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MANAGEMENT OF POSTMENOPAUSAL SYNDROME.pptx

This document discusses the management of postmenopausal syndrome, detailing the physiological changes during menopause, common symptoms, and treatment options. It outlines the significance of hormone replacement therapy (HRT), the associated risks, and other therapeutic measures for managing symptoms such as hot flashes, osteoporosis, and depression. Additionally, it emphasizes a personalized approach to HRT based on symptom severity and potential risks.

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MANAGEMENT OF POSTMENOPAUSAL SYNDROME BY DR. DEVANSHI THAKKAR JUNIOR RESIDENT 1 DEPT OF PHARMACOLOGY AND THERAPEUTICS KGMU, LUCKNOW
INTRODUCTION • Menopause is defined as the time of cessation of ovarian function resulting in permanent amenorrhea. • It usually occurs between 45 to 60 years of age, 47 being the average age. • The age at menopause appears to be genetically determined and is unaffected by race, socioeconomic status, age at menarche, or number of prior ovulations.
PHYSIOLOGY OF MENSTRUAL CYCLE Hypothalamus secretes GnRH stimulating the pituitary LH, FSH secreted from anterior pituitary FSH secreted stimulates ovarian follicles to release Estrogen and Progesterone.
PHYSIOLOGICAL ACTIONS OF ESTROGEN
PHYSIOLOGY OF MENOPAUSE • During onset of menopause stage, ovarian activity declines. • As ovulation fails, no corpus luteum forms and no progesterone is secreted by the ovary. Therefore all the cycles are anovulatory and irregular. • Later, Graafian follicles also fail to develop, estrogenic activity is reduced and endometrial atrophy leads to amenorrhea.
• Cessation of ovarian activity and a fall in the estrogen cause a rebound increase in the secretion of FSH and LH by the anterior pituitary gland. • The FSH level may rise as much as 50-fold and LH 3-4 fold. • With further advancing years, gonadotropin activity of the pituitary gland also ceases, and a fall in FSH level eventually occurs. • There is 50% reduction in androgen production and in estrogen at menopause.
HORMONE LEVELS IN MENOPAUSE
PERIMENOPAUSE • Menopausal transition, or ‘perimenopause’, is a defined period of time beginning with the onset of irregular menstrual cycles until the last menstrual period. It is a period of 3–4 years before menopause. • This period is associated with declining estrogen levels.
INVESTIGATIONS FOR MENOPAUSE • History of various symptoms. • General examination includes blood pressure recording, weight measurement. • Blood sugar, lipid profile, ECG. • Mammography, pelvic ultrasound. • Bone density study. DEXA is the test used. • Oestrogen (E2) and FSH levels to decide on the need of HRT. • Endometrial biopsy in women on HRT.
POSTMENOPAUSAL SYMPTOMS • Hot flushes • Headache • Mood swings • Insomnia • Difficulty in concentration • Mental confusion • Depression • Stress incontinence • Urge incontinence • Osteoporotic symptoms • Irritability • Tiredness • Dyspareunia
VASOMOTOR SYMPTOMS • Vasomotor symptoms affect up to 75% of peri-menopausal women and hot flushes and sweating are the most common and most noticeable symptoms for women to seek care for. • Hot flushes are the waves of vasodilation affecting the face and the neck and these last for 2–5 min each. These are followed by severe sweating.
• Several of these flushes occur in a day, but are more severe during the night, and can disturb sleep. • Mental depression due to disturbed sleep therefore cause irritability and lack of concentration. • Palpitation and anginal pains may even be felt.
TREATMENT • Natural estrogens are used for short duration of time as 3 to 6 months. • Oral Premarin (E1-natural equine-conjugated estrogen) in the dose of 0.625 mg daily, increasing to 1.25 mg if necessary, ethinyl estradiol 0.01 mg, micronized estrogen (1-2 mg) or Evalon 1-2 mg are effective.
• Progesterone such as Duphaston (medroxyprogesterone) 10 mg for 10-12 days each month should be added to prevent endometrial hyperplasia and carcinoma caused by estrogen. • Combined estrogen and progesterone is given to avoid endometrial hyperplasia and carcinoma in the form of tablet like Femoston (1mg+5mg) is available.
OTHER DRUGS • Agents that decrease central noradrenergic tone, such as clonidine, relieve hot flushes. • Clonidine may be used orally (0.1-0.2 mg/day) or as a weekly transdermal patch (0.1 mg/day). Potential side effects include orthostatic hypotension and drowsiness. • Gabapentin is a non-hormonal anticonvulsant that reduces hot flushes by 50% if given in a dose of 900-2400 mg daily.
UROGENITAL ATROPHY • Urogenital atrophy results in vaginal dryness and pruritus, dyspareunia, dysuria, and urinary urgency. • The stress incontinence is caused by poor vascularity and tone of the internal urinary sphincter. • Prolapse of genital tract and stress incontinence of urine and feces are mostly menopausal related.
• Dyspareunia, urethral syndrome and senile vaginitis respond well to local estrogen cream, which is preferred to oral therapy. • Estriol base cream is applied every day for 10-12 days each month for a period of 3-6 months until the symptoms disappear. • Estring (vaginal ring) releases 5-10 mcg estrogen and is 90% effective over a period of 3 months.
OSTEOPOROSIS • It is an incipient slowly progressing skeletal disorder characterized by microarchitectural deterioration of bone mass resulting in increased fragility and predilection to fracture in the absence of significant trauma. • Osteoporosis is defined as a condition in which there is a fall in bone mass exceeding 2.5 standard deviations (SD) below the mean for young adults. • It is important to consider bone mineral density screening for high-risk women.
• Musculoskeletal symptoms characterized by backache, fractures on minimal trauma, decreased height, and mobility are common due to osteoporosis. • Estrogen deficiency is the dominating factor contributing to osteoporosis in women. • Additional contributing factors such as calcium and vitamin D deficiency also need consideration.
TREATMENT • Drug therapies for the prevention and treatment of osteoporosis are principally anti-resorptive drugs that reduce bone loss and anabolic agents that stimulate new bone formation. • Raloxifene, a nonsteroidal compound, is a selective estrogen receptor modulator (SERM), which reduces the risk of fracture by 50%, especially vertebra by increasing BMD by 2- 3%.
• Bisphosphonates such as Alendronate (5 mg daily or 35 mg weekly) and Risedronate (5 mg daily or 35 mg once a month) reduce bone resorption through the inhibition of osteoclastic activity.
• Bisphosphonates should not be given with calcium, because its absorption is reduced. • Calcium should be taken in the morning and alendronate swallowed (not chewed) in the afternoon, on an empty stomach with a glass of water in the upright position. This reduces the esophageal irritation. • Milk and antacid can reduce gastric irritation. • After 60 years, osteoporosis should be managed with bisphosphonates.
• Zoledronic acid is used therapeutically once a year as intravenous infusion of 4 mg over 15 min, but osteonecrosis of the jaw and visual disturbances are the major side effects. • Once a month oral Ibandronate (150mg) is made available which improves bone density. by 5-10%.
• Calcitonin is a peptide produced by thyroid C cells. It inhibits osteoclast activity and inhibits bone resorption. It is given as a nasal spray at a single dose daily for 3 months. It reduces the incidence of fracture by 30%. • Teriparatide is the recombinant formation of parathyroid hormone. About 20 mcg once-daily subcutaneous injection decreases vertebral fracture.
CARDIOVASCULAR DISEASES • Estrogen is cardioprotective by maintaining a high level of high density lipoprotein (HDL) and lowering the low density lipoprotein (LDL) and triglycerides. • Estrogen deficiency therefore can cause atherosclerosis, ischemic heart disease and myocardial infarction. • Estrogen prevents atherosclerosis through its antioxidant property.
• Oral Premarin (E1-natural equine-conjugated estrogen) in the dose of 0.625 mg daily, increasing to 1.25 mg if necessary, ethinyl estradiol 0.01 mg, micronized estrogen (1-2 mg) or Evalon 1-2 mg are effective. • Raloxifene (SERM) causes 10% reduction in total cholesterol and LDL and raises HDL level. It does not raise the level of triglycerides. It is therefore cardioprotective in long term.
DEPRESSION • Studies of mood during menopause have generally revealed an increased risk of depression during perimenopausal phase than in postmenopausal years. • Depression during perimenopause is likely due to fluctuating and declining estrogen levels in part.
• Estrogen increases the effects of serotonin and norepinephrine by decreasing monoamine oxidase (MAO) activity in the CNS, hindering the breakdown of serotonin and norepinephrine. • In addition, estrogen increases serotonin synthesis, upregulates 5-HT1 receptors, and downregulates 5-HT2 receptors. Estrogen also increases norepinephrine activity in the brain.
TREATMENT • SSRIs are the antidepressants most commonly used in the treatment of perimenopausal depression. • SSRIs are thought to be generally safe and effective. The onset of action is 4–6 weeks. • Several common adverse effects such as gastrointestinal effects (nausea, diarrhoea, and anorexia), excessive sweating, headache, jitteriness, dizziness, sedation and insomnia
• For mild depression, hormone replacement therapy (HRT) alone may be appropriate. Estrogen (0.45–0.625 mg) QD, medroxyprogesterone (1.5- 5 mg) QD. • Mild Tranquillizers - Venlafaxine 30–150 mg daily, Paroxetine 10–20 mg daily, Gabapentin 300 mg three times a day.
SLEEP DISTURBANCES • Insomnia occurs in 40–50% of women during the menopausal transition. • Women with insomnia are more likely than others to report problems such as anxiety, stress, tension, and depressive symptoms. • Sleep disturbances during menopause have been associated with estrogen deficiency or elevated LH levels during late menopause produce poor sleep quality through a thermoregulatory mechanism, resulting in high core body temperatures.
• Rates of a sleep apnea increase with age, theories include a relationship to postmenopausal weight gain or to decreased progesterone levels because progesterone stimulates respiration. • In addition to undergoing changes in estrogen and progesterone levels, postmenopausal women experience a decline in melatonin and growth hormone levels, both of which have effects on sleep.
USES OF HRT • Short term - Hot flushes Vasomotor symptoms Dyspareunia Urethral syndrome • Long term - Osteoporosis Cardiovascular Alzheimer’s disease
RISKS OF HRT • Endometrial cancer • Breast cancer • Ovarian cancer • Thromboembolism • Lipid profile dysfunction • Gall stones, liver dysfunction
HRT AND BREAST CARCINOMA • The risk of breast cancer is not increased up to 3 years of HRT and 5 years of estrogen alone replacement therapy. • Lower risk is seen with use of Progesterone in HRT. • HRT can cause recurrence of breast cancer and is therefore contraindicated in a woman who has been treated for breast cancer. • HRT increases the density of breast tissue and impede screening programme of mammography subsequently.
HRT AND ENDOMETRIAL CARCINOMA • Estrogen Replacement Therapy can cause well-differentiated carcinoma. • The risk of cancer with ERT is dose and duration dependent. • Minimum of 12 days of progesterone added to ERT reduces the risk of endometrial cancer to 2%. • Combined estrogen and progesterone provides a better protection against endometrial cancer.
CONCLUSION OF HRT • Not every menopausal woman needs HRT. • A symptomatic woman due to estrogen deficiency requires HRT for 3–6 months. The duration and route of HRT depend upon the purpose for which the therapy is prescribed. • Total duration of prophylactic therapy beyond 8–10 years has not proved beneficial, but side effects may harm the woman.
• The benefit of therapy should be balanced against the risks of breast and endometrial cancers and venous thromboembolism.
REFERENCES • Howkins J, Bourne G, editors. Shaw's Textbook of Gynaecology. 16th ed. New Delhi: Elsevier; 2014. • Brunton LL, Knollmann BC, editors. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill Education; 2018. • Dalal PK, Agarwal M. Postmenopausal syndrome. Indian J Psychiatry. 2015 Jul;57(Suppl 2):S222-32. doi: 10.4103/0019-5545.161483. PMID: 26330639; PMCID: PMC4539866.
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