Menopausal Syndrome

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Menopausal Syndrome : 

Menopausal Syndrome

Introduction : 

Introduction Permanent cessation of menstruation due to loss of ovarian follicular function Diagnosed retrospectively after 12 months of amenorrhea Average age is 51 years

Perimenopause : 

Perimenopause

Introduction : 

Introduction Time period preceding menopause when fertility decreases, menstrual irregularities increase Onset of perimenopause precedes the final menses by 2 to 8 years Smoking accelerates the menopausal transition by 2 years

Physiology : 

Physiology Ovarian mass and fertility decline sharply after the age of 35 years Depletion of primary follicles Rise in FSH levels due to Altered folliculogenesis Reduced inhibin secretion

Physiology : 

Physiology Consistently high FSH and low Estradiol levels in Menopause Perimenopause – irregularly irregular hormone levels

Physiology : 

Physiology Anovulatory cycles produce Hyperestrogenic / Hypoprogestagenic environment and increases the incidence of Endometrial Hyperplasia or Carcinoma Uterine polyps Leiomyoma

Physiology : 

Physiology With transition into menopause Marked fall of Estradiol levels Relative preservation of estrone levels due to Peripheral aromatization of adrenal and ovarian androgens Increase in FSH levels more than those of Luteinizing Hormone

Investigations : 

Investigations History General examination: BP, Weight, Breast, Hirsuitism Pelvic examination; Pap smear Blood sugar, lipid profile Mammography, pelvic ultrasound (Ovarian size, Endometrial Thickness) Bone Mineral Density Oestradiol level and FSH – to decide on need for HRT

Diagnostic Tests : 

Diagnostic Tests Low FSH in the early follicular phase of the menstrual cycle is inconsistent with a diagnosis of perimenopause FSH and fertility < 20, 20 to 30 mIU/ml and  30 on day 3 of the cycle means Good, Fair or Poor chance of pregnancy

Symptoms : 

Symptoms Menopausal transition causes Hot flushes Night sweats Irregular bleeding Vaginal dryness Sleep disturbances

Symptoms : 

Symptoms Mood swings Depression Impaired memory or concentration Somatic symptoms Urinary incontinence Sexual dysfunction

Treatment : 

Treatment Irregular or Heavy bleeding - Low dose combined oral contraceptives (20 µgm of Ethinyl Estradiol + 1 mg Norethindrone Acetate) daily for 21 days each month eliminates vasomotor symptoms and regularizes cycles Protects against ovarian cancer / endometrial cancers Increases bone density Contraceptive effect

Contraindications : 

Contraindications Oral contraceptives Cigarette smoking Liver Disease Thromboembolism / Cardiovascular disease Breast Cancer Unexplained vaginal bleeding

Treatment : 

Treatment Progestin only formulations 0.35 mg Norethindrone daily Medroxy progesterone injections (Dipoprovera 150 mg) IM every 3 months In people who smoke or have increased Cardiovascular risk

Treatment : 

Treatment Non hormonal Strategies to reduce menstrual flow Non steroidal anti-inflammatory Mefenamic acid Initial dose of 500 mg at start of menses Then 250 mg QID for 2 to 3 days Endometrial Ablation

Investigations : 

Investigations For menorrhagia rule out uterine disorders with Transvaginal ultrasound with saline enhancement for detecting Leiomyomata or polyps Endometrial aspiration for identifying Hyperplastic changes

Transition : 

Transition Transition to Menopause 1 year absence of spontaneous menses indicates ovulation cessation Age of final menses among relatives is a reliable guide

Hormone Therapy : 

Hormone Therapy Hormone therapy in Menopause and Post Menopausal cases The largest trial by Women’s Health Initiative (WHI)

Hormone Therapy : 

Hormone Therapy Definite Benefits Definite improvement in symptoms of menopause Definite increase in bone mineral density and decrease in fracture risk in cases of Osteoporosis

Hormone Therapy : 

Hormone Therapy Definite Risks In Endometrial Cancer, there is definite increase in risk with estrogen alone; no increase in risk with estrogen progestin In venous Thromboembolism, there is definite increase in risk In Breast Cancer, there is increase in risk with long-term use ( 5 years) of estrogen progestin In Gall bladder disease, there is definite increase in risk

Hormone Therapy : 

Hormone Therapy Uncertain risks and Benefits Increased risk in Coronary Heart Disease, Stroke, Ovarian cancer Decreased risk in Colorectal Cancer, Diabetes Mellitus, Cognitive Dysfunction

Definite Benefits : 

Definite Benefits Estrogen therapy is highly effective for controlling vasomotor and genitourinary symptoms

Definite Benefits : 

Definite Benefits Alternative approaches Antidepressants (Venlafaxine 75 to 150 mg/dl) Gabapentin 300 to 900 mg/dl Clonidine 0.1 to 0.2 mg/dl Vitamin E – 400 to 800 IU/dl Soy-based products or other phytoestrogens Vaginal estrogen for Genitourinary symptoms

Bone Density : 

Bone Density By reducing bone turnover and resorption rates, estrogen slows the aging related bone loss which is experienced by most postmenopausal women

Estrogen Therapy : 

Estrogen Therapy Postmenopausal estrogen therapy with / without a progestogen, rapidly increases bone mineral density at Spine by 4 to 6% Hip by 2 to 3 %

Fractures : 

Fractures 50 to 80% - lower risk of vertebral fracture 25 to 30% - lower risk of hip, wrist and other peripheral fractures

Treatment : 

Treatment Bisphosphonates Alendronate 10 mg/day or 70 mg once per week Risedronate 5 mg/day or 35 once per week Ibandronate 2.5 mg/day or 150 mg once per week or 3 mg every 3 months IV Selective Estrogen Receptor Modulator (SERM) Ralofexine 60 mg/day It increases bone mass density & decrease fracture rates

Treatment : 

Treatment Parathyroid Hormone Teriparatide 20 µgm / day (s/c) Increased physical activity Adequate Calcium (1000 to 1500 mg/day through diet) Vitamin D (400 to 800 IU/day)

Definite Risks : 

Definite Risks Endometrial Cancer (With Estrogen alone) Venous Thromboembolism Breast Cancer (With Estrogen-Progestin) Gallbladder disease

Endometrial Cancer (With Estrogen alone) : 

Endometrial Cancer (With Estrogen alone) Tripling of endometrial cancer risk among short term (1 to 5 years) users of unopposed estrogen Nearly ten fold risk among users (> 10 years)

Venous Thromboembolism : 

Venous Thromboembolism Doubling of venous thromboembolism risk in postmenopausal women with estrogen use WHI indicate a two fold increase in risk of venous and pulmonary thromboembolism associated with estrogen-progestin One third increase in this risk with estrogen only therapy

Breast Cancer (With Estrogen-Progestin) : 

Breast Cancer (With Estrogen-Progestin) Increased risk of breast cancer among estrogen users Short term use (< 5 years) of post menopausal HT did not appreciably elevate breast cancer incidence Long term use (> 5 years was associated with a 35% increase in risk Combined estrogen – progestin regimens appear to increase breast cancer risk more than estrogen alone In the Heart and Estrogen / Progestin Replacement Study, 4 years of combination therapy, 27% increase in breast cancer risk.

Gallbladder Disease : 

Gallbladder Disease Two to three fold increased risk of gallstones or cholecystectomy among postmenopausal women taking oral estrogen WHI – Estrogen – Progestin 67% and Estrogen alone 93% (Greater risk) for cholecystectomy Transdermal hormonal therapy may not increase

Probable or Uncertain Risks and Benefits : 

Probable or Uncertain Risks and Benefits Coronary Heart Disease / Stroke Colorectal Cancer Cognitive Decline and Dementia Ovarian Cancer and Other Disorders

Coronary Heart Disease / Stroke : 

Coronary Heart Disease / Stroke Estrogen use leads to 35 - 50% reduction in CHD Exogenous estrogen lowers plasma low-density lipoprotein (LDL) cholesterol Raises high-density lipoprotein (HDL) cholesterol levels by 10 to 15%

Coronary Heart Disease / Stroke : 

Administration of estrogen favourably affects Lipoprotein (a) levels LDL oxidation Endothelial vascular function Fibrinogen Plasminogen activator inhibitor - 1 Coronary Heart Disease / Stroke

Coronary Heart Disease / Stroke : 

Administration of estrogen unfavourably affects Other biomarkers of cardiovascular risk Boosts triglyceride levels Promotes coagulation via Factor VII, Prothrombin fragments 1 & 2, and fibrinopeptide A elevations Raises levels of the inflammatory marker C-reactive protein Coronary Heart Disease / Stroke

Coronary Heart Disease / Stroke : 

Coronary Heart Disease / Stroke Lower risk of CHD in women who choose to start Hormone therapy within 4 years of menopause than non users Estrogen / Combined Estrogen – Progestin in women with pre-existing cardiovascular disease has not confirmed the benefits

Colorectal cancer : 

Colorectal cancer Hormone therapy reduces risks of colon and rectal cancer In WHI, Estrogen – Progestin 44% reduction in colorectal cancer No benefit with estrogen only

Cognitive Decline and Dementia : 

Cognitive Decline and Dementia Post menopausal Hormone Therapy is associated with a 34% decreased risk of dementia (Meta-analysis) WHI – no benefit of estrogen or estrogen – progestin therapy on the progression of mild to moderate Alzheimer’s disease

Ovarian Cancer and other disorders : 

Ovarian Cancer and other disorders Hormone therapy increases the risk of ovarian cancer Reduces the risk of Type 2 Diabetes Mellitus WHI supports these findings

Post Menopausal Hormone Therapy : 

Post Menopausal Hormone Therapy Approach to the patient Potential side effects Vaginal bleeding Contraindications to Hormone Therapy

Indications for Hormone Therapy : 

Indications for Hormone Therapy Moderate to severe menopausal symptoms Vasomotor Urogenital symptoms in the absence of vasomotor can be treated with vaginal estrogen

Contraindications to Hormone Therapy : 

Contraindications to Hormone Therapy Unexplained vaginal bleeding Active liver disease Venous Thromboembolism History of endometrial / breast cancer History of CHD, stroke, TIA or DM

Contraindications to Hormone Therapy : 

Relative Contraindications Hypertriglyceridemia (> 400 mg /dL) Active gallbladder disease Transdermal estrogen may be an option for cases of Relative Contraindication Contraindications to Hormone Therapy

Contraindications to Hormone Therapy : 

A woman who suffers an acute coronary event or stroke while on Hormone Therapy should stop therapy immediately Contraindications to Hormone Therapy

Short Term use of Hormone Therapy : 

< 5 years For relief of menopausal symptoms If contraindicated Antidepressants Gabapentin Clonidine Soy / black cohosh Genitourinary symptoms Intravaginal estrogen cream / device Short Term use of Hormone Therapy

Long Term use of Hormone Therapy : 

Long Term use of Hormone Therapy  5 years (especially estrogen– progestogen) Reasonable candidates Persistent severe vasomotor symptoms Increased risk of Osteoporosis No personal / family history of breast cancer

Long Term use of Hormone Therapy : 

Poor candidates are women with Elevated cardiovascular risk Increased risk of breast cancer Low risk of Osteoporosis Long Term use of Hormone Therapy

Slide 53: 

Thank You

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