Hormone Therapy HT

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Hormone Therapy (HT)
Tom LeBlanc, MSII September 25, 2003
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Terminology

• Also known as Hormone Replacement Therapy
  (HRT), or Ovarian Hormone Therapy
• Hormone Replacement Therapy indicates that
  hormones that should be there are not there in
  postmenopausal women. This is contrary to the
  facts, and is, furthermore, a term that implies
  there is something wrong with the normal hormonal
  status of all menopausal and postmenopausal
  women. the Society for Menstrual Cycle Research

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Terminology

• Furthermore, the usage of terms like HRT
  contributes to the medicalization of normalcy,
  turning a common transition into pathology
• Thus the FDA recently adopted the term
  menopausal hormone therapy to replace HRT
• When estrogen alone is used, you may also hear it
  referred to as Estrogen Replacement Therapy
  (ERT)

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A Little About Menopause

• Menopause actually refers to the final
  cessation of menstruation
• On average, occurs at 51 years of age in Western
  societies
• A process, which can begin years before ones
  final menstrual period
• Menstrual cycles become more irregular more
  anovulatory cycles, fewer cycles/yr, etc.
• Flow decreases due to lower estrogen levels

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Common Findings

• Menopausal Signs and Symptoms
• hot flashes / hot flushes
• night sweats
• vaginal dryness / urogenital atrophy
• mood changes / irritability
• depression
• Also insomnia! (VERY often overlooked)
• If you arent thinking about it, youll miss it
• Can present perimenopausal, and worsen
• Severity varies IMMENSELY!

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What IS a Hot Flash?

• Feeling of intense heat over the trunk and face,
  with skin flushing and sweating
• May begin before menses cease permanently
• Thought to result from increasing pulsatile
  release of GnRH from the hypothalamus, thereby
  affecting the nearby temperature-regulating area
  in the brain
• More pronounced late in the day, during hot
  weather, periods of tension, or after ingesting
  hot foods/drinks

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Diagnosis

• Based on the presence of symptoms
• Elevation of serum FSH and LH levels
• Diagnosis solidified once bleeding has ceased for
  one year
• Indeed, if bleeding occurs after this time, it
  should be investigated to rule out endometrial CA
  (by biopsy)

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Why Give Hormones?

• Symptomatic relief (most common usage)
• Decreased estrogen leads to
• increased bone resorption ? Osteoporosis
• Increased risk of cardiovascular disease (?)
• Increased risk of colon cancer
• Estrogens affect a plethora of other tissues and
  systems, including the skin, brain, eyes, teeth,
  heart, breast, UG tract, and vasomotor system.

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Benefits Colon Cancer

• A 2002 meta-analysis demonstrates a 20 reduction
  in colon cancer and a 19 reduction in rectal
  cancer in women who had ever used postmenopausal
  HT compared with never users.
• The observed decrease was greatest among current
  users, with 34 risk reduction.
• The duration of therapy had no effect on cancer
  risk.

Jagadeesan, Udaya B. An Incentive to Start
Hormone Replacement The Effect of Postmenopausal
Hormone Replacement Therapy on the Risk of
Colorectal Cancer. Journal of the American
Geriatrics Society  50 (4), 768-770, 2002.
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Benefits Alzheimers

• Estrogen has a reported neuroprotective effect
• Studies of cognitive function in individuals have
  established that, during memory processing,
  estrogen increases glucose transport and regional
  cerebral blood flow, which are decreased in
  Alzheimers.
• ERT/HT users exhibited enhanced regional cerebral
  blood flow in the hippocampus, the
  parahippocampal gyrus, and the temporal lobe,
  regions fundamental to memory function that can
  reveal preclinical abnormalities in individuals
  at risk for Alzheimers Disease.
• However, clinical evidence remains inadequate.

Fillit, Howard M. The Role of Hormone
Replacement Therapy in the Prevention of
Alzheimers Disease. JAMA, v. 162, no. 7, Sep.
23, 2002.
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Benefits Fractures

• JAMA 2002, 288321-33. Womens Health
  Initiative (WHI) investigators found a 34
  decrease in hip fractures in postmenopausal women
  taking estrogen and progestin
• Estrogens prevent/slow bone resorption in
  menopausal women
• Bone demineralization occurs earlier in life than
  you might think!

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Benefit? Cardiovascular Disease

• Generally, estrogens lower LDL, raise HDL, and
  increase triglycerides
• However, the WHI study demonstrated a significant
  increase in cardiovascular disease
• 29 increase in MI
• 41 increase in stroke
• (after 5.2 yrs of estrogen progestin use)

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The WHI Study
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The WHI Study
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The WHI Study
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The WHI Study
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Estrogen and memory?

• It is thought that estrogens play an important
  role in cognition and memory!

Miller, Karen J. Mood Symptoms and Cognitive
Performance in Women Estrogen Users and Nonusers
and Men, J. Amer. Ger. Soc., Nov 2002.
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Estrogens and Cognition
Attention and working memory
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Estrogens and Mood
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Estrogens in Mood and Cognition

• Female ERT users were less depressed and less
  angry and performed better on measures of verbal
  fluency and working memory than the other subject
  groups.

Miller, Karen J. Mood Symptoms and Cognitive
Performance in Women Estrogen Users and Nonusers
and Men, J. Amer. Ger. Soc., Nov 2002.
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Breast Cancer and HT

• There continues to be much debate about the
  potential link between estrogen replacement and
  breast cancer
• One of the more respected meta-analyses says,
  The risk of having breast cancer diagnosed is
  increased in women using HRT and increases with
  increasing duration of use. This effect is
  reduced after cessation of use of HRT and has
  largely, if not wholly, disappeared after about 5
  years. These findings should be considered in the
  context of the benefits and other risks
  associated with the use of HRT.

Santen, Richard J. Relative Versus Attributable
Risk of Breast Cancer from Estrogen Replacement
Therapy. Journal of Clin Endocrin Metabol, v.
84, no. 6, 1875-81, 1999.
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Why NOT replace?

• Surveys indicate only about 20 of US
  postmenopausal women are on HT! Why?
• Risks
• Breast Cancer?
• Endometrial Cancer (if unopposed)
• Thromboembolism
• Triglyceride elevation
• Gallbladder disease
• Migraines
• Ovarian Cancer?

Santen, Richard J. Relative Versus Attributable
Risk of Breast Cancer from Estrogen Replacement
Therapy. Journal of Clin Endocrin Metabol, v.
84, no. 6, 1875-81, 1999.
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Side Effects

• For many women, HT causes significant side
  effects
• Bleeding
• Bloating
• Breast Tenderness or Enlargement
• Headaches
• Mood Changes
• Nausea

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Alternatives to HT

• Osteoporosis
• bisphosphonates, weight-bearing activity,
  calcitonin nasal sprays, raloxifene (Evista, a
  SERM)
• Heart Disease
• lifestyle modification (diet, exercise),
  medication (statins)
• Hot Flashes
• stress reduction, avoidance of spicy foods and
  caffeine, eating soy (contain phytoestrogens),
  other sources of phytoestrogens (black cohosh)
• Vitamin E, or Clonidine

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Alternatives (cont.)

• Vaginal Dryness
• local estrogen creams, lubricants, etc.
• Insomnia
• OTC sleep aids, milk products, physical activity
  in morning/afternoon only
• Memory
• mental exercises, physical activity, more sleep

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The Choice Remains Unclear

• HT is not the only way to relieve the symptoms of
  menopause
• The risks of HT may in some cases outweigh the
  benefits
• Alternative therapies are the rage, but may carry
  similar risks in that they contain phytoestrogens
• Everyone is different (risk profiles, response,
  etc.)

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Life Expectancy
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SERMs The New Frontier

• Estrogen receptors in a HUGE range of tissues
  (high amount in unexpected ones, like kidney!)
• Each tissue responds in a unique way to each
  unique estrogen
• So the idea is that you can design specific
  estrogens for specific purposes
• Example Raloxifene (Evista) for osteoporosis

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Treatment Regimens

• Oral conjugated estrogens (0.3 or 0.625mg),
  estradiol (0.5 or 1mg), or estrone sulfate,
  0.625mg
• Unless hysterectomy, add a progestin, like
  Provera (medroxyprogesterone acetate)
• Cyclic regimen estrogen on days 1-25, with
  5-10mg of Provera on days 14-25, then withhold
  hormones on days 26 to the end of the month
• Note this will cause a light, generally painless
  period

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Treatment Regimens

• Continuous regimen estrogen, along with 2.5mg of
  Provera every day, without stopping
• Alternatives Estrogen patch, Vaginal ring,
  creams, gels, etc.
• When stopping therapy, its very important to
  taper doses to minimize the return of hot
  flashes, etc.

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So, Should Everyone be on HT?

• Individual decision, based on symptom severity,
  perceived risks vs. benefits, etc.
• For a patient at high risk for osteoporosis, with
  severe menopausal symptoms, and a high risk for
  cardiovascular disease, yes!
• For the asymptomatic patient with a significant
  family history of breast cancer, no way!
• But what about those in between people???
• We need more data!

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References

• Fillit, Howard M. The Role of Hormone
  Replacement Therapy in the Prevention of
  Alzheimers Disease. JAMA, v. 162, no. 7, Sep.
  23, 2002.
• Miller, Karen J. Mood Symptoms and Cognitive
  Performance in Women Users and Nonusers and Men.
  Journal Amer. Ger. Soc. Volume 50 Issue
  11 Page 1826  - November 2002
• Miller, Karen J., Conney, Janet C., Rasgon,
  Natalie L., Fairbanks, Lynn A. Small, Gary W.
  (2002)Mood Symptoms and Cognitive Performance in
  Women Estrogen Users and Nonusers and
  Men.Journal of the American Geriatrics Society 
  50 (11), 1826-1830.
• Jagadeesan, Udaya B. (2002)An Incentive to Start
  Hormone Replacement The Effect of Postmenopausal
  Hormone Replacement Therapy on the Risk of
  Colorectal Cancer. Journal of the American
  Geriatrics Society  50 (4), 768-770.
• Kamel, Hosam K., Perry, Horace M. Morley, John
  E. (2001)Hormone Replacement Therapy and
  Fractures in Older Adults.Journal of the
  American Geriatrics Society  49 (2), 179-187.
• Padero, Ma Clara M., Bhasin, Shalender
  Friedman, Theodore C. (2002)Androgen
  Supplementation in Older Women Too Much Hype,
  Not Enough Data.Journal of the American
  Geriatrics Society  50 (6), 1131-1140.
• Santen, Richard J. Relative Versus Attributable
  Risk of Breast Cancer from Estrogen Replacement
  Therapy. Journal of Clin Endocrin Metabol, v.
  84, no. 6, 1875-81, 1999.
• Tierney, Lawrence M. Current Medical Diagnosis
  and Treatment. New York McGraw-Hill, 2003.