Prof.

Dr Muhammad Aslam
Objectives
After attending this lecture, the student will be able to:
 Define perimenopause and menopause
 Diagnose menopause in a woman
 Draw management plan for a symptomatic
menopausal woman
 Describe the indications, contraindications and
side effects of HRT
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Menopause
 Permanent cessation of menses for 1 year due to ovarian
follicle inactivity in the presence of adequate gonadotrophin
stimulation
 Climacteric (perimenopause) transition phase during which
ovarian function regresses
 Menopause is diagnosed retrospectively after 12 months of
amenorrhea
 Age ranges ~ 43-57 years (Average age = 51)
 Premature menopause ~ before 40 years
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Pathophysiology of menopause
 As the ovary ages → the remaining follicles become
less sensitive to gonadotrophins → ovulation declines
→ ovarian function gradually fails
  in inhibin production by the ovary. Inhibin inhibits
production of FSH → plasma FSH levels start to 
 The E2 level falls → insufficient to stimulate
endometrial proliferation and menopause ensues
 Further decline in E2 levels over subsequent years
affects all E2-responsive tissues in the body
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Diagnosis
Clinical history (hot flashes)
Clinical exam (tissue atrophy)
 FSH

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Further assessment
Breast screening and mammography
Endometrial assessment in case of unscheduled
bleeding
Cardiovascular disease risk assessment
Skeletal assessment including bone density
estimation and fracture risk assessment

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Menopausal Symptoms
Vasomotor symptoms
• Hot flashes
• Night sweats
• Sleep disturbance
Osteoporosis
Urogenital atrophy
• Dyspareunia, atrophic vaginitis
• Urethral syndrome
Cardiovascular
Mood changes
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Hot flashes
 Vasomotor instability
 Feeling of intense body heat; reddening of the skin
over face, neck, and chest; profuse sweating
 Treatment:
• Hormone replacement therapy (HRT)
• Selective serotonin reuptake inhibitors
• Clonidine
• Gabapentin
• Medroxyprogesterone acetate
• Soy, black cohosh, Evening primrose, Dong quai
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Urogenital Atrophy
 loss of estrogen ~ urogenital atrophy
 Vaginal shortening, narrowing and dryness ~
dyspareunia, atrophic vaginitis
 Urethral syndrome ~ dysuria, urgency, UI
 Treatment
• HRT
• Vaginal estrogen
• Water based lubricants
• Soybean isoflavones, chasteberry, ginseng
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Osteoporosis
Estrogen inhibits bone
resorption
Menopause ~
bone resorption & bone formation
Resultant bone fragility ~  risk of fractures
Defined as BMD of ≤ --2.5

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Osteoporosis
Loss of height
Kyphosis
Spinal compression
fractures
Tendency to fractures
Typical short hunch-backed old lady appearance

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Risk Factors for Osteoporosis
 Family H/O osteoporosis  Anorexia nervosa
 Family H/O osteoporotic  Dietary deficiency of
fracture calcium and vitamin D
 Caucasian/Asian women  Excessive alcohol intake
 Advanced age  Current low bone mass
 Low body weight  Reduced physical activity
 Smoking  Medications, including
 Menopause steroids, GNRH analogs,
 Premature menopause or anticonvulsants, long-term
bilateral oophorectomy heparin, excessive thyroid
hormones, cholestyramine
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Treatment of Osteoporosis
 HRT – not preferred
 Bisphosphonates (Alendronate, Risedronate,
Ibandronate)
 Selective estrogen receptor modulators (SERMs) --
Raloxifene
 Calcitonin
 Parathyroid Hormone
 Life style changes, cessation of smoking, increased
dietary calcium intake and weight bearing exercise
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Cardiovascular Disease
Estrogen is protective against CVD by:
• Maintaining  high density lipoproteins,  low
density lipoproteins
• Direct arterial vasodilatation
Prevention:
• Antihypertensive & lipid control medications
• Smoking cessation
• Weight loss & Exercise
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Mood Disturbances
Fatigue, nervousness, headaches, insomnia,
depression, & irritability are frequent during
menopause
Causal relation with E2 withdrawal is uncertain –
Empty nest syndrome
Treatment:
 HRT & SSRIs
 St. John’s wort & Black cohosh
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Hormone Replacement Therapy

Estrogen alone or in combination with progesterone

is prescribed to relieve hormone deficiency at
menopause

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History taking prior to HRT
 Detailed Medical & Gynecological history
 Personal and familial breast disease
 Diabetes & Hypertension
 Venous and arterial thromboembolic disease
 Liver disease
 Gastrointestinal disease
 Family history of osteoporosis, ovarian cancer
and colonic cancer
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Investigations prior to HRT
Measure height and weight
Blood pressure
Breast examination
Mammography (if needed)
Abdominal examination
Vaginal and pelvic examinations
Cervical smear
Lipid profile
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Indications of HRT

• Vasomotor symptoms
• Genitourinary symptoms

• Prevent vaginal–urethral mucosal atrophy

• Maintain skin collagen
• Reduce bone resorption
• Protect the cardiovascular system
• Maintain brain cognitive function
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Uterine

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Types of HRT Regimen
Cyclic
Sequential
Long cycle
Continuous combined
Gonadomimetic

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Drug
Oral estrogens
Ethinyl estradiol (Estinyl)
Conjugated Equine Estrogen
(Premarin)
Oral progestins
Medroxyprogesterone acetate
– MPA -- (Provera)
Norethindrone acetate
Dosage
0.02-0.05 mg daily
0.3-1.25 mg daily
10mg/day x 12 d/month or
2.5-5.0 mg daily
2.5-10mg x 12 days/month
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Drug Dosage
Oral Estrogen/progestin combinations
Continuous
Conjugated E2+ MPA 0.3/1.5 mg/daily, 0.45/1.5
(Prempro) mg/daily, 0.625/2.5 mg daily or
0.625/5 mg daily
Cyclical
Estradiol/norgestimate 1 mg estradiol for 15 d, and then
(Ortho-Prefest) 1 mg estradiol/0.99 mg
norgestimate for 15 d
Conjugated E2 + MPA 0.625 conjugated E2 for 14 d,
(Premphase) then 0.625 conjugated E2/ 5
mg MPA for 14 d
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Drug Dosage
Transdermal
Transdermal estradiol 0.025- 0.1 mg/d, Apply once
(Estraderm) or twice a week
Transdermal estrogen/ 0.05/0.14 mg or 0.05/0.25
progestin (CombiPatch) mg weekly
Vaginal
Estrogen creams, tablets Variable dosing
and ring
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Minor Side Effects of HRT
Nausea and vomiting Weight gain
Headaches Fear of cancer &
Leg cramps general anxieties about
Bleeding treatment
Mastalgia
Bloating
Fluid retention

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Major Side Effects of HRT
Venous thromboembolism
Breast cancer
Endometrial cancer

HRT protects against colorectal cancer

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Take Home Assignment
What are the contraindications to the use of HRT?

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Key Points
 The mean age of menopause is 51
  levels of estrogen
 Women develop amenorrhea, hot flashes, vaginal
atrophy, mood and sleep changes
 Dx. is clinical. Can be confirmed by  levels of FSH
 In women who still have uterus, both estrogen and
progesterone should be used to avoid endometrial
carcinoma
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