The Individualized Approach to Menopause Management

1
The Individualized Approach to Menopause
Management

• JCEM 1999 Vol. 84, No. 6 1900-1904

2
Case 1 I cant stand this bleeding any more!

• Solving bleeding problems

3
History

• 54-yr-old women
• last menses at age 49 having some hot flashes
  and sleep disturbance
• smoking 1-pack-per-day for 35 yrs
• BMD 1.9 SD
• request HRT to prevent osteoporosis
• High 160 cm BW 76.3 KgW mild obesity

4
Treatment and Course

• No contraindications normal mammogram
• stop smoking
• 0.625 mg conjugated equine estrogens with 2.5 mg
  medroxyprogesterone acetate daily
• One month later
• cause bleeding light but nearly continuous
• verify she hasnt missed any pill
• reassure common and short-lived
• Three months of treatment
• bleeding is less often, but still bothersome
• increase progestin to 5 mg daily

5

• Six months of treatment
• still complaining of the bleeding
• ultrasound thin endometrial stripe, 3.2 mm
• lower estrogen dose to 0.3 mg daily
• Three months later
• bleed for only a few days per month, but still
  unacceptable
• discuss cyclic hormonal treatment, other drugs
  -- such as raloxifene and alendronate

6
1. Set realistic expectations from the start

• The vast majority of patients who have a uterus
  will bleed when they begin taking continuous
  combined hormone replacement.
• 60 will experience some amount of bleeding even
  after 6 months of treatment

7
2. Avoid situations where continuous combined HRT
is likely to fail

• More likely to have breakthrough bleeding
• overweight, recently postmenopausal, history of
  menorrhagia (esp. due to submucous fibroids)
• Thin women without submucous fibroids who are
  several years beyond the menopause --- best
  candidates for continuous HRT

8
3. Try increasing the progestin dose

• Progestins oppose the proliferative effects of
  estrogen on the endometrium.
• 60 will bleed after 6 months of 2.5 mg
  medroxyprogesterone daily
• 47 will bleed when given 5 mg daily
• side effect bloating, fluid retention, breast
  tenderness and mood swings

9
4. Rule out structural abnormalities of the
uterus the role of biopsy, ultrasound,
hysteroscopy

• First, try to improve the bleeding by adjusting
  the dose of hormones.
• If it fails, look for the etiology of this
  bleeding
• transvaginal ultrasound thickened endometrium ?
  5 mm ? biopsy if inconclusive ? hysteroscopy to
  identify endometrial polyps and submucous
  fibroids
• Bleeding that occurs years after achieving
  amenorrhea is particularly worrisome ? biopsy

10
5. Try lowering the estrogen dose

• Until recently, 0.625 mg conjugated estrogen
  daily was considered to be the minimum effective
  dose of estrogen
• A recent study that a lower dose, 0.3 mg daily,
  may be effective in preventing osteoporosis.
• Some patients may experience a return of hot
  flashes when the estrogen dose is lowered.

11
6. Switch to a cyclic regimen

• is preferable to erratic bleeding

7. Reassess the need for HRT, and perhaps switch
to a nonestrogen treatment

• Selective estrogen receptor modulator (SERM) or
  bisphosphonate

12
Case 2 I dont want to get severe osteoporosis
like my mom did, but Im scared that estrogen
will give me breast cancer.

• Responding to the fear of breast cancer

13
History

• 56-yr-old women
• last menses at age 53
• FH mother with hip fracture at age 69 and died
  2 months (unclear reason), her mother lose 7.5 cm
  several yrs before hip FxHer paternal aunt died
  of breast cancer
• Her BMD hip and spine, T-score of 1.6

14
Treatment and Course

• No contraindication normal PE and mammogram
• reassure the benefits exceed risk
• prescribe continuous HRT
• One year later
• BMD T-score of 1.9
• never fill her prescription
• consider raloxifene and alendronate

15
1. Acknowledge that fear of breast cancer is a
major barrier of HRT use and is a common reason
for discontinuation

• Most of patients are unaware that cardiovascular
  disease is the leading cause of death of
  postmenopausal women in industrialized countries
• 4 due to breast cancer
• less than 45 due to cardiovascular disease
• 1995 Gallup survey
• 40 of women identified breast cancer as the
  leading cause of death 19 identify heart
  disease

16
2. Understand that the risk of breast cancer is
probably increased to a small degree with
long-term (i.e.more than 5-10 yr) postmenopausal
estrogen use

• No significant evidence indicating that duration
  less than 5 yr will increase the risk of breast
  cancer
• For duration of greater than 5-10 yr, most but
  not all studies probably on the order of 2
  excess risk per year of estrogen treatment

17
3. Most women who develop breast cancer do not
have a family history

• Over 80 of women diagnosed with breast cancer
  do not have a family history

18
4. Consider alternatives to estrogen treatment
that could satisfy the patients needs

• Raloxifene increases bone density without
  stimulating the endometrium
• lower the risk of breast cancer by more than 50
  ( in placebo-controlled clinical trial )
• Raloxifene may also be cardioprotective
• lower LDL-C, fibrinogen and lipoprotein(a),
  without increasing TG

19
Case 3 The estrogen makes me feel so much
better but I HATE my progestin!

• Alternatives to the standard progestin

20
History

• W.E. is a 49-yr-old woman whose last menses were
  7 months ago. She describes herself as not a
  pill-taker and had planned to breeze though the
  menopause using relaxation techniques and
  exercise. Her hot flashes began 3 yr ago and,
  much to her surprise, were more severe than she
  expected. In fact, they have not gotten any
  better over these past 3 yr. At this point she is
  desperate for a good nights sleep. She requests
  estrogen treatment.

21
Treatment and Course

• No contraindication normal PE and mammogram
• prescribe 0.625 mg of conjugated equine estrogens
  daily, with 5 mg medroxyprogesterone acetate on
  days 1 to 14
• One month later
• she feels like a new person less hot flashes
  improved sleep quality

22

• Four months later
• she reports that she feels wonderful when she
  takes just the estrogen, but has mood swings,
  depression, and breast tenderness when she adds
  on the progestin
• her monthly withdrawal bleeding is light and is
  appropriately timed on days 11 to 14
• take medroxyprogesterone every other month

23

• Two months later
• report her withdrawal bleeding was quite heavy
  after taking medroxyprogesterone mood swings
  were intolerable
• try megestrol acetate 40 mg, micronized
  progesterone 100 mg, and norethindrone acetate
  0.70 mg as alternative progestins
• basically the same as medroxyprogesterone
• vaginal progesterone -- she declines as it sounds
  messy and stop estrogen
• resume estrogen without progestins because hot
  flashes recur with a vengeance

24

• Risk of endometrial cancer
• lower estrogen to 0.3 mg daily and perform annual
  endometrial biopsy
• she is comfortable with this plan
• 4 years latter, she discontinues her estrogen and
  no symptoms thereafter

25
1. Try lowering the dose or the frequency of the
progestin

• In the past
• Provera 10 mg for cyclic treatment and 5 mg for
  continuous treatment
• Half of doses have been found to protect the
  endometrium equally well and are more typically
  used today
• If patients have problems with the lower doses
  --- try taking progestin every other or even
  every third month
• may not be well protected against endometrial
  cancer and need F/U by annual ultrasound or by
  biopsy

26
2. Switch to another progestin altogether, such
as megestrol acetate 40 mg daily, micronized
progesterone 100 mg daily, norethindrone acetate
0.7 mg daily, or 4 vaginal progesterone gel
every other day

• Many women will have far few side-effects with a
  different progestin
• idiosyncratic --- it cannot be predicted
• vaginal gel --- lower systemic effects

27
3. Use unopposed estrogen, especially at a lower
dose and monitor carefully

• Absolute risk approximately 2-4 women per
  thousand per year
• lower the estrogen dose to the lowest level, that
  may minimize risk

28
4. Reassess the need for HRT, and perhaps switch
to a nonestrogen treatment

• Against osteoporosis SERM, bisphosphonate
• Cardioprotection diet, exercise, statin
• urogenital atrophy intravaginal estrogen cream
  or estradiol-impregnated silicone vaginal ring

29
Case 4 Even since the menopause, I just dont
feel the same even when I take estrogen

• An approach to atypical symptoms

30
History

• 47-yr-old women seeks a second opinion regarding
  hormone management
• PH total abdominal hysterectomy with bilateral
  salpingoophorectomy 2 yr ago (chronic pelvic
  pain)
• does not like herself cry easily poor sleep
  no clear-cut hot flashes body weight gain 6.8
  kgw
• has seen 3 other gynecologists
• have prescribed several different estrogens with
  any improvement in her sense of well-being
• reject depression
• perfectly fine before hysterectomy

31
Treatment and Course

• Sad affect and weep easily normal mammogram
• prescribe 100 ug transdermal estradiol twice
  weekly
• 6 weeks later
• no difference
• prescribe 0.625 mg conjugated estrogen with 2.5
  mg methyltestosterone daily
• 2 months later
• would like to take a higher dose of these
  hormones
• prescribe 1.25 mg conjugated estrogen with 5 mg
  methyltestosterone daily

32

• One month later
• feeling 50 improved
• Two months later
• backslid totally and feels even worse
• a trial of a SSRI fluoxetine 20 mg daily for 4
  week
• one moth later --- significant improvement

33
1. Not all women experience menopause in the same
way --- even unusual symptoms can be caused by
estrogen withdrawal

• Try to reserve judgement
• If a symptom interferes with a patients quality
  of life --- giving a diagnostic test of
  estrogen
• resolve with 1-2 months of estrogen treatment ---
  presumably related to the menopause

34
2. Not all symptoms experienced by women in their
50s are due to estrogen withdrawal

• Before prescribing hormones for an impaired sense
  of well-being, it is worthwhile to inquire about
  other issues that may be troubling the patient

35
3. Prescribe a diagnostic test of unopposed
estrogen for 1-2 months

• A transdermal estrogen patch can act like an
  artificial ovary --- this one mimics the
  premenopausal state the most avoid peaks and
  valleys
• oral estrogen
• largely convert to estrone, a weaker estrogen, by
  intestinal mucosa ? high concentration in liver ?
  pharmacological effect on hepatic metabolism

36
4. Consider a diagnostic test of a low dose of
testosterone for 2 months

• Serum testosterone levels are reduced by
  oophorectomy
• testosterone supplement lower
  sex-hormone-binding globulin level --- increase
  free estrogen and testosterone
• measurement of testosterone levels is usually not
  informative
• lack sensitivity not significantly detect
  methyltestosterone individual variation in
  response to a given level
• best followed by clinical response rather than T
  level

37
5. Make only on change at a time in your medical
management so that you know what change to blame
or to give credit
6. Add a progestin only after you have
established that the estrogen is effective in
symptom relief

• Many women report impaired sense of well-being
  with progestins
• identify if estrogen and /or androgen improves a
  patients sense of well-being before adding
  progestin
• little risk in prescribing unopposed estrogen for
  less than 1 yr

38
7. Consider depression and a trial of selective
serotonin-reuptake inhibitor (SSRI)

• Many women with chronic pelvic pain are not cured
  by hysterectomy, as the pain stems from
  depression, not from intrinsic pelvic pathology.
• Explain low serotonin levels in their brain

39
Case 5 My doctor insists that I cant be
having hot flashes because Im still having
periods. He did a blood test that showed that I
cant be menopausal

• Responding to the perimenopausal patient

40
History

• J.K. is a 48-yr-old women who presents with
  night sweats for the past 6 months ---
  typically will be awakened 3-4 times each night,
  feeling a hot sensation that originates in her
  chest and rises to her face
• After a few minutes, she experiences a drenching
  sweat that requires her to change her nightgown.
• She is thoroughly exhausted
• regular menses every 25-29 days on occasion may
  be delayed by an additional few days
• she is sexually active and uses the diaphragm
• she is a nonsmoker
• Internist found her to be in good health TSH 2
  mIU/L FSH 8 mIU/mL

41
Treatment and Course

• No contraindications to oral contraceptive
  normal PE and mammogram
• prescribe a low-dose oral contraceptive
  containing 20 ug ethinyl estradiol
• 3 months later
• hot flashes are gone, improved sleep
• light withdrawal bleeding during placebo week
• no longer need to use diaphragm
• annual F/U for 4 yrs
• switch to continuous HRT
• 3 months later
• persistent breakthrough bleeding
• switch to cyclic HRT timed and light bleeding

42
1. The most severe and frequent hot flashes occur
2-3 yr before the final menses

• Hot flashes are not caused by low estrogen levels
  per se, but by the acute withdrawal of estrogen.
• During the perimenopause, estrogen levels can
  decline suddenly, severely, and repetitively

43
2. The diagnosis of the perimenopause can usually
be made from the patients history it rarely
requires measurement of follicule-stimulating
hormone

• Measuring the FSH level of a perimenopausal women
  is like taking a photograph of the speedometer of
  car it reflects reality at that moment but
  rapidly becomes obsolete information
• A classic history like this patients is enough
  to make a diagnosis

44
3. Low-dose oral contraceptives offer nonsmokers
many benefits

• Estrogen component relieve hot flash
• progestin component provide regular and light
  withdrawal bleeding as well as contraceptive
  efficacy

45
4. Know the contraindications of oral
contraceptives

• Smoker
• pregnant
• have a history of thromboembolic or liver disease
• have breast and endometrial cancer
• abnormal bleeding warrants evaluation before
  starting treatment

46
5. For perimenopausal women who cannot or will
not take oral contraceptives, supplemental
estrogen can provide relief

• Very often, 0.3 mg conjugated estrogen daily will
  provide relief
• concomitant progestin is usually not required if
  the patient has regular menses
• However, when she becomes oligoovulatory, she
  will need to add a progestin --- this can cause
  irregular bleeding

47
6. Switch from oral contraceptives to
conventional cyclic HRT when you think the
patient has become menopausal

• The incidence of irregular bleeding in newly
  postmenopausal women given continuous HRT is high
• Bleeding would be less of problem with cyclic
  treatment
• Finding appropriately-timed bleeding on cyclic
  HRT usually indicated that the patient has become
  menopausal