Hormone Therapy

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Hormone Therapy Menopause Care

• Association of Reproductive Health Professionals
• www.arhp.org

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Expert Medical Advisory Committee

• Alan Altman, MD (co-chair)
• Linda Dominguez, NP
• Karen Gunning, PharmD
• Barbara Kass-Annese, NP
• Robert Langer, MD, MPH
• Barbara Malat, CPNP, PA-C (co-chair)
• Joan Tilghman, RN, PhD
• Susan Wysocki, RNC, NP

Required Slide
3
Learning Objectives

• Identify two physiological changes associated
  with menopause
• Identify three types of symptoms women commonly
  experience during perimenopause and menopause
• Discuss key findings from the Womens Health
  Initiative (WHI) and how these findings should be
  applied to the treatment of menopausal women

more
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Learning Objectives (continued)

• Describe three effective talking points about
  menopausal therapy that help patients make
  informed decisions about hormone therapy
• Discuss four basic differences between
  prescription hormone therapies
• Discuss the current data on herbal hormone
  products
• List four requisites for individualizing hormone
  therapy

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Defining Menopause Perimenopause
A womans lifetime
NAMS. Menopause Curriculum Study Guide.
2002.Utian, WH. Menopause. 2001.
6
Two Key Physiological Changes
Gruber CJ, et al. N Eng J Med. 2002.
7
Menopause-related Symptoms
Nevin JE, Pharr ME. Prim Care. 2002.Stenchever
MA, et al. Comprehensive Gynecology, 4th ed. 2001.
8
Medical Conditions More Common After Menopause

• Osteoporosis
• Atherosclerotic disease

Stenchever MA, et al. Comprehensive Gynecology,
4th ed. 2001.Wenger NK. Brit Med J. 1997.
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Fear Confusion After the WHI HERS
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Overview of HERS

• Heart and Estrogen/progestin Replacement Study
  (HERS)
• Secondary prevention in women with CHD
• Found CEE with MPA does not reduce MIs
• More CHD events in hormone group during Year 1

Coope J. Management of the Menopause and
Post-Menopausal Years. 1976. Baumgardner SB, et
al. Obstet Gynecol. 1978. Stampfer MJ, et al. N
Engl J Med. 1985. Wilson PWF, et al. N Engl J
Med. 1985. Hulley S, et al. JAMA. 1998.
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Overview of WHI

• Womens Health Initiative (WHI )
• Primary prevention in healthy women
• Age 50-79 (mean 63 y)
• Post-menopause (mean 12 y)
• Treated with CEE with (or without) MPA
• Primary outcome rate of fatal or non-fatal MI
• E-P arm terminated July 2002
• E-only arm terminated March 2004

Rossouw JE, et al. JAMA. 2002. Anderson GL.
Press conference remarks. 2004.
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Understanding WHI Results
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WHI Results CHD
Manson JE, et al. N Engl J Med. 2003. WHI
Steering Committee. JAMA. 2004. Pradham AD, et
al. JAMA. 2002.
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WHI Results Breast Cancer
Chlebowski, RT. JAMA. 2003.WHI Steering
Committee. JAMA. 2004.
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WHI Results VTE
Rossouw JE, et al. JAMA. 2002.WHI Steering
Committee. JAMA. 2004.
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WHI Results Stroke
Wassertheil-Smoller S, et al. JAMA. 2003.WHI
Steering Committee. JAMA. 2004.
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WHI Results Osteoporotic Fractures
Cauley, JA. JAMA. 2003.WHI Steering Committee.
JAMA. 2004.
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WHI Results Colorectal Cancer
Chlebowski RT, et al. N Engl J Med. 2004.WHI
Steering Committee. JAMA. 2004.
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WHI Results Quality of Life
Hays J, et al. N Engl J Med. 2003.
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WHI Results Gynecologic Cancers
Anderson GL, et al. JAMA. 2003.
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WHI Results Dementia
Rapp SR, et al. JAMA. 2003. Shumaker SA, et al.
JAMA. 2003.NIH. 2004.
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Understanding WHI Results

• What WHI results do not tell us
• Benefits and risks of beginning HT at menopause
• Benefits and risks for treatment of
  menopause-related symptoms
• Use of other doses, formulations, regimens,
  durations, and routes of administration of HT
• Information on events after cessation

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Putting WHI Results into Context

• Well-designed study of mostly asymptomatic women
  distant from menopause
• Results have been generalized to other groups and
  to other HT formulations
• Not yet known if findings apply

Lobo RA. Arch Intern Med. 2004.
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Translating Results into Clinical Practice
Oral hormone therapy post-menopausal women
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ACOG Guidelines
ACOG. 2004.
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NAMS Guidelines
North American Menopause Society. Menopause. 2003.
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NPWH Guidelines
Nurse Practitioners in Womens Health. 2004.
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FDA Guidelines
Food and Drug Administration. 2004.
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Counseling Patients About HT

• Each woman must weigh risks and benefits in light
  of her circumstances
• Women must put risks into perspective to make
  fully informed decision
• Each woman must clarify her purpose and goal for
  using HT

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Contraindications to Systemic ET

• Pregnancy
• VTE
• Breast cancer
• Estrogen-sensitive cancers
• Liver disease
• Hypertriglyceridemia

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Weighing Risks and Benefits
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Understanding Risk

• WHI 26 increase in breast cancer in E-P arm
• This does not mean 26 chance of getting breast
  cancer

International Food Information Council. 2004.
Nurse Practitioners in Womens Health. 2004.
Rossouw JE, et al. JAMA. 2002.
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Absolute Risk Quantified by WHI
WHI. June 2002 HRT Update. 2002.
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Absolute Risk Quantified by WHI
Huang Z. JAMA. 1997. LaCroix AZ. Lancet.
1997. Longnecker MP. Cancer Epidemiol Biomarkers
Prev. 1995. Smith-Warner SA. JAMA. 1998. Thune
I. N Engl J Med. 1997. WHI. 2002.
35
Relative Risk of Breast Cancer
Collaborative Group on Hormonal Factors in Breast
Cancer. Lancet. 1997.
36
Clarifying Goals or Purpose

• Risk/benefit ratio varies based on goals

What is most important among your
menopause-related health concerns?
Why do you want to start/continue HT?
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Individualizing Hormone Therapy

• Requires
• Familiarity
• Understanding how to help a woman find the best
  product and regimen

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Types of HT Estrogens
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Types of HT Progestogens
Adams MR, et al. Arteriosclerosis. 1990. Adams
MR, et al. Arterioscler Thromb Vasc Biol. 1997.
Espeland MA, et al. J Clin Endocrinol Metab.
1997. NAMS. 2002. Williams JK, et al. J Am
Coll Cardiol. 1994.
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Types of HT Progestogens
NAMS. Menopause. 2003. King RJ, Whitehead MI.
Fertil Steril. 1986.PEPI Investigators. JAMA.
1995.
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Progestogens Possible Side Effects

• Swelling and breast pain more common with MPA
• Acne and hirsutism more common with
  levonorgestrel and norethinedrone
• Dizziness and fatigue associated with high-dose
  progesterone
• Metabolic effects differ

NAMS. Menopause. 2003. Mitchell JL, et al. Prim
Care. 2003.PEPI Investigators. JAMA. 1995.
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Routes of Administration
Oral
Transdermal
Vaginal
Slater CC, et al. Menopause. 2001.
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Routes of Administration Differences

• Systemic vs. local effects
• Even vs. uneven blood levels
• First-pass metabolism or not
• Hemostatic effects or not
• Risk of VTE
• Effects on procoagulants and lipids
• Need for concomitant progestogen

Vongpatanasin W. J Am Coll Cardiol. 2003.
Decensi A. Circulation. 2002. Scarabin PY.
Lancet. 2003. Femring package insert. 2003.
Hemelaar M. Menopause. 2003.
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Compounding Pharmacies
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Regimens
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Oral Therapies
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Oral Therapies
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Transdermal (Patches and Gel)
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Vaginal Creams, Tablets, and Gels
Not labeled by the FDA for menopause-related
symptoms
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Vaginal Rings and IUS
LocalSystemicIntrauterine Mirena is not
labeled by the FDA for menopause-related symptoms
Femring package insert. 2003.
51
Herbal Products for Menopause Relief
Carroll DG. Am Fam Physician. 2006. Ma J,
Drieling R, Stafford RS. Menopause. 2006.
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Herbal Products Do They Work?

• Black cohosh
• Red clover
• Dong quai
• Soy
• Evening primrose seed oil

Carroll DG. Am Fam Physician. 2006. Low Dog T.
Am J Med. 2005. NIH/NCAM. 2005. Newton KM, et
al. Ann Intern Med. 2006. Pockaj BA, et al. J
Clin Oncol. 2006.
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Androgens

• Estratest and Estratest HS indicated for
  vasomotor symptoms if estrogen alone ineffective
• Testosterone has also been used to improve sexual
  function
• Not FDA-approved for this use

OBGYN.net. 2003. Estratest and Estratest HS
package insert. 2004.
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Selective Estrogen Receptor Modulators

• Mediate effects through estrogen receptor binding
• Activate certain estrogenic pathways and block
  others
• Not indicated for menopause-related symptoms
• Can cause hot flashes from estrogen receptor
  blockade

Evista package insert. 2001.
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Requirements of Individualized Care

• Gathering specific health-related information
• Providing accurate, patient-specific HT
  information
• Supporting informed decision making
• Addressing ongoing health needs

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Case 1 Mary S.

• Final menstrual period 18 months ago at age 49
• Healthy with no CHD risk factors
• Hot flashes daily
• Herbal remedies not helping
• Terrified of those hormone drugs

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Case 1Recommended Management

• Symptomatic with no contraindication
• Candidate for systemic HT, not local HT
• To decide on route, consider her preference,
  medical history, other factors
• Progestogen needed if oral, transdermal, or
  systemic vaginal therapy is chosen

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Case 2 Zelda K.

• 60 years old
• 8 years postmenopausal
• Has never taken HT
• Severe dyspareunia, urinary urgency, and
  frequency X 1 year
• Does not want oral HT, because friend had DVT on
  it

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Case 2Recommended Management

• Severe genitourinary symptoms
• No vasomotor symptoms
• Candidate for vaginal estrogen
• Could use cream, tablet, or locally acting ring
  (Estring)

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Case 3 Ann P.

• 56 years old
• Was taking oral HT for
  vasomotor symptoms
• Internist told her to stop HT
• Off HT several months
• Vasomotor symptoms
  gone but sexual desire low
• Wants to restart HT
• No contraindications to systemic HT

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Case 3Recommended Management

• Provider should ask about sexual function,
  relationship, and pharmacological issues to
  clarify cause
• Low sexual desire may be related to low hormone
  levels
• May be candidate for restarting HT, possibly with
  androgen

62
Case 4 Terri O.

• 48 years old
• Perimenopausal
• Menses generally regular
• Experiencing hot flashes, mood swings, and
  fatigue
• Requests HT
• Had DVT on oral contraceptive at age 35
• No other medical problems

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Case 4Recommended Management

• HT should not be used during perimenopause

• OCs contraindicated
• Could use estrogen augmentation with patch
• Does not need progestogen menses still regular
• Needs progestogen challenge if no menses X 3
  months
• Before any form of HT is started, possibility of
  pregnancy should be investigated, as appropriate

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Case 5 Katherine W.

• 54 years old
• Post hysterectomy
  without oophorectomy
• Recent severe vasomotor
  symptoms and forgetfulness
• Afraid of HT
• Family physician told her recent
  studies showed HT causes breast cancer
• Healthy, no contraindications to HT

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Case 5Recommended Management

• Candidate for oral or non-oral
  systemic HT
• Does not need progestogen
• Provider should educate about actual risks
  associated with HT
• HT could be used for a short time, then gradually
  reduced to avoid estrogen withdrawal symptoms

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Case 6 Debra R.

• 58 years old
• Has taken oral HT for 4 years
• Vasomotor symptoms and vaginal dryness have
  returned over past 3 months

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Case 6Recommended Management

• If adherence not an issue, relapse likely because
  of increased SHBG caused by oral estrogen
• Options include adding androgen or changing to
  non-oral estrogen

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Recommendations for Further Study

• HT using other routes of administration, hormone
  components, and regimens
• Comparison of bio-identical products
• Use of androgens alone or with HT
• Factors that affect patient adherence
• How patients make decisions about HT
• Optimal regimens for discontinuing HT

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Summary

• Patients and providers have been confused about
  HT as a result of the WHI and HERS data
• Understanding study results and limitations helps
  providers counsel women to make informed
  decisions about HT
• Individualization of therapy is essential for
  women who decide to use HT