GYNECOLOGY

Topic: Menopause
Lecturer: Dr. Garcia (RCG)

MENOPAUSE Enzymatic
 Permanent cessation of menstruation caused by failure of ovarian  Galactosemia – major cause
follicular development and estradiol production in the presence of  17α-hydroxylase deficiency (limiting step in the production of
elevated gonadotropin levels testosterone)  defect in sex steroid production  sexual infantilism
 Defined by last menstrual period and hypertension
 Cessation of menses is variable Immune
 May occur prior to cessation of menses, seldom a precise time of this  Virtually all autoimmune disorders are associated with POF
event
Gonadotropin Effects
Factors Affecting Onset:  Abnormalities in structure, receptors, or in receptor binding such as an
 Women across the world will have differing ages of the occurrence of abnormality in FSH receptor binding
menopause. Even the build and specific characteristics of a woman
would dictate the onset of menopause Ovarian Insults
 Younger menopause  Ionizing radiation (~800 rads), overly aggressive ovarian surgery (e.g.
o (Earlier than 51 yrs. Old): correlate with socioeconomic status oophorocystectomy), or chemotherapy (cyclophosphamide – most
 Higher Parity toxic)
o Late menopause  Viral infections – mumps
 Smoking
o 1-2 years earlier onset Idiopathic
 BMI  Majority of women with POF since no demonstrable cause
o Late onset (data is not consistent)  Or mutations in genes in the X chromosome
 Physical or Athletic Activity
o No influence on age of onset of menopause MANAGEMENT
 Ethnicity:  Screen for autoimmune disease
o Western countries – 51-52 yrs; correlate with general health  Karyotype
o White Americans - 51-53 years  TVS – size of ovaries (follicular activity)
o Black and Hispanic Americans - Earlier by 2 years compared to  Replacement with Estrogen  wanting to conceive  and until natural
Whites menopause
o Malay - 45
o Thai - 49.5 To address the long-term risk of osteoporosis & CVD
o Filipina - 47-48
o Indians - Mid to Late 40’s MENOPAUSAL TRANSITION (Perimenopause)
 Countries at higher altitude  2 phases:
o Earlier by 1-1.5 years o Early
o Late
The primary determinant of age of menopause is GENETIC!!!  These changes signify varying period of time during which rapid oocyte
depletion cause hypoestrogenism
 Time between onset of irregular menses
PREMATURE OVARIAN FAILURE/INSUFFICIENCY (POF/POI)
 Explaining the dwindling amount of estrogen
 Defined as the hypergonadotropic ovarian failure occurring prior to 40
years old
Ovarian Changes
 Occurs in 5-10% of women evaluated for amenorrhea
Gametogenic Ovarian Failure
 Overall prevalence in general population: 0.3-0.9%
 Marked diminution of reproductive activity
 Decreased AMH, Inhibin B levels, antral follicle counts
Possible Causes:
 Rising FSH
 Genetic
Inhibin inhibits FSH production  naturally, FSH decreases
 Enzymatic
 Immune
 Slow decline in androgen status – largely a phenomenon of aging
 Gonadotropic Defects
Due to ovaries & adrenals (granulosa and lutein cells), the decline is
 Ovarian Insults just secondary to the aging process
 Idiopathic
 Functional capacity of the ovary is also diminished
Causes of POF  Inhibin B – lower levels in early follicular phase of women in late 30s;
Genetic Total production is decreased in women >35 y.o.
 Primary determinant  Decreasing levels of Mullerian Inhibiting Substance (MIS) or AMH
 Defective X chromosome  Gonadal dysgenesis  increased rate of This is a new marker for dictating whether there is ovarian reserve
atresia depletion
So for us to maintain a normal cyclicity  we should have normal 2
X’s. If only 1 is functioning  may cause POF  General decline in oocyte number with age
 Elevated activin
 Mutations in genes encoding the FSH receptor (granulosa cells) Activin – ↑FSH receptors  ↑FSH
 Functional mutations of antimullerian hormone (AMH)
 Dystrophic myotonia  Major reduction in ovarian estrogen production

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 GYNECOLOGY
Topic: Menopause
Lecturer: Dr. Garcia (RCG)

Hormonal Changes Bone Effects of Menopause

 Marked reductions in estradiol (E2) and estrone (E1)  OSTEOPOROSIS – a health care problem
o E2 levels average 15 pg/mL (10-25 pg/mL) - < 10 in women who  Estrogen (is decreased):
have undergone oophorectomy o Suppress bone turnover by ↑ osteoclast apoptosis
o E1 levels average 30 pg/mL – higher in obese women o Involve the inhibition of production of proinflammatory
Remember that with the fat pads  it has the ability to cytokines which leads to increased resorption
convert peripherally the androgens to estrogen  higher o Estradiol upregulates TGF-B in bone which inhibits bone
levels of estrone in obese as compared to estradiol resorption
o Dual-energy x-ray absorptiometry (DEXA) scans – standard of
 GH, TSH, and ACTH are normal care for detection of osteopenia and osteoporosis
 Serum prolactin levels may slightly be decreased (influenced by  DEGENERATIVE ARTHRITIS
estrogen status) o Degeneration of intervertebral discs
 Postmenopausal ovary and adrenal gland continue to produce  OSTEOARTHRITIS
androgen o Damage to chondrocytes
o Ovary – continues production of androstenedione and
testosterone but not E2 Cardiovascular Effects of Menopause
o Adrenal gland – continues production of androstendione,  Increased risk for CVD –
DHEA, and DHEA-S  Accelerated rise in total cholesterol from elevated LDL-C
 Sex hormone-binding globulin (SHBG) levels decrease  relatively  Other changes that contribute to the increased risk of CVD:
higher levels of bioavailable testosterone o Blood flow in all vascular bed decreases after menopause
o Prostacyclin production decreases
EFFECTS OF MENOPAUSE ON DIFFERENT ORGAN SYSTEMS o Endothelin levels increase
CNS
 Brain is an active site for estrogen action and estrogen formation CANCER RISK IN POSTMENOPAUSAL WOMEN
 Estrogen is basically neuroprotective – it has neurotropic action to the Breast Cancer
CNS  Borderline or small statistical increase risk among estrogen therapy
 Activity mediated via estrogen receptor alpha but predominantly beta users (related to dose and duration) but GREATER RISK with the
in the frontal & parietal cortex addition of progesterone
 Estrogen deficiency will result to: In the absence of uterus and you keep on giving estrogen +
o Hot flush "vasomotor episode” – hallmark progesterone replacement therapy  you put the woman at
o Nocturnal sleep disruption greater risk of breast cancer because the addition of progesterone
o Depression increases mammary tissue proliferation and activity
o Cognitive decline: So in the absence of uterus, you are good with giving estrogen alone
 Dementia (Alzheimer's disease)
Endometrial Cancer
Collagen and Other Tissues  Increased in women using unopposed estrogen therapy
 ESTROGEN If you are giving estrogen therapy in a woman with uterus, and is
o Positive effect on collagen not being given a progesterone component  ugly effect of
o Important component of bone and skin estrogen (which is unopposed) is that causes proliferation of
endometrium = possible endometrial cancer
o Major support tissue for the structures of the pelvis and
So you should give progesterone + estrogen if woman has a uterus
urinary system
 Effects:
 Precursor lesion (endometrial hyperplasia) alerts the presence of an
o Skin thickness reduction (glistening skin)
abnormality
o Bone loss
 Usually, if it occurs, of a well-differentiated and hormonally responsive
o Osteoporosis
grade or type
o Reductions in collagen support on pelvic floor and urethral
mucosa → prolapse urinary incontinence and irritative bladder
Ovarian
symptoms
 Relative risk is less than two-fold
 Estrogen therapy – restoration of bladder control; decrease recurrence  Conflicting data if confounders were considered and no association
of UTI; normal wound healing with duration of use
 Conflicts with an established fact that OCPs are known to DECREASE
Vulvovaginal Atrophy ovarian cancer risk
 Dryness and atrophic changes occur in 21% and 15% of women
 Estrogen deficiency results in a: Colorectal
o thin, paler vaginal mucosa  A consistent data on the use of hormone therapy of 33% reduction in
o low moisture content the risk for this type of cancer
o Alkaline pH
o Mucosal inflammation
o small petechial lesions

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 GYNECOLOGY
Topic: Menopause
Lecturer: Dr. Garcia (RCG)

HORMONE REGIMEN PREVENTING OSTEOPOROSIS

Estrogen Estrogen/ Estrogen+ Progestogens
 Steroid hormone, derived from androgenic precursors  Selective estrogen receptor modulators (SERMs)
 Low doses are recommended for control of hot flushes, dryness or  Bisphosphonates
dyspareunia (via vaginal route) and may be sufficient to prevent bone  Calcitonin 50 IU SQ daily or 200 intranasally
loss  Fluoride- increases bone density
 Synthetic estrogens, given orally, are more potent than natural E2  Intermittent Parathyroid hormone
(estradiol)  Adjunctive measurements:
 Oral estrogens have a potent hepatic “first-pass” effect that results in o Calcium
loss of activity by 30% o Vit. D (through sunlight)
Progesterone o Exercise
 ORAL:
o Medroxyprogesterone acetate Lecture Discussion: Preventing Osteoporosis
o Norethisterone If you would want to address Osteoporosis and prevent it, there is such a
o Micronized progesterone thing as the “Golden period of opportunity”  within 10 years from the time
 Progestogen administered vaginally – Mirena of the onset of menopause
 If you are able to give the estrogen + progesterone therapy or
Androgen Therapy SERMs  for the first 10 years (meaning to say if menopause is at
 For complaints or problems relating to libido and energy 50 ~ up to 60 years of age) you are able to give your estrogen
 Oral, patch or gel replacement, this will be the greatest time where your patient will
benefit from bone protection, cardiovascular protection as well as
ALTERNATIVE THERAPIES FOR MENOPAUSE CNS affectation
1. Antidepressants (SSRIs/SNRIs)
 Paroxetine
o Only product currently approved by FDA
In the US, since Paroxetine is mainly used for depression
and anxiety, there is a big hype for Fluoxetine
o Moderate effect
o Interfere in Tamoxifen therapy
2. Gabapentin
 300-900 mg
 Superior to placebo
 SE: somnolence, dizziness, fatigue, ataxia
3. Antihypertensives
 CLONIDINE 0.1 mg patch daily
o Most studied; efficacy is not very large
4. Phytoestrogens
 Class of plant-derived estrogen-like compounds conjugated to glycoside
moieties
 Questionable efficacy and safety
 ISOFLAVONE 60mg: large daily doses, limited efficacy in hot flushes
 RED CLOVER and BLACK COHOSH: similar effects as placebo
Black Cohosh has been found to be effective in hot flushes, bone
protection, skin integrity. However, big clinical trials are still wanted
to come up with its efficacy and use in the menopause
5. Cognitive Behavior Therapy
 “Talk therapy” : teaches coping skills; beneficial
Used for those who are contraindicated with the use of hormonal
therapy
6. Acupuncture
 Treatment of hot flushes and other menopausal symptoms
 Effective in alleviating the frequency and severity of hot flushes
7. Stellate Ganglion Blockade
 Invasive; effective in some women treated for breast cancer
 Image-guided stellate ganglion blockade with 5mL of 0.5%
 BUPIVACAINE : beneficial

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