimer‘s disease
breast cancer on HRT was believed to have a better prognosis
Only seven years ago, it was known that there is a small increase in breast cancer with HRT uses but overall, there was a positive risk – benefit relation because of:
efficacy in menopausal symptoms
prevention of osteoporosis and heart attacks
probably prevention of stroke and Alzheimer‘s disease
breast cancer on HRT was believed to have a better prognosis
Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women – principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002 Jul 17;288(3):321-33
Design: Estrogen plus progestin component of the Women&apos;s Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998.
Interventions Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102).
Conclusions: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Women’s Health Initiative Investigators.Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women&apos;s Health Initiative randomized controlled trial. JAMA. 2004 Apr 14;291(14):1701-12.
OBJECTIVE: To assess the effects on major disease incidence rates of the most commonly used postmenopausal hormone therapy in the United States. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled disease prevention trial (the estrogen-alone component of the Women&apos;s Health Initiative [WHI]) conducted in 40 US clinical centers beginning in 1993. Enrolled were 10 739 postmenopausal women, aged 50-79 years, with prior hysterectomy, including 23% of minority race/ethnicity.
INTERVENTION: Women were randomly assigned to receive either 0.625 mg/d of conjugated equine estrogen (CEE) or placebo.
CONCLUSIONS: The use of CEE increases the risk of stroke, decreases the risk of hip fracture, and does not affect CHD incidence in postmenopausal women with prior hysterectomy over an average of 6.8 years. A possible reduction in breast cancer risk requires further investigation. The burden of incident disease events was equivalent in the CEE and placebo groups, indicating no overall benefit. Thus, CEE should not be recommended for chronic disease prevention in postmenopausal women.
Beral V; Million Women Study Collaborators.
Breast cancer and hormone-replacement therapy in the Million Women Study.Lancet. 2003 Aug 9;362(9382):419-27.
BACKGROUND: Current use of hormone-replacement therapy (HRT) increases the incidence of breast cancer. The Million Women Study was set up to investigate the effects of specific types of HRT on incident and fatal breast cancer.
METHODS: 1084110 UK women aged 50-64 years were recruited into the Million Women Study between 1996 and 2001, provided information about their use of HRT and other personal details, and were followed up for cancer incidence and death.
FINDINGS: Half the women had used HRT; 9364 incident invasive breast cancers and 637 breast cancer deaths were registered after an average of 2.6 and 4.1 years of follow-up, respectively. Current users of HRT at recruitment were more likely than never users to develop breast cancer (adjusted relative risk 1.66 [95% CI 1.58-1.75], p&lt;0.0001) and die from it (1.22 [1.00-1.48], p=0.05). Past users of HRT were, however, not at an increased risk of incident or fatal disease (1.01 [0.94-1.09] and 1.05 [0.82-1.34], respectively). Incidence was significantly increased for current users of preparations containing oestrogen only (1.30 [1.21-1.40], p&lt;0.0001), oestrogen-progestagen (2.00 [1.88-2.12], p&lt;0.0001), and tibolone (1.45 [1.25-1.68], p&lt;0.0001), but the magnitude of the associated risk was substantially greater for oestrogen-progestagen than for other types of HRT (p&lt;0.0001). Results varied little between specific oestrogens and progestagens or their doses; or between continuous and sequential regimens. The relative risks were significantly increased separately for oral, transdermal, and implanted oestrogen-only formulations (1.32 [1.21-1.45]; 1.24 [1.11-1.39]; and 1.65 [1.26-2.16], respectively; all p&lt;0.0001). In current users of each type of HRT the risk of breast cancer increased with increasing total duration of use. 10 years&apos; use of HRT is estimated to result in five (95% CI 3-7) additional breast cancers per 1000 users of oestrogen-only preparations and 19 (15-23) additional cancers per 1000 users of oestrogen-progestagen combinations. Use of HRT by women aged 50-64 years in the UK over the past decade has resulted in an estimated 20000 extra breast cancers, 15000 associated with oestrogen-progestagen; the extra deaths cannot yet be reliably estimated. INTERPRETATION: Current use of HRT is associated with an increased risk of incident and fatal breast cancer; the effect is substantially greater for oestrogen-progestagen combinations than for other types of HRT.
From JAMA, 2002; 288:321-333
Data adapted from JAMA, 2002; 288:321-333
For those outcomes included in the “global index”, absolute excess risks per 10,000 person-years in the group treated with PREMPRO were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10,000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the “global index” was 19 per 10,000 person-years. There was no difference between the groups in terms of all-cause mortality.
Includes metastatic and non-metastatic breast cancer with the exception of in situ breast cancer
A subset of the events was combined in a “global index”, defined as the earliest occurrence of CHD events, invasive breast cancer, stroke, pulmonary embolism, endometrial cancer, colorectal cancer, hip fracture, or death due to other causes. DVT not included in Global Index.
In general, the increases in stroke and VTE/PE were more pronounced in the first year of treatment and are broadly in line with results anticipated from previous observational studies. It is well known that the incidence of both increase with age whether on HRT or not.
Despite over 25% of the women reporting previous use of HRT, there was little evidence of an increase in breast cancer in the HRT users under about 4-5 years of use, although breast cancer incidence was commoner in past users. However, there was no evidence of an associated increased risk with HRT use in women potentially at higher risk, e.g. a family history of breast cancer or other known “lifestyle” risks.
The increase in CHD was unexpected, but there may be an explanation for these results.
Despite the increased incidence of some conditions, there was no increase in total deaths, either from cancer or other causes.
The reductions in fractures and colo-rectal cancers were shown to increase with duration of use.
There was no evidence of an increased risk of endometrial cancer with an average 5.2 years on this ccHRT. The actual RR = 0.83, which might suggest a small but non-significant reduction.
Only seven years ago, it was known that there is a small increase in breast cancer with HRT uses but overall, there was a positive risk – benefit relation because of:
efficacy in menopausal symptoms
prevention of osteoporosis and heart attacks
probably prevention of stroke and Alzheimer‘s disease
breast cancer on HRT was believed to have a better prognosis
Only seven years ago, it was known that there is a small increase in breast cancer with HRT uses but overall, there was a positive risk – benefit relation because of:
efficacy in menopausal symptoms
prevention of osteoporosis and heart attacks
probably prevention of stroke and Alzheimer‘s disease
breast cancer on HRT was believed to have a better prognosis
Only seven years ago, it was known that there is a small increase in breast cancer with HRT uses but overall, there was a positive risk – benefit relation because of:
efficacy in menopausal symptoms
prevention of osteoporosis and heart attacks
probably prevention of stroke and Alzheimer‘s disease
breast cancer on HRT was believed to have a better prognosis
Only seven years ago, it was known that there is a small increase in breast cancer with HRT uses but overall, there was a positive risk – benefit relation because of:
efficacy in menopausal symptoms
prevention of osteoporosis and heart attacks
probably prevention of stroke and Alzheimer‘s disease
breast cancer on HRT was believed to have a better prognosis
Only seven years ago, it was known that there is a small increase in breast cancer with HRT uses but overall, there was a positive risk – benefit relation because of:
efficacy in menopausal symptoms
prevention of osteoporosis and heart attacks
probably prevention of stroke and Alzheimer‘s disease
breast cancer on HRT was believed to have a better prognosis
Only seven years ago, it was known that there is a small increase in breast cancer with HRT uses but overall, there was a positive risk – benefit relation because of:
efficacy in menopausal symptoms
prevention of osteoporosis and heart attacks
probably prevention of stroke and Alzheimer‘s disease
breast cancer on HRT was believed to have a better prognosis
The breast cancer incidence varies throughout the world.
Krieger N. Is breast cancer a disease of affluence, poverty, or both? The case of African American women. Am J Public Health. 2002 Apr;92(4):611-3.
There are several risk factors for developing breast cancer.
1.Terry PD, Miller AB, Rohan TE. Cigarette smoking and breast cancer risk: a long latency period? Int J Cancer 2002;100:723-728.
2.Easton DF. Familial risks of breast cancer. Breast Cancer Res 2002;4:179-181. Epub 2002 Aug 2.
3.Johnson KC, Wells AJ. Active and passive smoking in breast cancer. Epidemiology 2002;13:745-746.
4.Smith-Warner SA, Spiegelman D, Yaun SS, van den Brandt PA, Folsom AR, Goldbohm RA, Graham S, Holmberg L, Howe GR, Marshall JR, Miller AB, Potter JD, Speizer FE, Willett WC, Wolk A, Hunter DJ. Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA 1998;279:535-540.
5.Favero A, Parpinel M, Franceschi S. Diet and risk of breast cancer: major findings from an Italian case-control study. Biomed Pharmacother 1998;52:109-115.
6.Clavel-Chapelon F; E3N-EPIC Group. Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women. Br J Cancer 2002;86:723-727.
7.Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women – principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321-333.
8.Women’s Health Initiative Investigators. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women&apos;s Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712.
9.SEER Cancer Statistics Review 1975-2000, National Cancer Institute.
According to the WHI investigators and the estrogen alone arm, there is no good evidence of extra risk of breast cancer with estrogen alone
This diagram was taken from Clinical Gynecology Endocrinology and Infertility.
“ The doubling time of breast cancer is very variable, but in general, a tumor doubles in size every 100days. Thus, it takes a single malignant cell approximately 10 years to grow to a clinically detectable 1 cm mass, but by this time a tumor of 1cm has already progressed through 30 of the 40 doublings in size which is estimated to be associated with fatal disease. Furthermore, the average size at which a tumor is detected (70-75% of tumors are found by patients themselves) has been (prior to mammography) 2.5cm, a size which has a 505 chincidenceof lymph node involvement.”
There are 2 indications for HRT.
Estrogen deficiency symptoms in postmenopausal women (Note: the lowest effective dose for the shortest duration should be used)
Prevention of osteoporosis in postmenopausal women at high risk of future fractures who are intolerant of, or contraindicated for, other medicinal products approved for this
Women&apos;s Health Initiative Investigators.Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women&apos;s Health Initiative randomized controlled trial.JAMA. 2002 Jul 17;288(3):321-33. DESIGN: Estrogen plus progestin component of the Women&apos;s Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS: Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES: The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS: On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years.
CONCLUSIONS: Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
Therapy needs to be individualized as women differ by:
Genetics
Age and stage of menopausal (peri- or post-menopausal)
Symptoms and needs (vasomotor symptoms, urogenital atrophy, prevention of osteoporosis)
Risk factors (e.g. for breast cancer, thromboembolism)
Preferences (form of administration, withdrawal bleeds)
Habits (life style, dietary factors)
Fears