Title: Hormone Therapy
1Hormone Therapy Menopause Care
- Association of Reproductive Health Professionals
- www.arhp.org
2Expert 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
3Learning 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
4Learning 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
5Defining Menopause Perimenopause
A womans lifetime
NAMS. Menopause Curriculum Study Guide.
2002.Utian, WH. Menopause. 2001.
6Two Key Physiological Changes
Gruber CJ, et al. N Eng J Med. 2002.
7Menopause-related Symptoms
Nevin JE, Pharr ME. Prim Care. 2002.Stenchever
MA, et al. Comprehensive Gynecology, 4th ed. 2001.
8Medical Conditions More Common After Menopause
- Osteoporosis
- Atherosclerotic disease
Stenchever MA, et al. Comprehensive Gynecology,
4th ed. 2001.Wenger NK. Brit Med J. 1997.
9Fear Confusion After the WHI HERS
10Overview 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.
11Overview 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.
12Understanding WHI Results
13WHI Results CHD
Manson JE, et al. N Engl J Med. 2003. WHI
Steering Committee. JAMA. 2004. Pradham AD, et
al. JAMA. 2002.
14WHI Results Breast Cancer
Chlebowski, RT. JAMA. 2003.WHI Steering
Committee. JAMA. 2004.
15WHI Results VTE
Rossouw JE, et al. JAMA. 2002.WHI Steering
Committee. JAMA. 2004.
16WHI Results Stroke
Wassertheil-Smoller S, et al. JAMA. 2003.WHI
Steering Committee. JAMA. 2004.
17WHI Results Osteoporotic Fractures
Cauley, JA. JAMA. 2003.WHI Steering Committee.
JAMA. 2004.
18WHI Results Colorectal Cancer
Chlebowski RT, et al. N Engl J Med. 2004.WHI
Steering Committee. JAMA. 2004.
19WHI Results Quality of Life
Hays J, et al. N Engl J Med. 2003.
20WHI Results Gynecologic Cancers
Anderson GL, et al. JAMA. 2003.
21WHI Results Dementia
Rapp SR, et al. JAMA. 2003. Shumaker SA, et al.
JAMA. 2003.NIH. 2004.
22Understanding 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
23Putting 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.
24Translating Results into Clinical Practice
Oral hormone therapy post-menopausal women
25ACOG Guidelines
ACOG. 2004.
26NAMS Guidelines
North American Menopause Society. Menopause. 2003.
27NPWH Guidelines
Nurse Practitioners in Womens Health. 2004.
28FDA Guidelines
Food and Drug Administration. 2004.
29Counseling 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
30Contraindications to Systemic ET
- Pregnancy
- VTE
- Breast cancer
- Estrogen-sensitive cancers
- Liver disease
- Hypertriglyceridemia
31Weighing Risks and Benefits
32Understanding 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.
33Absolute Risk Quantified by WHI
WHI. June 2002 HRT Update. 2002.
34Absolute 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.
35Relative Risk of Breast Cancer
Collaborative Group on Hormonal Factors in Breast
Cancer. Lancet. 1997.
36Clarifying 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?
37Individualizing Hormone Therapy
- Requires
- Familiarity
- Understanding how to help a woman find the best
product and regimen
38Types of HT Estrogens
39Types 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.
40Types of HT Progestogens
NAMS. Menopause. 2003. King RJ, Whitehead MI.
Fertil Steril. 1986.PEPI Investigators. JAMA.
1995.
41Progestogens 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.
42Routes of Administration
Oral
Transdermal
Vaginal
Slater CC, et al. Menopause. 2001.
43Routes 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.
44Compounding Pharmacies
45Regimens
46Oral Therapies
47Oral Therapies
48Transdermal (Patches and Gel)
49Vaginal Creams, Tablets, and Gels
Not labeled by the FDA for menopause-related
symptoms
50Vaginal Rings and IUS
LocalSystemicIntrauterine Mirena is not
labeled by the FDA for menopause-related symptoms
Femring package insert. 2003.
51Herbal Products for Menopause Relief
Carroll DG. Am Fam Physician. 2006. Ma J,
Drieling R, Stafford RS. Menopause. 2006.
52Herbal 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.
53Androgens
- 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.
54Selective 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.
55Requirements of Individualized Care
- Gathering specific health-related information
- Providing accurate, patient-specific HT
information - Supporting informed decision making
- Addressing ongoing health needs
56Case 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
57Case 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
58Case 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
59Case 2Recommended Management
- Severe genitourinary symptoms
- No vasomotor symptoms
- Candidate for vaginal estrogen
- Could use cream, tablet, or locally acting ring
(Estring)
60Case 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
61Case 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
62Case 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
63Case 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
64Case 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
65Case 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
66Case 6 Debra R.
- 58 years old
- Has taken oral HT for 4 years
- Vasomotor symptoms and vaginal dryness have
returned over past 3 months
67Case 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
68Recommendations 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
69Summary
- 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