mnagement of menopause by hmc FM residents

1. Management of Menopause
By Dr. Amir M Hanafi
Under supervision of Dr. Abeer

2. Case scenario
• A 51-year-old woman has a complaint that
her menses are becoming less frequent than
they used to be, every 45 days compared to
every 32 days before, she also complains of
frequent and distressing hot flashes that
interfere with her work and sleep, and
vaginal dryness that makes sexual intercourse
with her husband uncomfortable. She is
otherwise healthy.

3. • How do you diagnose menopause?
• What’s the differential diagnosis?
• What are the most common problems?
• What’s the proposed management of those
problems?

4. Introduction
• Natural menopause is the permanent
cessation of menses, after a woman has 12
months of amenorrhea without any other
cause.
• It occurs at a median age of 51.4 years in
normal women, and is a reflection of ovarian
follicular depletion, with hypoestrogenemia
and high FSH.

5. Introduction
• Menopause before age 40 years is considered to
be abnormal and is referred to as primary ovarian
insufficiency (premature ovarian failure).
• The menopausal transition, or perimenopause,
occurs after the reproductive years, but before
menopause, and is characterized by irregular
menstrual cycles, endocrine changes, and
symptoms such as hot flashes.

8. Diagnosis – S/O
• Hot flashes — The most common symptom
during the menopausal transition and
menopause
– occur in up to 80 percent of women in some cultures.
– only about 20 to 30 percent of women seek medical
attention for treatment.
– Some women first develop hot flashes that cluster
around menses during their late reproductive years,
but symptoms are typically mild and do not require
treatment.

9. • Sleep disturbance — women experience sleep
disturbances even in the absence of hot flashes.
• The estimated prevalence of difficulty sleeping based
upon two longitudinal cohort studies was 32 to 46%.
• Anxiety and depression symptoms may also contribute
to sleep disturbances; in one study, they were
predictive of subjective sleep disturbances.
• In addition, perimenopausal women with hot flashes
are more likely to be depressed. Primary sleep
disorders are also common in this population.

10. • Depression — A number of reports indicate that there
is a significant increased risk of new onset depression
in women during the menopausal transition compared
with their premenopausal years. The risk then
decreases in the early postmenopause.
• In a study to determine risk factors for depressive
disorders, a diagnosis of depression was 2.5 times
more likely to occur in the menopausal transition
compared with when the woman was premenopausal
(odds ratio [OR] 2.50; 95% CI 1.25-5.02).

11. • Vaginal dryness — The epithelial lining of the
vagina and urethra are estrogen-dependent
tissues, and estrogen deficiency leads to
thinning of the vaginal epithelium. This results
in vaginal atrophy (atrophic vaginitis), causing
symptoms of vaginal dryness, itching, and
often dyspareunia.

12. • The prevalence of vaginal dryness in one
longitudinal study was 3, 4, 21, and 47 percent
of women in the reproductive, early
menopausal transition, late menopausal
transition, and three years postmenopausal
stages, respectively.

13. • Early in the menopause transition, women
may notice a slight decrease in vaginal
lubrication upon sexual arousal, which is often
one of the first signs of estrogen insufficiency.

14. • Sexual function — The cervix also can atrophy
and become flush the vaginal vault. The elasticity
of the vaginal wall may decrease and the entire
vagina can become shorter or narrower.
• Continuing sexual activity may prevent these
changes in size and shape of the vagina, even in
the absence of estrogen therapy .
• Symptoms related to genitourinary atrophy are
exquisitely responsive to estrogen therapy, in
particular, vaginal estrogen therapy.

15. • Cognitive changes — Women often describe
problems with memory loss and difficulty
concentrating during the menopausal transition
and menopause, and substantial biologic
evidence supports the importance of estrogen to
cognitive function.
• A decline in cognitive function was not observed
in the SWAN study, but increases in anxiety and
depression had independent, unfavorable effects
on cognitive performance .

16. • Joint pain — While women who are obese or
depressed are more likely to experience joint
pain, there also appears to be an association
with menopausal status, with peri- and
postmenopausal women experiencing more
joint pain than premenopausal women.

17. • It is unclear if the pain is related to estrogen
deficiency or a rheumatologic disorder, but in
the Women's Health Initiative, women with
joint pain or stiffness at baseline were more
likely to get relief with either combined
estrogen-progestin therapy or unopposed
estrogen than with placebo.

18. • Other
– Breast pain – Breast pain and tenderness are common
in the early menopausal transition, but begin to
diminish in the late menopausal transition. This is
probably due to the fluctuations in serum estradiol
concentrations.
– Menstrual migraines – Menstrual migraines are
migraine headaches that cluster around the onset of
each menstrual period. In many women, these
headaches worsen in frequency and intensity during
the menopausal transition.

19. Diagnosis summary
• In normal, healthy women over age 45 years:
– We make the diagnosis of the menopausal transition
or “perimenopause” based upon a change in
intermenstrual interval with or without menopausal
symptoms.
– A high serum follicle-stimulating hormone (FSH)
concentration is not required to make the diagnosis.
– We diagnose menopause as 12 months of
amenorrhea in the absence of other biological or
physiological causes.

20. • In women between the ages of 40 and 45
years:
– same as that for women over 45 years, except that
other causes of menstrual cycle dysfunction must
first be ruled out (eg, endocrine evaluation for
non-menopausal causes of oligo/amenorrheamust
be normal including serum human chorionic
gonadotropin [hCG], prolactin, and thyroid
stimulating hormone [TSH]).

21. • For women under age 40 years:
– Women in this age group should not be diagnosed
with either the menopausal transition or
menopause. They have primary ovarian
insufficiency (premature ovarian failure).

22. • Special situations
– Women with underlying menstrual cycle
disorders — the STRAW staging system does not
apply to women with underlying menstrual
disorders such as polycystic ovary syndrome
(PCOS) or hypothalamic amenorrhea. we suggest
measuring FSH concentration for diagnostic
purposes.

23. • Women taking oral contraceptives — We suggest
stopping the pill and measuring serum FSH two to
four weeks later. A level ≥25 IU/L indicates that the
patient has likely entered the menopausal transition.
However, there is no FSH value that would provide
absolute reassurance that she is postmenopausal.

24. • Post-hysterectomy or endometrial ablation —In this
setting, we suggest measurement of FSH
concentration. A serum FSH >25 IU/L, particularly in
the setting of hot flashes, is suggestive of the late
menopausal transition. For a postmenopausal
woman, FSH would be considerably higher (in the 70
to 100 IU/L range).

25. DIFFERENTIAL DIAGNOSIS
• Hyper/hypothyroidism
• Pregnancy
• hyperprolactinemia,
• Medications
• Carcinoid
• Pheochromocytoma
• underlying malignancy.

27. Treatment – Risk factors for VMS
•Obesity
•Smoking
•Reduced physical activity
•Socioeconomic factors
•Hormonal concentrations – Annual serum follicle-
stimulating hormone (FSH) levels is associated with both
the prevalence and frequency of VMS.
•Ethnic factors – African-American women report more
frequent hot flashes than Caucasian women,
and Japanese and Chinese women less so.

28. TREATMENT – NON HORMONAL
• simple behavioral measures, such as:
• lowering room temperature
• using fans
• dressing in layers of clothing that can be easily
shed
• avoiding triggers (such as spicy foods and
stressful situations)
• Some clinicians recommend vitamin E to women
with mild hot flashes because, at low doses, it is
well tolerated and not associated with toxicity.

29. TREATMENT- INCONSISTENT EVIDENCE
• Isoflavones present in soy containing foods.
• Black cohosh ‫األسود‬ ‫الثعبان‬ ‫جذور‬
• Acupuncture
• Paced respiration
• Mind-body based therapies
• Weight loss
• Exercise

30. TREATMENT - INEFFECTIVE
• Evening primrose oil (EPO)
• Flaxseed ‫الكتان‬ ‫بذور‬
• Other: ginseng or dong quai, Wild yam and
progesterone creams ,Traditional medicinal
Chinese herbs, reflexology, and magnetic
devices have all been studied and appear to
have no beneficial effect.

31. TREATMENT - HORMONAL
• The goal of MHT is to relieve menopausal
symptoms, most importantly hot flashes
(vasomotor symptoms).
• In the past, hormone therapy (HT) was also used
long-term for prevention of chronic disease
(coronary heart disease [CHD] and
osteoporosis). However, we do not recommend
HT for prevention of disease, given the results of
the Women’s Health Initiative (WHI), a set of
two large randomized trials that demonstrated
an unfavorable risk-benefit profile of HT.

32. TREATMENT - HORMONAL
• Candidates/indications for most women in their
late 40s or 50s with moderate to severe
vasomotor symptoms with the exception of those
with a history of:
– breast cancer
– CHD
– a previous venous thromboembolic event or stroke
– active liver disease
– those at high risk for these complications.

33. TREATMENT - HORMONAL
• Inconsistent benefit:
– Vaginal atrophy
– Depression
– Joint aches and pains
– Cognitive function and dementia
– Prevention dementia.
– Prevention of CHD.
– Osteoporosis: we now recommend
bisphosphonates.

34. TREATMENT - HORMONAL
• Estrogen therapy remains the gold standard
for relief of menopausal symptoms, in
particular, hot flashes.
• All routes of administration appear to be
equally effective for symptom relief (and bone
density), but their metabolic effects differ.

35. • Oral estrogen has more favorable effects on lipid
profiles, but there is no evidence that this results
in long-term clinical benefit.
• On the other hand, oral estrogens are associated
with:
– negative impact on libido and sexual function, but this
has not been proven.
– Similar effects on thyroid-binding globulin (TBG):
increased TBG and lower bioavailable T4.
– Lastly, the risks of venous thromboembolism (VTE)
and stroke appear to be higher with oral when
compared with transdermal estrogen.

36. • We suggest transdermal 17-beta estradiol for
most women because of the potential
advantages outlined above, However, the
baseline risk of both VTE and stroke is very
low in otherwise healthy, young
postmenopausal women. Therefore, if a
patient prefers an oral preparation over a
transdermal one (cost or personal preference),
we consider oral estrogen to be safe.

37. • In addition to oral and transdermal estrogen
preparations, estrogen is available as a vaginal
ring and as a topical spray, cream, or gel. The
topical spray has been linked to adverse
effects in children and pets exposed to the
drug via skin contact.

38. TREATMENT - HORMONAL
• Dose — We typically begin with a transdermal estradiol
0.025 mg patch (or if using oral estradiol, 0.5 mg/day).
• If hot flashes are still present after one month, we
increase transdermal estradiol to 0.0375 mg and
reassess one month later.
• If symptoms are still not relieved, we increase further
to 0.05 mg.
• An exception to this approach is the patient with
severe symptoms; we start with a transdermal dose of
0.05 mg to achieve more rapid relief of symptoms.

39. • “Standard” doses of estrogen given daily
(Conjugated Estrogen 0.625 mg or its
equivalent) are sufficient to reduce hot flash
frequency and severity by approximately 75
percent relative to placebo.
• In a systematic review and meta-analysis, CE
and 17-beta estradiol (oral or transdermal)
were equally effective.

40. • Estrogen should be administered
continuously; past regimens where estrogen
was administered days 1 to 25 of the calendar
month are considered to be obsolete.
• Women will often get hot flashes during the
days off, and there is no known advantage to
stopping for several days each month.

41. • These doses of estrogen are adequate for
symptom relief in the majority of women. An
exception is younger women after bilateral
oophorectomy.
• They often require higher doses (eg, up to 0.1
mg transdermal estradiol) for the first two to
three years after surgery; the dose can
subsequently be tapered down.

42. • Factors affecting oral estrogen metabolism :
• The above dosing suggestions may need to be increased in:
– women taking anticonvulsant drugs
(phenytoin, carbamazepine), which increase the hepatic
clearance of estrogens. However, there is no way to predict how
much more estrogen is needed so a transdermal estrogen may
be better since it avoids the first pass hepatic metabolism.
– In women receiving T4 replacement therapy, the addition of oral
estrogen therapy may increase T4 requirements.
• The above dosing suggestions may need to be decreased
in:
– Concurrent acute alcohol ingestion.
– Women with end-stage renal disease.

43. Adding a progestin
• All women with an intact uterus need a progestin
in addition to estrogen to prevent endometrial
hyperplasia, which can occur after as little as six
months of unopposed estrogen therapy (ET).
• While MPA is endometrial protective, it was
associated with an excess risk of coronary heart
disease (CHD) and breast cancer.
• In addition, regimens using continuous versus
cyclic MPA may be associated with a higher risk of
breast cancer.

44. • An alternative progestin, natural micronized
progesterone, is also considered to be
endometrial protective (200 mg/day for
12 days/month or 100 mg daily
• In practice, we prescribe oral micronized
progesterone as our first-line progestin.

45. • For women who are perimenopausal or newly
menopausal, we start with cyclic
administration. Continuous administration in
this population is associated with irregular,
unscheduled bleeding due to the exogenous
hormones and the continued endogenous
ovarian function.

46. • For women who are ≥2 to 3 years
postmenopause, we use a continuous
regimen. While there is often early
breakthrough bleeding even after menopause,
most women do eventually develop
amenorrhea, a desired goal of continuous
administration

47. • Mood symptoms and/or withdrawal
bleeding — Some women are unable to
tolerate cyclic progestin administration
because of mood side effects, bloating and
monthly bleeding.
• For any of these concerns, we suggest
switching to a continuous regimen. However,
for women who are newly menopausal,
breakthrough bleeding can be anticipated.

48. • Women who cannot tolerate oral
progestins — Some women are unable to
tolerate any oral progestin, whether given in a
cyclic or continuous regimen. In this case, we
often suggest off-label use of the lower dose
levonorgestrel-releasing intrauterine device
(IUD).

49. • Duration — Short-term therapy is considered
to be two to three years, and generally not
more than five years.
• Only the minority of women who are unable
to successfully discontinue estrogen (because
of persistent symptoms) should consider
extended use of estrogen therapy.

50. • Side effects — Common side effects of estrogen
include breast soreness, which can often be
minimized by using lower doses.
• As noted above, some women experience mood
symptoms and bloating with progestin therapy.
• Vaginal bleeding occurs in almost all women
receiving cyclic estrogen-progestin regimens and
is common in the early months of continuous
estrogen-progestin regimen.

51. STOPPING HORMONE THERAPY
• Abrupt withdrawal of exogenous estrogen at any age may
result in (55%) the return of hot flashes and other
menopausal symptoms.
• When tapering, one suggested approach is to decrease the
estrogen by one pill per week (ie, six pills per week, then
five pills per week, etc) until the taper is completed. The
progestin is tapered on the same schedule.
• In our experience, women who are unable to tolerate a six-
week taper temporarily resume their estrogen, and we
then try a much slower taper, sometimes over one year (six
pills per week for two months, five pills per week for one
month, etc).

52. • Managing recurrent symptoms — In women who have
recurrent vasomotor symptoms after stopping therapy,
there is currently no way to determine whether the
symptoms will resolve quickly or persist for a prolonged
time.
• In women who develop recurrent hot flashes, we first
encourage them to monitor their symptoms over the
subsequent few months to see if they resolve or improve.
• If there is no improvement, or if the recurrent flushes
during or immediately after the taper are difficult to
tolerate, we try a non-estrogen alternative, such as a
selective serotonin reuptake inhibitor (SSRI) or gabapentin.

53. Special Issues
• Migraines — not considered to be a
contraindication to menopausal hormone
therapy (MHT).
• For women with hot flashes and estrogen-
associated migraines (which typically worsen
during perimenopause), estrogen therapy often
improves both symptoms.
• In this setting we suggest continuous transdermal
hormone regimens (as opposed to cyclic
regimens) to avoid triggering estrogen-
withdrawal headaches.

54. • Depression — The risk of depression during perimenopause is
higher than during the pre- or postmenopausal years.
• Selective serotonin reuptake inhibitors (SSRIs) are effective for
perimenopausal depression, and some provide modest benefit for
hot flashes as well.
• Our approach is to choose initial therapy based upon the woman’s
predominant symptom. If her main concern is depression, and hot
flashes are not severe, we start with an SSRI.
• On the other hand, if vasomotor symptoms are the major symptom
and depression or mood symptoms are mild, we start with HT.
• For women in whom depression and vasomotor symptoms are both
severe, we start both estrogen and an SSRI and refer to a
psychopharmacologist for further consultation and monitoring.

55. • Primary ovarian insufficiency — HT is started
at a younger age in these women, and current
guidelines suggest that therapy should be
continued until the average age of menopause
(age 50 to 51 years) to prevent premature
bone loss, coronary heart disease (CHD), and
stroke.

56. • Breast cancer patients experience early
menopause due to adjuvant chemotherapy
and may have vasomotor symptoms due
to tamoxifen therapy.
• We therefore do not recommend estrogen for
women with a personal history of breast
cancer.

57. • Known thrombophilia — MHT increases the risk
of venous thrombosis by approximately twofold.
• This appears to be true for oral preparations, but
perhaps not for transdermal preparations.
• Data suggest that women who have factor V
Leiden and use oral HT have a 15-fold increased
risk of venous thromboembolism (VTE).
• Therefore, HT should be avoided in
postmenopausal women with prothrombotic
mutations.