Declaration of Interest - Menopause Societymenopausesociety.be/upl_docs/en/panay.pdf · • Evidence based guidelines for diagnosis and management ... Menorrhagia 6 PMS ... Pre pubertal

Premature Ovarian InsufficiencyBelgian Menopause Society

Nick PanayChairman: British Menopause Society

Editor in Chief (Eu) Climacteric

Imperial College London

.

Declaration of Interest

Conflicts of interest

•I have lectured and acted in an advisory capacity for a number of pharma companies

•I am a patron of Daisy Network

AgendaLECTURE (1)

•Defining the POI problem

•The need for a database / registry– Principles

– Strength / Weaknesses

•Initial data from WLMC

LECTURE (2)

•Therapeutic options •Long term consequences

•Future opportunities

•Call for collaboration!

AgendaLECTURE (1)





LECTURE (2)




• Spontaneous POI estimated to affect 1% of women1

• Of increasing concern is the rising incidence of iatrogenic POI2

• Analyses from the Childhood Cancer Study3,4

• 6.3% developed acute ovarian failure • further 8% of the cohort went on to develop POI

compared to 0.8% of controls

• Risk of ovarian damage and POI high after BMT5

1Coulam CB,. Obstet Gynecol 1986 2. Panay & Fenton. Climacteric 2008 3 Chemaitilly, 2006 4 Sklar, 20065. Jadoul P Donnez J Curr Opinion 2009

• Cartwright and Islam Imperial College– Abstract ESHRE July 2011

• 1958 birth cohort studied

• 4968 participants, 370 (7.4%), had either spontaneous or medically induced POI

• Smoking/low socio economic status predictive of POI

• Poor QOL (SF 36) twice as common in POI

Premature Ovarian InsufficiencyIs the prevalence higher than previously thought?

Premature Ovarian InsufficiencyPremature Ovarian Insufficiency

• POI remains an under-researched area• Controversy over nomenclature

• ‘premature ovarian failure / dysfunction’1

• ‘primary ovarian insufficiency’2

• Lack of:• Prospective randomised controlled data• Evidence based guidelines for diagnosis and management• Standardized terminology

• Scale of the problem• Recent observational data suggested 7% incidence

(spontaneous and iatrogenic)3

• Need for high quality observational data4

1 Panay & Kalu. Bes Prac Res Obstet Gynecol, 2009 2 Welt. Clin Endocrinol, 2008 3. Cartwright & Islam Imperial College 2011 4) Panay & Fenton Climacteric 2004

AgendaLECTURE (1)





LECTURE (2)




CLIMACTERIC 2012;15:295–296

Editorial

Premature ovarian insuffi ciency: working towards an international database Nick Panay and Anna Fenton

EDITORS-IN-CHIEF

Premature ovarian insuffi ciency (POI) remains poorly under-stood and under-researched. Controversy persists over nomenclature, with terms such as ‘ premature ovarian failure/dysfunct ion’ and ‘ primary ovarian insuffi ciency’ st ill in usage. Women with POI requi re integrated care to address physical, psychosoci al and reproduct ive heal th as well as preventat ive strategies to maintain long-term health. How-ever, there i s an absence of evidence-based guideli nes for diagnosis and management.

In the absence of prospective, randomized, controlled trial (RCT) data, there is a need for high-quality observational data. There have been calls for a database/registry to provide this information 1,2 . Individual centers generally do not have suffi cient exposure to women with POI to gather suffi cient observational or RCT data to give meaningful results on dis-ease characterizat ion and long-term outcomes. Cooper and colleagues make the point that fragmented research leads to fragmented patient care 2 . We are in total agreement with Coo-per and colleagues 2 that, without defi nit ive research, we are left to advise women with POI using inappropriate postmeno-pausal pract ice guidelines that are based on a different pat ient populat ion.

The collaborat ive effort of a cohort of international centers

mechanism. The database would have the potential to defi ne and characterize the var ious presentations of POI along the lines of the STRAW 10 Guidelines for natural menopause. The STRAW 10 collaborators in their recent paper state that special groups such as POI warrant urgent attent ion for stag-ing of reproductive aging 3 . The database could also be used to further refi ne the role of biomarkers such as anti-müllerian hormone to precisely predict the course and t iming of natural and early ovarian insuffi ciency 4 .

There is a desperate need to determine long-term response to interventions such as the contraceptive pill, hormone ther-apy and those not receiving treatment. This is particularly important in women with rare causes and hormone-sensitive cancers where RCTs are unlikely ever to be performed.

Regarding treatment, quest ions which urgently need to be answered include whether the type of hormone replacement therapy (HRT) matters, body-identical versus other types of HRT, oral versus transdermal estrogen, dosage of estradiol, progesterone versus retroprogesterone versus androgenic pro-gestogens, and the impact of androgens on both short-term quality of life and long-term outcomes.

The database would also give the opportunity for the role of unproven fertility interventions in POI to be studied, such

For p

erso

nal u

se o

nly.

POI: Call for a database/registry

• “We recommend to the Department of Health that a Premature Menopause Register should be established as a

priority”

• “All those women who have undergone premature menopause and are consequently at greater risk of

osteoporosis, cardiovascular disease and cognitive decline should be on this register”

POI: Why work towards an International Database? (1)

• Rare diseases: – Limit the experience of any one centre which limits understanding of

the natural history of the disease

– Are incompletely characterised and there are few data on long term outcomes

– Induce fragmented research and fragmented patient care

• Chronic diseases such as POI require long term follow up

• RCTs are difficult in this setting

POI: Why work towards an International Database? (2)

• A woman with POI requires integrated care for her physical, psychosocial and reproductive health as well as preventative strategies to maintain her long term health

• Without definitive research we are left to advise women with POI using inappropriate postmenopausal practice guidelines that are based on a different patient population

• United, collaborative, medical research consortia can overcome these limitations

AgendaLECTURE (1)





LECTURE (2)




POI: Working towards an International Database

• The strengths of a disease database / registry– For rare / ultra rare conditions that lead to POI an international

longitudinal database may be the only feasible approach

– A database could provide the pathway to an increase in knowledgeabout the natural history of the disorder and provide the basis for assessment of long term outcomes of treatment

– It could also provide a bio-bank (clinical samples and data) with a goal of defining the specific pathogenic mechanisms involved in the development of POI e.g. unraveling the polygenic inheritance mechanism

POI: Working towards an International Database

• The potential problems of a disease database / registry– Lack of established standards of databases

– Bias or error in registry design – need a consensus on design– Quality assurance problems e.g. missing data, inaccurate data– Consistency in data collection in multiple site databases– Bias in recruitment and retention of participants– Failure to obtain a representative sample of the target population or

adequate sample size – Confusing terminology / recruitment criteria in multi-site databases

AgendaLECTURE (1)





LECTURE (2)




• Create a resource to facilitate audit, service evaluation and retrospective research

• Gather long term follow-up data from POI patients

• Aid development of evidence based treatment guidelines

Initial Database Aims

POI DatabasePOI Database

• All patients with POI entered into database

• Currently 469 from 5 years of recruitment

• Results from retrospective analysis of 450

1.Sowers et al Michigan Bone Trial JCEM 2008 2.Tehrani et al Menopause 2011 3. Broer et al JCEM 2011

Detailed history Especially for family history of early menopause

Hormone Profile FSH & LH elevated >40 on 2 occasions 4-6 weeks apartEstradiol, Thyroid function and prolactin

Autoimmune screen Anti thyroid, anti adrenal and anti ovarian antibodies

Karyotyping and genetic analysis

Karyotype / fragile X if <40yrs

Pelvic USS Ovarian Volume / Antral follicle countDEXA Baseline bone mineral densityAnti-mullerian hormone1-3

To assess ovarian reserve

“Defining Ovarian Aging and the Menopause Transition”

• 300 archival follicular phase specimens from 50 women - each woman had documented FMP

• As AMH levels declined to undetectable, this was highly associated with a time point 5yrs prior to FMP (p<0.0001)

• Baseline AMH also associated with age at FMP (p<0.035)

Sowers MR et al Michigan JCEM 2008

• Lack of standardized diagnostic criteria

• Often significant delay in diagnosiso >50% see ≥ 3 clinicians before diagnosis madeo ….in 25% diagnosis took > 5 years1

• Delay and subsequent period of estrogen deficiency cited as contributor to low bone density

1 Alzubaidi NH et al. 2002

TIME TIME TOTO DIAGNOSISDIAGNOSIS

time to definite diagnosis

0

10

20

30

40

50

60

Still un

der in

vesti

gatio

n

unde

r 6 m

onths

6 month

s to 3

years

4-7 ye

ars

more th

an 7 ye

ars

N/A had su

rgery

no. p

artic

ipan

ts

Singer et al Climacteric 2011

Aetiology

Malignant

• Haematological:

CML 22AML 16ALL 16NHL 6Hodgkins 4Myeloma 1

• Gynaecological:Cervical 26Ovarian 22Endometrial 10Vaginal 1 Choriocarcinoma 1Leiomyosarcoma 1

• Others:Breast 4Thyroid 1Sarcoma 2Bowel 2

Aetiology

Benign Genetic

• Benign gynaecological disordersEndometriosis 23Menorrhagia 6PMS 6Benign ovarian cysts 5Fibroids 1

Benign medicalβ-thalassamia major 4Sickle cell 3BRCA mutation 2 SLE 1MS 1

• Fragile X pre-mutation 3 • Testicular feminization • Mosaic 45X/46X• Turners syndrome• Ovarian dysgenesis• 17-hydoxylase/17,20-desmolase deficiency •Blepharophimosis

Aetiology

Age at Diagnosis

Average age at diagnosis: 31.6 yearsRange 11-39Genetic mean age 22.9 years

Presenting Symptoms

Symptoms by Aetiology

%**

Symptoms by age

* * p<0.05

WLMC POI Database: Key Points

• Underlying etiology can affect many aspects of POI including age at diagnosis, bone density, symptoms

• This will help us provide targeted treatment regimens and individualize management

• Ongoing follow-up of patients with POI is necessary to aid continuation of treatment…

• Management should be in specialist centres and/or with close liaison with specialist GPs/nurses

• Multi-disciplinary management

• National / International Guidelines (EMAS/IMS/ESHRE) are essential to increase knowledge and confidence in the management of POI

• Specific guidelines do not yet exist! Advances in Gynaecology, Dec 2011

Gynaecologists Affiliated specialties:Menopause Nurse Specialist FertilityPsychologist HaematologyPsychosexual counsellor Gynae oncologyDietician OncologyPharmacist

AgendaLECTURE (1)





LECTURE (2)




Principles of Hormone Replacement in POI

Estrogen replacement is first line treatment in POICommittee on Safety of Medicines www.mhra.gov.uk

1)Pre pubertal POI: To induce development of secondary sexual characteristics

2)To relieve the immediate sequelae of menopause i.e. symptom relief and quality of life

3)To prevent the long term sequelae of the menopause

4)To create an environment conducive to the successful replacement of donated embryos

Available from 15th March 2013Climacteric and Maturitas

In women with premature ovarian insufficiency, systemic MHT is recommended until the average age of

the natural menopause.

Premature Ovarian Failure

Therapeutic Options

• Route / Type HRT

• Choice of estrogen route of administration must be made on individual basis

• Recommended to continue at least until 51 years

• No controlled studies regarding the ideal hormone replacement strategy for women with premature ovarian insufficiency

In principle, non oral E2 / progesterone preparations can be better monitored but what is ideal E2 level?

Treatment

• POI typically requires higher doses of estrogen than older postmenopausal women– 75-100 µg (3-4 doses of gel) 17β-estradiol by patch

• Data are lacking regarding optimal estradiol levels for prevention of the long-term sequelae• Aim for 250 – 500pmol/l – mid follicular E2 levels

• “Body- identical” hormones typically used

HRT IN POI SHOULD BE EXEMPT FROM SCRIPT CHARGES!

• Transdermal route avoids first-pass hepatic metabolism and subsequent effects on clotting factors and SHBG – limited evidence re route - patient choice plays a crucial role!

• Progesterone in women who need endometrial protection –even after RT

• Micronised pO/pV progesterone 200mg 12 days/month • 100mg nocte continuously or Mirena (+ contraception)

• Continuous combined regimen usually 1-2 years post LMP

Timing / Use in Malignancy

• Management– Liaise with gynae oncologists / medical oncologists /

haematologists re time to start

– Immediately if curative procedure (after hist diagn)

– Delay (1 year disease free interval) if oestrogen sensitive tumour e.g. endometrial carcinoma

– HRT used in BRCA1/2 oophorectomised patients

– Treat at least until average age of menopause

– HRT “holidays” to test ovarian function

43 West London Menopause & PMS Centre

Premature Ovarian FailureTherapeutic Options

• Combined oral contraceptive pill

– “Use of ethinylestradiol has been driven by practicalities rather than science”

» Conway et al (1996)

• Often seen as simpler and more peer-friendly• But - deliver synthetic hormones in supra-physiological dose

- concerns about symptom resurgence during pill-free week

• 2 small cross-over studies HRT vs COCP– COCP most suppressed FSH1

– HRT ass/w less hyperinsulinaemia1, increased bone formation markers2 and improved lumbar spine BMD2

• RCT assessing COCP & HRT underway3

• Nuvelle vs Microgynon (and no treatment arm) over 24 months• DXA, markers of bone turnover, cardiovascular risk and ovarian

function

1 Guttman, et al. Clin Endocrinol, 2001.2 Crofton, et al. Clin Endocrinol, 2010.3 Cartwright, et al. Meno Int, 2010.

• The first estradiol COCP (Qlaira®, Bayer-Schering) • reduced hormone-free interval may prove useful• clinical trials are needed in POI

• 17β-estradiol may have favorable effects on lipid profiles and less impact on haemostasis when compared to ethinylestradiol1

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Placebo

1 2a 2b

1mg

3 4

3mg 2mg

2mg 3mg

Day

Phase

E2V

DNG

oestrogen dominant

increasing progestogenic activity oestrogen only

1 Parke S, et al. Obstet Gynecol, 2008.

• Women with POI have lower androgen levels compared to control groups (<50% after BSO)

• “Consideration should be given to androgen replacement, especially in those suffering from symptoms of testosterone deficiency, such as reduced libido or lethargy1-2”

• Aim for serum testosterone levels within physiological range to minimise side effects e.g. hair growth and acne

1.Panay et al Climacteric 20102.Maclaran/Panay Women’s Health 2011/2012

Transdermal Testosterone

2012/3Intrinsa license withdrawn by Warner Chilcott – profitability decision!

Product recently bought by HFA, marketed at £395 per month!

Androgens: Practical prescribingWhat androgens do I currently recommend?

•Testim gel / Testogel / Tostran (0.5 – 1.0ml / day)

• Unlicensed in women but data for efficacy and safety

• Pea sized blob to abdomen daily (1 week/tube or sachet)• or,1 pump every 2/3 days (Tostran)

• FAI < 6.5 (physiological female upper limit – no beards!)

•Intrinsa patches – too expensive

•Livial weakly androgenic/estrogenic enough in POI

•Testosterone implants about to be withdrawn!

Testosterone Level

1,7

5,6

7,2

0,83

5,7

3,9

2,3

3,2

0,87

3,8

0

1

2

3

4

5

6

7

8

Pretreatment 6 weeks 3months 6months 9-12 months 18-24 months

Testim&testogel Intrinsa

Alternative “HRT”

• Reducing FSH levels

• Oocyte number and quality not the only factors in subfertility of POI

• Elevated FSH levels reduce ovarian responsiveness by down regulation of the FSHr

• Suppression of FSH may increase the chances of successful OI in women with proven POI1

Optimising Fertility in POI

1. Tartagni et al Fertil Steril 2007

• Low dose body identical estradiol and natural progesterone

• 1 application E2 gel or 25mcg E2 patches

• Suppressing high FSH levels (without inhibiting possible ovulation) & improving hormonal milieu

• If some ovarian reserve - > Gentle OI with TI/IUI


Increasing DHEA levels (Controversial!)

• Role of DHEA – used to improve IVF outcome

• Egg Quality / Yield improved in poor responders though RCT not possible!

• Now case reports of spontaneous pregnancies in POI – data required!

• Micronised oral DHEA 25mg tds 3 – 6 months


Mammas & Mammas Neogenesis IVF Centre Athens Fertil Steril 2009Barad / Gleicher Center for Human Reproduction NY Fertil Steril 2009

Egg Donation

90% were nulliparous @ time of diagnosis

50% would not consider oocyte donation.

Fertility Options after POFWest London Menopause Centre

“Our donors are compassionate, caring, generous, funky, hip FABULOUS (that’s you!) young women whose acts of generosity mean more to the recipients than can ever be properly expressed in words. In a word: Thanks.”

Alarmist MediaHeadlines

Million Women Study Collaborators Lancet. 2007;369:1703-1710

Premature Ovarian FailureTherapeutic Options

• Impact of Alarmist Media on HRT use for Premature Menopause

• Ng C., Reddy N., Panay N. 2004 ESHRE Berlin

– All aware of adverse publicity

– Majority continuing with HRT BUT 37% (1/3) were contemplating stopping HRT because of breast cancer fears

– Less than half realised that risks did not apply to their age group

• Almost 7% discontinuation

• Only 1 had reached average age of menopause• 1 DVT • 1 recurrence leiomyosarcoma

• Adequate counseling re HRT vital

Advances in Gynaecology, Dec 2011

HRT ContinuationHRT Continuation

4.6%

No evidence of any increased risk of breast cancer in POIwhere the aim is to provide hormones that should be present naturally

AgendaLECTURE (1)





LECTURE (2)




Long term consequences of POI

• Few RCTs of long term consequences of POI

• Most studies are observational, mainly in women undergoing bilateral oophorectomy

• Data are of limited value – Often in women below 45yrs (not <40)

– Underlying etiology heterogeneous – different hormonal environment POI v Surgical menopause

– No long term RCTs on impact of HRT on risks

• Life expectancy• Mean life expectancy in POI 2 years less compared to women

with menopause >55 years due CV / Bone effects1

• Cardiovascular Disease• 80% increased risk of mortality from ischaemic heart disease in

POI compared to those with menopause at 49–55 years2

• Risk more pronounced in those who had never used estrogens• Danish Nurses Study – surgical menopause higher risk than POI

• Associated RFs for CVD including: » impaired endothelial function» adverse effects on the lipid profile» reduced insulin sensitivity» metabolic syndrome

*Maclaran, Horner & Panay MI 2011

1 Ossewaarde ME, et al, Epidemiology, 20052 Jacobsen Bk et al. J Clin Epidemiol ,19993 Lokkegard et al Maturitas 2006

Chu et al Human Reprod 2003

Cardiovascular disease• “Premenopausal women”

– Normally cycling premenopausal women (29-49y)

– Decreased functional ovarian reserve associated with unfavourable lipids and increased cardiovascular risk

– (D3) FSH > 7 v (D3) FSH < 7 – significantly higher lipid levels

• Chol (p < 0.001)• LDL (p< 0.019)

West London Menopause & PMS Centre,

Cardiovascular disease & HRT in POI

– Endothelial dysfunction impaired due to hypo-estrogenic state: assessed by blood flow measurements

– 6 months HRT restored endothelial dysfunction

» Kalantaridou J Clin Endoc Metab 2004

Copyright ©2004 The Endocrine Society

Kalantaridou, S. N. et al. J Clin Endocrinol Metab 2004;89:3907-3913

FIG. 1. Flow-mediated dilation (percent change in brachial artery during hand hyperemia; endothelium-dependent response) in women with POI before and after hormone therapy

and in control women

• Osteoporosis

– Women with POI have significantly lower bone density compared to controls and increased fracture risk1

– Evidence that HRT use for ≥3 years may reduce fracture risk2

1 van Der Voort, et al. Osteoporos Int 20032 van der Klift, et al. J Bone Miner Res, 2004

West London Menopause & PMS Centre,

Premature Ovarian InsufficiencyOsteoporosis

Van der Voort et al Ost Int 2003– Cross sectional population based study

– 4725 postmenopausal women in 50-70yr olds (2757 controls) filled in questionnaires

– Those with early menopause had significantly higher fracture rates OR 1.5 (CI 1.2-1.8)

West London Menopause Centre,

Premature Ovarian InsufficiencyLong term effects

• Bone Loss in young women with POI

– 45 women with POI, 61 controls

– 91% had used a variety of HRT preps

• Hip and spine DEXA significantly lower than controls (p<0.05)

Uygur et al Arch Gynecol Obstet 2005

Bone density

All Patients: 29.7 % osteopenia 5% osteoporosis

Genetic Aetiology (n=8)2 normal3 osteopenia3 osteoporosis

Longer to reach diagnosis, Less estrogen!

Limitations of bone density estimation in POI

>40% of POI patients are too young to have yet achieved their maximum bone mass

Current T and Z scores are invalid markers of bone density in POI patients

POI patients require their own group specific definitions

FRAX not applicable in women < 40

Panay et al MI

• Cognitive Impairment

– Mayo Clinic Cohort Study of Oophorectomy and Aging

– Younger than age 45 years at the time of oophorectomy

– Premenopausal oophorectomy increased risk of cognitive impairment1 and Parkinsonism2

– Risk increased with younger age at oophorectomy with protective role for estrogen replacement

– Data specific to the spontaneous POI population needed1 Rocca et al Neurology 20072 Rocca et al. Neurology, 2008 ,

Effect of POI (Surgical) on CNS• Mayo Clinic Minnesota; American Academy of Neurology

• 1209 women BSO and 1302, 1 ovary removed (1950–1987)

• RR 2.6 of Dementia following removal of at least one ovary by age 38

• RR 1.7 if both ovaries removed by age 46

• HRT was used inconsistently and probably not for long enough

Rocca et al Neurology 2007; Rocca et al Neurology 2008

• Autoimmune disorder in spontaneous POI

• hypothroidism 20%

• adrenal insufficiency 3%

• diabetes,

• myasthenia gravis,

• rheumatoid arthritis, and

• systemic lupus erythematosus

Psychological effects of POI

Psychological effects

anxiety

depression

somatisation

Self-esteem

Life satisfaction

Sexual Health Issues

Van Der Stege, Menopause 2008Schmidt, JAMA 2006Liao, Psychosom Obst Gyn 2000

Poor body-image

Psychosocial Impact of POIPsychosocial Impact of POI

–– YMA Questionnaire YMA Questionnaire – 36 questions– 220 sent out– 147 returned – 136 analysed

• 62% response rate

•• Sample:Sample:–– 2 London clinics + DN membership2 London clinics + DN membership–– Average age at diagnosis 31 Average age at diagnosis 31 –– Age range at diagnosis15Age range at diagnosis15--40 years40 years

Singer D, Mann E, Hunter M, Pitkin J, Panay N, Climacteric 2011

%

Patient concerns

Singer et al, Climacteric 2011

Psychosocial aspects of POF• Nearly all patients describe the diagnosis as traumatic, even

when sensitively handled

• Patients want more age specific information and psychological support

• 78% said POF had negative impact on self image and confidence

• Lower general health, mental well-being and sexual satisfaction than controls

Singer D, Mann E, Hunter M, Pitkin J, Panay N, Climacteric 2011

Quotes from women with POI• Aging: “I went from 36 to 56 in one day! I felt unattractive, useless,

different, an outsider”

• Fertility: “It’s the feeling of not being a proper woman… it’s the role that you should be able to choose-not have it chosen for you”

• Medical: “…from my consultant, excellent re physical issues, symptoms and treatment, but psychologically – nothing!”

• Psychosocial “…(most) people just don’t understand – support has to come from fellow sufferers”

• “Emotional issues… are forever changing. Access to regular professional support would be useful”

Editorial: Impact of POI on Sexual Function

•“Sexuality is a critical component to perceived quality of life and these women deserve our best efforts to maintain or restore sexual function.”

•“Very few studies have specifically investigated the sexual function of women with POI” (now 3!)

Kinsgberg S Menopause 2011

• Sexual dysfunction is common in POI - 32% v 19% in young controls– sexual well-being (RR 2.8), arousal, frequency1-3

– pain.

• More complex the younger the age at diagnosis

• Evidence for androgen involvement in sexual function, but…

• Serum testosterone levels may not reflect tissue androgen exposure due to the complex intracrinology of testosterone.2

Sexual dysfunction in POI

1 Van der Stege, Menopause, 2008, 2. Kalantaridou Fertil Steril 2008; 3. de Almeida et al Menopause 2011; 4. Davis SR, Menopause 2008

POI / GVHD Post BMTManagement of Sexual Pain Disorders

•Dyspareunia needs vaginal E2 +/- physiological moisturisers

•Vulvodynia – pain modulating drugs e.g. gabapentin / ganglion blocks

•GVHD / Vaginal shortening must be treated– Steroids / tacrolimus– Dilator therapy– EUA / adhesiolysis

Sturdee D, Panay N & IMS Writing Group; Climacteric; Vaginal Atrophy Recommendations 2010

Severe GVHD involving the cervix post BMT

Severe lesions involving the labia and vagina→ vaginal stenosis post BMT Agenda

LECTURE (1)


– Terminology / Nature / Scale•The need for a database / registry

– Principles



LECTURE (2)•Therapeutic options

•Long term consequences



• Create global bio bank for genetic studies / predictors of POI1

– “Unravelling the genetics of POI will need the establishment of a large international consortium”

• Characterise various presentations of POI STRAW + 10 Guidelines2

• Can we use AMH / AFC / other biomarkers to precisely predict thecourse / timing of ovarian failure?3-5

Database Opportunities (1)

1.Van Dooren MF Curr Op 2009 2.Harlow et al Climacteric 2011 3.Sowers et al Michigan Bone Trial JCEM 2008 4.Tehrani et al Menopause 2011 3. 5.Broer et al JCEM 2011

•Determine long term response to interventions e.g. COC v HRT v No treatment

– Particularly important in women with rare causes / hormone sensitive cancers where RCTs are unlikely to be performed

•Does the type of HRT matter? – Body identical E2 v Premarin – Oral v Transdermal E2– E2 / SERM– E2 dose– Progesterone / retroprogesterone v androgenic progestins

•Quantify precise risks e.g. psychological / osteoporosis /breast / cardiovascular disease / cognitive dysfunction


•Impact of Androgens – Psychosexual / Cardiovascular / Breast

•Impact of DHEA1-2 – General / Vaginal / Fertility

•Impact of ultra low dose HRT/OC on Fertility3 – does suppression of FSH levels facilitate ovulation of any remaining oocytes?


1. Mammas & Mammas Neogenesis IVF Centre Athens Fertil Steril 20092. Barad / Gleicher Center for Human Reproduction NY Fertil Steril 20093. Tartagni Fertil Steril 2007

AgendaLECTURE (1)


– Terminology / Nature / Scale•The need for a database / registry

– Principles



LECTURE (2)•Therapeutic options

•Long term consequences



Submit data to the POI registry

Submit data to the POI registryWeb based

interface

International Collaboration on POI

UK•Michael Savvas Kings Lon•Joan Pitkin London•John Stevenson, London•Farook Al Azzawi Leics•David Sturdee Bmg•Janice Rymer London•Heather Currie Scotland•Gerry Conway London•S Bhatty Aberdeen•Lynne Robinson Bmg•William Ledger Sydney exUK!

International•Rosella Nappi Italy•Andrea Genazzani Italy•Anna Fenton NZ•Rod Baber Aus•Wendy Wolfman Can•Svetlana Vuyovic Serbia•Larry Nelson USA •Serge Rosenberg Belg•Bart Fauser Ned •Valerie Baker Stanford•Barbara O’Beirne Ire

Any contributions verbally, post, e mail and offers to collaborate gratefully [email protected]; www.nickpanay.com

• Incidence of POI appears to be higher than original estimates

• Role of biomarkers in making diagnosis requires clarification and refinement

• Presentation varies depending on age and underlying etiology -knowledge of presentation and outcome will allow targeted Rx

• HRT (+/-testosterone) preferable to OC for long term hormonal support to optimise long term health– at least until average age of natural menopause (51 yrs)!

• Global database vital to collect high quality observational datauntil definitive RCT conducted

Key Take Home MessagesMany thanks to my research team!

West London Menopause and PMS Team:

Claire Bellone, Claudine Domoney, Marie Gerval, Annie Hawkins, Etienne Horner, Naomi Low-Beer, Kate Maclaran*

*POI Database: Best Free Communication @ ISGE Florence March 2012!

http://www.daisynetwork.org.uk/http://www.womens-health-concern.org/

http://www.menopausematters.co.uk/

BMS Bexley 2012

Support groups for POI

Please join the BMS!www.thebms.org.uk

2013 Annual ConferenceThursday 23/Friday 24 May 2013

Stratford-upon-Avon

Dates for your diaries

BMS Annual Scientific Meeting Stratford 23rd / 24th May 2013

BMS/RCOG ATSM Postmenopausal Health26th / 27th Nov 2013

Updated IMS Recommendations 2013: What’s Next?

1)Health Departments & Regulators – Encourage change of policy

2)The Prescribers – Expand education and training in menopause

3)Media – Engage positively highlighting favourable data

4)Pharma Industry – Reverse negative commercial/R&D decisions

5)The Menopausal Woman – Improve her access to information

6) HRT – Clarification of differences in action/risk profile

Six Action Points to Maximise Impact of Recommendations

Documents

Declaration of Interest - Menopause Societymenopausesociety.be/upl_docs/en/panay.pdf · • Evidence based guidelines for diagnosis and management ... Menorrhagia 6 PMS ... Pre pubertal