The team by mikeholy

VIEWS: 15 PAGES: 52

									       Treatment options for menopause
            symptoms after cancer
                         www.otago.ac.nz/whrc

                                                                     Oestrogen




                      Dr Beverley Lawton
                    Cancer Society June 2007

Women’s Health Research Centre             University of Otago, New Zealand
                          In a nutshell


• Information about what is
  to be expected and normal
  for menopause
• Supportive advice
• Treat if symptoms seriously
  affecting QoL
                                             Woman with fan   Amedeo Modigliani




Women’s Health Research Centre      University of Otago, New Zealand
                       Quality of Life
• Sleep deprivation

• Affects home, relationship and work

• Vaginal symptoms can be marked




Women’s Health Research Centre    University of Otago, New Zealand
    Vaginal symptoms - practical solutions

•     Have a look !
•     Get the diagnosis right
•     pH is greater than 5
•     Digital dilatation
•     Sexual activity
•     Lubricants

 NAMS, Menopause 2007 Vol 14:3

Women’s Health Research Centre   University of Otago, New Zealand
                    Vaginal treatments
• Ovestin - oestriol
• Vagifem - oestradiol vaginal tablet
• 80-90% achieve improvement in
  symptoms1
• Caution when using with Aromatase
  inhibitors2
 NAMS, Menopause 2007 14:3
 Kendall 2006 Ann Onc 17:584-587

Women’s Health Research Centre     University of Otago, New Zealand
Women’s Health Research Centre   University of Otago, New Zealand
Women’s Health Research Centre   University of Otago, New Zealand
                                 Dilators




Women’s Health Research Centre              University of Otago, New Zealand
                 Vasomotor symptoms
 • Common
 • Worse with surgical menopause.
 • Occur in 85% of women
 • Vasomotor symptoms are common reason for
   seeking medical advice1
 • For 10-20% of women these symptoms persist for
   more than 10 years2


1. Haimov-Kochman et al (2005) Acta Obstet Gynecol Scand 84 972-979
2. Position Statement, Menopause.11(1):11-33, 2004


Women’s Health Research Centre             University of Otago, New Zealand
                 Vasomotor symptoms
•   Layering clothing
•   Avoiding triggers
•   Fan
•   Open Windows




Women’s Health Research Centre   University of Otago, New Zealand
All therapeutic agents have :
• Risks
• Benefits
• Side-effects
• Interactions
Not treating:
• Opportunity Costs
• Practitioner and patient discomfort

Women’s Health Research Centre   University of Otago, New Zealand
        Thermo-regulatory agents




Women’s Health Research Centre   University of Otago, New Zealand
    Complementary and Alternative
        Medications (CAMS)




Women’s Health Research Centre   University of Otago, New Zealand
                                 CAMS
 • Surveys in USA estimate approximately
   40% of adults have used CAMS in the last
   year.
 • 43% (786 /1823) of 40-72 year olds in NZ
 • The risks and benefits of many of these
   drugs are unknown
 • Increasing focus for research as we search
   for safe alternatives to HRT

Women’s Health Research Centre          University of Otago, New Zealand
    “Natural is a marketing word”

 „Natural‟ means lack of regulation of purity,
   lack of bio-availability, efficacy and safety
                    studies…..




Women’s Health Research Centre   University of Otago, New Zealand
     Medlineplus - drugs and supplements




Women’s Health Research Centre   University of Otago, New Zealand
                                    Ginseng
Benefits
• Mental performance has been assessed using standardized measurements of reaction
   time, concentration, learning, math, and logic. Benefits have been seen both in healthy
   young people and in older ill patients.

Risks
• skin rash or spots, itching, diarrhea, sore throat, loss of appetite, excitability, anxiety,
    depression, or insomnia. Less common reported side effects include headache, fever,
    dizziness/vertigo, blood pressure abnormalities (increases or decreases), chest pain,
    difficult menstruation, heart palpitations, rapid heart rate, leg swelling, nausea/vomiting,
    or manic episodes in people with bipolar disorder.
Side-effects
• Interactionsmay reduce the anticoagulant (blood thinning) effects of warfarin Headache,
    tremors, mania, or insomnia may occur if ginseng is combined with prescription anti-
    depressant drugs called monoamine oxidase inhibitors (MAOIs ) loe vera , bilberry,
    bitter melon, burdock,fenugreek, fish oil, gymnema, horse chestnut seed extract
    (HCSE), marshmallow, maitake mushroom, milk thistle, rosemary, stinging nettle, and
    white horehound.

http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-ginseng.html


Women’s Health Research Centre                             University of Otago, New Zealand
             What does NOT work ?
• Dong quai, evening primrose oil, ginseng,
  acupuncture, magnetic therapy, melatonin,-
  no affect when compared to placebo1
• Wild yam cream1 Vitamin E 2
• Exercise - recent evidence suggests exercise
  may increase vasomotor symptoms but
  improves QoL3
  1. Position Statement, Menopause.11(1):11-33, 2004
  2. Fitzpatrick L Med Clin N Am 87 (2003)
  3. Aiello J Menopause 11(4) 2004

Women’s Health Research Centre              University of Otago, New Zealand
               No proven benefit
• Chasteberry, fish oil
• Flaxseed oil, Ginkgo
• Gotu kola, liquorice root,                   Fish oil tablets



  omega-3 fatty acids
• Passion flowers, sage,
  valerian root 1
                                                Passion flower
1. Fugate SA, Pharmacother 2004; 38: 1482-99


Women’s Health Research Centre            University of Otago, New Zealand
                      Phyto-oestrogens
• Results from RCTs in women
  have been conflicting.
• GI side-effects, Soy is
  goitrogenic1
• Possible negative effects on
  breast cell proliferation2

• Not to be recommended in breast cancer patients
1. Fugate S Ann Pharmacother 2004;38:1482-99
2. http://nccam.nih.gov/news/pastmeetings/blackcohosh_mtngsumm.pdf


 Women’s Health Research Centre             University of Otago, New Zealand
        Black Cohosh (Cimicifuga racemosa)
 • Recent trials report no benefit above
   placebo1
 • HALT trial –strong evidence black cohosh
   is ineffective for treatment vasomotor
   symptoms.5 arms BCE; BCE
   multibotanicals, BCE and soy diet advice;
   Premarin; Placebo2
1. BMJ 2006 update
2. Newton Ann Int Medicine 2006;145:869-879
Women’s Health Research Centre                University of Otago, New Zealand
                        Black Cohosh
• Safety concerns re. reports of
  fulminant hepatitis lead to NIH
  workshop in 2005
• In vivo breast data suggesting BCE
  increases the toxicity of adriamycin
  and taxotere.
• Animal models - increased
  metastatic disease in mouse                       Black cohosh flower
  mammary cancer model

http://nccam.nih.gov/news/pastmeetings/blackcohosh_mtngsumm.pdf


Women’s Health Research Centre           University of Otago, New Zealand
                Bench to the Bedside
               HOPS (Humulus lupulus)
 •     Contains a potent phytoestrogen(8-PN)
 •     Rat model using tail skin temperature (TST)
 •     8-PN injected into rats showed decreased TST1
 •     RCT over 12 weeks in 67 women showed a
       decrease in hot flush scores at 6 weeks but not
       12 weeks
 •     Safety post cancer unknown


  Bowe 2006 Soc for Endocrinology
  Heyerick 2006 Maturitas

Women’s Health Research Centre      University of Otago, New Zealand
              Prescription Medicines




Women’s Health Research Centre   University of Otago, New Zealand
                 Prescription Medicines-
                 Neuroendocrine agents
                       Antidepressants Venlafaxine,
                         Paroxetine, Fluoxetine
                       • Shown to have variable affect on
                         vasomotor symptoms. Generally fast
                         acting 1
                       • May be useful in presence of
                         depression
                       • Nine month RCT - citaloprim and
                         fluoxetine showed no effect on flushes
                         compared to Placebo 1
1. Suvanto-Luukkonen Menopause.12(1):18-26,2005

 Women’s Health Research Centre           University of Otago, New Zealand
                             Cautions
 • Small numbers, short duration of trials
 • Paroxetine inhibits cytochrome P240 (CYP2D6 )
   hence may interfere with metabolism of tamoxifen
 • Venlafaxine associated with hepatitis 1
 • Recent RCT in breast cancer patients using
   Venlafaxine looked at subjective and
   physiological measures and QoL-decreased
   flushes subjectively.2


 Phillips B Ann. (2006) Pharmacoth 40(2): 323-327
 Carpenter (2007) The Oncologist

Women’s Health Research Centre              University of Otago, New Zealand
                             Clonidine
•      Alpha adrenergic agonist
•      Improvement 27% over placebo
•      Side-effects of drowsiness, tiredness,
       constipation, dry mouth, headache,
       dizziness limits use.
•      Patch can be more useful

Grady 2006 N Engl J Med 355;22


Women’s Health Research Centre       University of Otago, New Zealand
                     Venlafaxine RCT
• Venlafaxine more effective than clonidine
• Beast cancer patients (80)
• Median reduction with venlafaxine of 7.6 hot flushes(Decr
  57%) per day vs 4.85 reduction with clonidine (decr 37%)
• Side-effects –nausea (39 %), tiredness, dry mouth and
  restless sleep
• Works within one week
• Recommended dose 37.5mg daily increasing after 1 week
  to 75mg daily

Loibl 2007 Ann.Onc 18; 689-693


Women’s Health Research Centre      University of Otago, New Zealand
                           Gabapentin
• An RCT of 59 women showed reduction of
  hot flushes by 45% compared 29%
  placebo1another as effective as oestrogen3
• Adverse effects- somnolence,
  headache,dizziness,ataxia,fatigue,
  disorientation and nystagmus (1in4)
• Safe and effective for short term use2
1. Guttuso T 2003,Obstet Gynecol 101;337-345
2. Fugate S 2004 Ann Pharmacother 38;1482-99
3. Reddy S 2006, Obstet Gynecol; 108, 1; 41-48

Women’s Health Research Centre              University of Otago, New Zealand
                         Progestagens
 • Progestagens reduce vasomotor symptoms 1
 • Safety concerns raised by WHI study.2
 • Progestagens unfavourably affect HDL
   cholesterol and fibrinogen levels 3
 • No longer use in breast cancer patients

1. Position Statement, Menopause.11(1):11-33, 2004
2. Hsia J Arch Intern Med 166, Feb 13 20061
3. Writing Group for the PEPI Trial, JAMA, 2005;273199-208

Women’s Health Research Centre               University of Otago, New Zealand
                 Progesterone Cream
•   Conflicting efficacy data
•   Variable uptake
•   No Bone protection
•   Limited endometrial safety data
•   Long term safety data needed


    Davis SR et al, J Endocrinol (2005) 185, 207-222


Women’s Health Research Centre                University of Otago, New Zealand
                         Bio-identicals
• Compounded therapies
• Often contain mixtures of powerful
  hormones for example DHEA
• Efficacy, safety and pharmaco-kinetics
  unknown1
• Calls for regulation2
  1. Climacteric 2006;9:1–3
  2. Position statement Endocrine society 2006


Women’s Health Research Centre              University of Otago, New Zealand
Women’s Health Research Centre   University of Otago, New Zealand
   Non-oestrogen dependent cancer
• Balance risks and benefits of HRT as per
  the usual menopause counselling
• QoL issues




Women’s Health Research Centre   University of Otago, New Zealand
         Common sense prescribing
• Transdermal oestrogen
• Limit progestin
• Oral micronised progesterone - Utrogeston
• ? Mirena IUCD
•  e.g Climara 50ug weekly with utrogeston
  100mg daily
• Cost barrier

Women’s Health Research Centre   University of Otago, New Zealand
             Oestrogen dependent cancer

•   Avoid oestrogen if at all possible
•   Be careful of CAMS
•   SSRI‟s –
•   Venlafaxine
•   Clonidine
•   Gabapentin
•   Oestrogen as a last resort

Women’s Health Research Centre   University of Otago, New Zealand
   Do not neglect osteoporosis risk




Women’s Health Research Centre   University of Otago, New Zealand
            Challenge for the Future
•   Further designer drugs on the horizon
•   Identify safe –effective CAMS
•   Identify safe –effective pharmaceuticals
•   Identifying safer women for safer estrogen
•   Ovarian transplant
•   Ovarian rejunevation


Women’s Health Research Centre   University of Otago, New Zealand
                    Vasomotor symptoms



                        Significant symptoms                              NO


                                  YES                     Reassurance, avoid triggers



                             Offer treatment                              NO


                                  YES


            Combined or                                 SSRIs, SNRIs
                                                   Gabapentin, clonidine
             E-only HRT

                     Discuss
Women’s Health Research Centre risks,   benefits, side effects of Otago, New Zealand
                                                     University
                        Quality of Life




Women’s Health Research Centre     University of Otago, New Zealand
                                 Kia ora
                     www.otago.ac.nz/whrc




                                 Dr Bev Lawton


Women’s Health Research Centre               University of Otago, New Zealand
                        Commonsense




Women’s Health Research Centre   University of Otago, New Zealand
        June 26, 1995




Women’s Health Research Centre   University of Otago, New Zealand
 Oestrogen – Every women's dilemma?

• Appropriate for the treatment of moderate to
  severe symptoms affecting quality of life.
• Second line therapy for the treatment of
  osteoporosis?




Women’s Health Research Centre   University of Otago, New Zealand
                            Oestrogen
• Most effective treatment
• Extensively researched
• Oestrogen alone seems to have less risk but
  is this true?
• Is transdermal oestrogen safer?
• Are we better off not using a progestogen ?


Women’s Health Research Centre      University of Otago, New Zealand
            Kia ora
           Thank you


                                 Dr Bev Lawton

                         www.otago.ac.nz/whrc
Women’s Health Research Centre               University of Otago, New Zealand
                          Thank you




Women’s Health Research Centre    University of Otago, New Zealand
             Oestrogen dependent cancer

•   Avoid oestrogen if at all possible
•   Be careful of CAMS
•   SSRI‟s – Venlafaxine
•   Clonidine
•   Gabapentin
•   Vaginal oestrogen may be considered.


Women’s Health Research Centre   University of Otago, New Zealand
          Oestrogen dependent cancer
• Use of lubricants
• Vaginal oestrogen may be appropriate but should
  be used with caution
• A small amount of oestrogen is absorbed into the
  blood.ref
• Controversy around use of topical oestrogen
  whilst on aromatase-inhibitors.
• Weigh up issues of relationship, age ,patient
  wishes


Women’s Health Research Centre   University of Otago, New Zealand
               Menopause post cancer
• Cervical cancer
• Ovarian cancer (endometroid)
• Endometrial cancer
• Radiation for other cancers –rectal for
  example
• Premature menopause


Women’s Health Research Centre   University of Otago, New Zealand
Risks
• skin rash or spots, itching, diarrhea, sore throat, loss of
   appetite, excitability, anxiety, depression, or insomnia.
   Less common reported side effects include headache,
   fever, dizziness/vertigo, blood pressure abnormalities
   (increases or decreases), chest pain, difficult menstruation,
   heart palpitations, rapid heart rate, leg swelling,
   nausea/vomiting, or manic episodes in people with bipolar
   disorder.
Side-effects
• Interactionsmay reduce the anticoagulant (blood thinning)
   effects of warfarin Headache, tremors, mania, or insomnia
   may occur if ginseng is combined with prescription anti-
   depressant drugs called monoamine oxidase inhibitors
   (MAOIs ) loe vera , bilberry, bitter melon,
   burdock,fenugreek, fish oil, gymnema, horse chestnut seed
   extract (HCSE), marshmallow, maitake mushroom, milk
   thistle, rosemary, stinging nettle, and white horehound.
Women’s Health Research Centre          University of Otago, New Zealand
          Thermo-regulatory agents
•   CAMS
•   SSRI‟s
•   SNRI‟s
•   Gabapentin
•   Clonidine
•   Progestins
•   Oestrogen

Women’s Health Research Centre   University of Otago, New Zealand

								
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