Hormone replacement therapy in post menopausal women.

1. Hormone Replacement
Therapy (HRT) in
Postmenopausal women
MAYURI
17M6536

2. Contents
Menopause – endocrinology, symptoms
Hormone replacement therapy (HRT) – indications, benefits,
risks, contraindications
Preparations for HRT
Duration of HRT
Progress in HRT

3. What is Menopause?
Definition - Menopause means permanent cessation of menstruation at the end of reproductive life
due to loss of ovarian follicular activity. It is the point of time when last and final menstruation occurs.
Age – between 45-55 years.
The clinical diagnosis is confirmed following stoppage of menstruation (amenorrhea) for 12
consecutive months without any other pathology.

4. Endocrinology of Menopause
Depletion of Ovarian follicles and its resistance to FSH, LH.
Impaired folliculogenesis
Decreased Estradiol
production
Decreased negative feedback
effect on HPA axis
Increased FSH levels
Decreased Inhibin
release

5. hormone Levels in menopause
Estradiol 5-25 pg/ml
Estrone 20-70pg/ml
FSH > 40mlU/ml
Androgen 0.3-1.0 ng/ml
Testosterone 0.1-0.5 ng/ml
LH 50-100 mIU/ml
Androstenedione 600 pg/ml
GH, Inhibin B, Anti-Mullerian hormone low

6. ORGANS CHANGES
Ovaries Shrink, wrinkled, white
Fallopian tubes Thinned, no cilia
Uterus Smaller, thin and atrophied endometrium
Vagina Narrow, loss of elasticity, alkaline pH
Vulva Atrophied, flat labia, scanty pubic hair
Breasts Fat reabsorbed, flat, pedunculous, small nipples
Bladder and urethra Prone to damage and infection, dysuria, stress
incontinence
Pelvic floor muscles Muscle tone lost – uterine descent

7. The important symptoms and the health
concerns of menopause are:
1. Vasomotor symptoms – hot flushes, palpitations, fatigue, weakness, perspiration
2. Urogenital symptoms – atrophic changes, dyspareunia, dysuria, UTI, stress incontinence
3. Osteoporosis and fracture – bone mass loss, microarchitectural deterioration of bone tissue,
back pain, loss of height, kyphosis, fractures of the vertebral body, femoral neck and Colle’s
fracture.
4. Cardiovascular and Cerebrovascular effects – atherosclerotic changes, vasoconstriction,
thrombus formation, IHD, stroke.
5. Psychological changes – anxiety, depression, insomnia, irritability, inability to concentrate,
mood disorders
6. Skin and Hair - “Purse string” wrinkling around the mouth and “crow feet” around the eyes,
thinning, loss of elasticity, wrinkling, loss of pubic and axillary hair, slight balding.
7. Sexual dysfunction – due to depression, anxiety
8. Dementia and cognitive decline – Alzheimer’s disease

9. Diagnosis of Menopause
• Cessation of menstruation for consecutive 12 months during climacteric.
• Appearance of menopausal symptoms ‘hot flush’ and ‘night sweats’.
• Vaginal cytology – showing maturation index of at least 10/85/5 (Features of low
estrogen).
• Serum estradiol : < 20 pg/mL.
• Serum FSH and LH: >40 mlU/mL (three values at weeks interval required).

10. Treatment of post-menopausal
symptoms
Non-hormonal
treatment
Hormone
Replacement
Therapy (HRT)

11. Hormone Replacement Therapy (HRT)
The HRT is indicated in menopausal women to overcome the short-term and long-
term consequences of estrogen deficiency.
Indications of Hormone Replacement Therapy:
i. Relief of menopausal symptoms
ii. Prevention of osteoporosis
iii. To maintain the quality of life in menopausal years.
Special group of women to whom HRT should be prescribed:
i. Premature ovarian failure
ii. Gonadal dysgenesis
iii. Surgical or radiation menopause

12. Benefits of hormone replacement therapy
(HRT)
• Improvement of vasomotor symptoms (70– 80%)
• Improvement urogenital atrophy
• Increase in bone mineral density (2–5%)
• Decreased risk in vertebral and hip fractures (25–50%)
• Reduction in colorectal cancer (20%)
• possibly cardioprotection

13. HRT and Osteoporosis:
• HRT prevents bone loss and stimulate new bone formation. HRT
increases BMD by 2–5% and reduces the risk of vertebral and hip
fracture (25–50%).
• Estrogen is found to play a direct role, as receptors have been found in
the osteoblasts.
• Women receiving HRT should supplement their diet with an extra 500
mg of calcium daily. Total daily requirement of calcium in
postmenopausal women is 1.5 g.

14. HRT and Cardiovascular system:
HRT is thought to be cardiovascular protective.
LDL on oxidation produces vascular endothelial injury and foam cell
(macrophage) formation. These endothelial changes ultimately lead to
intimal smooth muscle proliferation and atherosclerosis. Estrogen
prevents oxidation of LDL, as it has got antioxidant properties.

15. Risk factors for osteoporosis in a woman:
• Family history
• Age—elderly
• Race—asian, White race
• Lack of estrogen
• Body weight—low bMI
• Early menopause—surgical, radiation
• Dietary—↓ calcium and ↓ Vitamin D, ↑ caffeine, ↑ smoking
• Sedentary lifestyle
• Drugs—Heparin, corticosteroids, GnRH analogue
• Diseases—Thyroid disorders, hyperparathyroidism malabsorption, multiple
myeloma.

16. Risk factors for cardiovascular disease in
postmenopause:
• Hypertension
• Smoking habit
• Familial hyperlipidemia
• Impaired glucose tolerance

17. Risks of hormone replacement therapy:
a. Endometrial cancer: When estrogen is given alone to a woman with intact uterus, it
causes endometrial proliferation, hyperplasia and carcinoma. It is advised that a
progestogen should be added to ERT to prevent such risks.
b. Breast cancer: Combined estrogen and progestin replacement therapy, increases the
risk of breast cancer slightly, depending upon the dose and duration of therapy.
c. Venous thromboembolic (VTE) disease has been found to be increased with the use
of combined oral estrogen and progestin. Transdermal estrogen use does not have the
same risk compared to oral estrogen.
d. Coronary heart disease (CHD): Combined HRT therapy shows a relative hazard of
CHD.
e. Lipid metabolism: An increased incidence of gallbladder disease has been observed
following ERT due to rise in cholesterol (in bile).
f. Dementia, Alzheimer disease are increased.

18. Contraindications to HRT:
• Undiagnosed genital tract bleeding
• Estrogen dependent neoplasm in the body
• History of venous thromboembolism
• Active liver disease
• Gallbladder disease

19. Available preparations for hormone
replacement therapy:
Estrogens used are: Conjugated estrogen (0.625–1.25 mg/day) or
Micronized estradiol (1–2 mg/day).
Progestins used are: Medroxyprogesterone acetate (2.5–5 mg/ day),
Micronized progesterone (100–300 mg/day) or Dydrogesterone (5–10
mg/day).
Considering the risks, hormone therapy should be used with the lowest
effective dose and for a short period of time.

20. Low dose oral conjugated estrogen 0.3 mg daily is effective and has got
minimal side effects.
Dose interval:
Oral estrogen regime:
• Estrogen—conjugated estrogen 0.3 mg or 0.625 mg is given daily for woman who
had hysterectomy.
• Estrogen and cyclic progestin: For a woman with intact uterus estrogen is given
continuously for 25 days and progestin is added for last 12–14 days.
Daily (initial 2-3
months)
Every other
day (next 2-3
months)
Every 3rd day
(nesxt 2-3
months)

21. Continuous estrogen and progestin therapy:
To prevent endometrial hyperplasia. There may be irregular bleeding with this regimen.
1. Subdermal implants: inserted subcutaneously over the anterior abdominal wall. 17 β
estradiol implants 25 mg, 50 mg or 100 mg are available and can be kept for 6 months. This
method is suitable in patients after hysterectomy.
2. Percutaneous estrogen gel: 1 g applicator of gel, delivering 1 mg of estradiol daily, is to
be applied onto the skin over the anterior abdominal wall or thighs. Effective blood level of
oestradiol (90–120 pg/mL) can be maintained.
3. Transdermal patch: It contains 3.2 mg of 17 β estradiol, releasing about 50 µg of estradiol
in 24 hours. Physiological level of E2 to E1 is maintained. It should be applied below the
waist line and changed twice a week.
4. Vaginal cream: Conjugated equine vaginal estrogen cream 1.25 mg daily is very
effective specially when associated with atrophic vaginitis; reduces urinary frequency,
urgency and recurrent infection. Women with symptoms of urogenital atrophy and urinary
symptoms and who do not like to have systemic HRT, are suitable for such treatment.
5. Progestins: In patients with history of breast carcinoma, or endometrial carcinoma,
progestins may be used. It may be effective in suppressing hot flushes and it prevents
osteoporosis. Medroxyprogesterone acetate 2.5–5 mg/day can be used.

22. • Levonorgestrel intrauterine delivery system (LNG-IUS) with daily
release of 10 microgram of levonorgestrel per 24 hours, it protects
the endometrium from hyperplasia and cancer. At the same time it
has got no systemic progestin side effects.
• Estrogen can be given by any route.
• Tibolone: Tibolone is a steroid (19-nortestosterone derivative)
having weakly estrogenic, progestogenic and androgenic properties.
It prevents osteoporosis, atrophic changes of vagina and hot flushes.
It increases libido. A dose of 2.5 mg per day is given.

23. Monitoring Prior to and During HRT:
• physical examination including pelvic examination.
• blood pressure recording.
• breast examination and Mammography
• cervical cytology
• pelvic ultrasonography (TVs) to measure endometrial thickness (normal <
5 mm)
Any irregular bleeding should be investigated thoroughly (endometrial
biopsy, hysteroscopy).
Ideal serum level of estradiol should be 100 pg/ml during HRT therapy.
Serum level of estradiol is useful to monitor the HRT therapy rather than that
of serum FSH.

24. • Duration of HRT use: Generally, use of HRT for a short period of
3–5 years have been advised. Reduction of dosage should be
done as soon as possible.
• Menopausal women should maintain optimum nutrition, ideal
body weight and perform regular exercise.

25. Progress in hormone replacement therapy:
• Low Dose HRT—Women with intact uterus with 0.3 mg Conjugated equine estrogen
(CEE) and Medroxy Progesterone acetate (MPA) 1.5 mg is found effective to control
the vasomotor symptoms. Similarly 1 mg of estradiol and norethisterone acetate 0.5 mg
orally, are also effective and have significant bone sparing effect. Progestogen is added in
the HRT to minimize the adverse effects of estrogen.
• Dose interval may be modified (as explained earlier) before stopping the therapy.
• To minimize the systemic adverse effects of progestogen, LNG-IUS is being used.
• Estrogen component is delivered by oral or by transdermal route or as an implant. A
small size LNG-IUS has been developed that releases 10 µg LNG per day. This
reduced size LNG-IUS is suitable for the postmenopausal women as the size of the
uterus is also small.

26. Thankyou!