Menopause and POI Overview Quiz

Overview

• Menopause: Final menstrual period, confirmed retrospectively after 1 year of amenorrhea.
• Cause: Cessation of regular ovarian function.
• Average age: 51-52 years old, with 95% of women experiencing menopause between 45 and 55.

Diagnosis

• Elevated FSH levels (over 30 IU) at least 6 weeks apart are needed for diagnosis.

Non Physiological Menopause

• Premature Ovarian Insufficiency (POI): Occurs before 40 years of age.
  • Affects approximately 1% of women under 40 and 0.1% under 30.
  • Gamete donation is the only option for conception.
  • Diagnosed after primary or secondary amenorrhea.
  • Can cause unpredictable bleeding and a small risk of pregnancy.
• Causes of POI:
  • Primary:
    • Chromosome anomalies (e.g. Turner's, Fragile X)
    • Autoimmune disease (e.g. hypothyroidism, Addison's, myasthenia gravis)
    • Enzyme deficiencies (e.g. galactosemia, 17a-hydroxylase deficiency)
  • Secondary:
    • Chemotherapy or radiotherapy
    • Infections (e.g. tuberculosis, mumps, malaria, varicella)

Iatrogenic Menopause

• Medical treatments that induce menopause:
  • GnRH agonists (e.g. buserelin, goserelin): Used for endometriosis and other gynecological problems.
    • Cause temporary menopause with rapid onset.
    • Managed with hormone therapies and add-back therapy.
• Surgical Menopause:
  • Performed to treat benign gynecological conditions (e.g. menstrual disorders, fibroids, endometriosis).
  • Bilateral salpingo-oophorectomy (BSO) is also performed prophylactically for women at high risk of inherited malignancies (e.g. breast and ovarian cancer).

Effects of Menopause by Time of Onset

• Immediate (0-5 years):
  • Vasomotor symptoms: Hot flushes, night sweats.
  • Psychological symptoms: Mood swings, anxiety, tearfulness.
  • Loss of concentration, poor memory.
  • Joint aches and pains.
  • Dry and itchy skin, hair changes.
  • Decreased sexual desire.
• Intermediate (3-10 years):
  • Vaginal dryness, soreness.
  • Dyspareunia (painful intercourse).
  • Urgency of urine.
  • Recurrent urinary tract infections.
  • Urogenital prolapse.
• Long term (>10 years):
  • Osteoporosis.
  • Cardiovascular disease.
  • Dementia.

Central Nervous System and Vasomotor Symptoms

• Vasomotor symptoms:
  • Colloquially known as "hot flushes." Night sweats are hot flushes that occur at night.
  • Thought to be caused by the loss of oestrogen's modulating effect on serotinergic receptors in the brain.
  • Result in exaggerated peripheral vasodilatory responses to minor temperature changes.
  • Occur in up to 80% of women, with less than 30% seeking help.
  • Night sweats can be highly distressing.
  • Triggers include alcohol, caffeine, and smoking.
  • Worsened by high BMI.

Psychology and Mood

• Menopause is associated with low mood, irritability, lack of energy, tiredness, and impaired quality of life.

Endometrial Effects

• Initial irregular or scanty bleeding is caused by reduced oestrogenic endometrial stimulation.
• Periods cease when the endometrium is no longer stimulated.

Lifestyle Issues

• Changes in body fat distribution: From gynecoid (breasts and hips) to android (abdominal).
• Changes in serum lipid levels: Increase in triglycerides, total cholesterol, and LDL cholesterol with a reduction in HDL cholesterol.

Management

• Diet and lifestyle:
  • Regular exercise.
  • Smoking cessation.
  • Reduced alcohol consumption.
  • Normal BMI.
  • Reduced calorie intake.
  • Benefits:
    • Fewer, less severe vasomotor symptoms.
    • Beneficial effects on bone loss.
    • Reduced incidence of breast and endometrial cancer.
    • Reduced risk of CVD.
    • Prevention of lung cancer.
    • Improved bone health.

Non-Hormonal Approaches

• Phytoestrogens: Contain isoflavones, which may reduce vasomotor symptoms, osteoporosis, cardiovascular disease, and the risk of breast and endometrial cancer.
• Biphosphonates: Pyrophosphate analogues that interfere with osteoclastic resorption (e.g., alendronate). Used to prevent and treat osteoporosis and fractures.

Hormonal Replacement Therapy (HRT)

• Types of hormones:
  • Oestrogens:
    • Risk of endometrial hyperplasia and cancer if given without progestogen.
    • Systemic oestrogen-only HRT is suitable for women who have had a hysterectomy.
  • Oestrogen with progestogen:
    • Needed to protect the endometrium in women who have not had a hysterectomy.
    • Given cyclically over a 28-day cycle.
    • Can cause regular monthly menstruation.
    • Suitable for women during the perimenopause or early postmenopausal years.
    • Can be given continuously.
  • Testosterone:
    • Traditionally given to women with sexual desire and energy level issues.
• Routes of HRT delivery:
  • Oral: Convenient and cheap, but influences lipid metabolism and coagulation through its effects on the liver.
  • Transdermal: Patches or gels applied to the skin.
    • Delivers oestradiol directly into circulation, avoiding liver and coagulation effects.
  • Vaginal tablets, rings, and creams:
    • Useful for lower genital tract symptoms.
• Progestogen can be administered via an intrauterine releasing system (IUS, Mirena®).
  • Provides contraception, controls bleeding, and offers endometrial protection for up to 5 years.

Tibilone

• Synthetic hormone preparation.

Osteoporosis Prevention and Treatment

• Non-hormonal treatments:
  • Lifestyle modification:
    • Supplementary calcium: 1-1.5 g/day
    • Weight-bearing exercise: Walking, jogging
    • Vitamin D supplementation: 1500-2000 IU/day
    • Sunlight exposure: Enhances vitamin D3 synthesis.
    • Smoking and alcohol cessation.
    • Reduced high coffee intake.
    • Reduce medications that cause bone loss (e.g. corticosteroids).
    • Nutritious diet: Balanced with calcium and protein.
    • Periodic bone density evaluation (hip).
  • Phytoestrogens: May lower the incidence of vasomotor symptoms, osteoporosis, CVD, and the risk of breast and endometrial cancer.
  • Biphosphonates: Interfere with osteoclastic resorption (e.g., alendronate).
• Hormonal treatment:
  • Oestradiol: 2mg or equivalent. Increases bone mass.
  • Combined Oestrogen with progestogen.
  • Tibilone.

Key Benefits of HRT

• Vasomotor symptoms:
  • Improved hot flushes.
  • Improved sleep patterns.
  • Improved daytime performance.
• Prevention of osteoporosis:
  • Increased bone mineral density.
  • Reduced incidence of fragility fractures.
• Other benefits:
  • Potential benefit on colon cancer incidence and mortality.
  • Lower genital tract improvement: Dryness, soreness, dyspareunia, cystitis, and occasionally dysuria.
  • CVD: Preventative effect if started early in menopause.

Contraindications and Potential Side Effects

• Absolute contraindications:
  • Suspected pregnancy.
  • Breast cancer.
  • Endometrial cancer.
  • Active liver disease.
  • Uncontrolled hypertension.
  • Current venous thromboembolism (VTE).
  • Known thrombophilia (e.g. Factor V Leiden).
  • Otosclerosis.
• Relative contraindications:
  • Unexplained abnormal bleeding.
  • Large uterine fibroids.
  • Past history of benign breast disease.
  • Unconfirmed personal or family history of VTE.
  • Chronic stable liver disease.
  • Migraine with aura.
• Side effects associated with oestrogens:
  • Breast tenderness or swelling.
  • Nausea.
  • Leg cramps.
  • Headaches.
• Side effects associated with progestogen:
  • Fluid retention.
  • Breast tenderness.
  • Headaches.
  • Mood swings.
  • Depression.
  • Acne.

Risks of HRT

• Breast cancer:
  • Background risk in the 50-59 age group is 22.5 per 1,000 women.
  • 7.5 years of HRT use may result in an additional 2-6 breast cancers.
• Cardiovascular disease and stroke:
  • Beneficial effects when given to younger women.
  • May be deleterious when given to older women.
  • Stroke incidence is higher with HRT in older women (2 additional cases per 10,000 women/year).
• Venous thromboembolism (VTE):
  • HRT doubles the risk of VTE in women over 50 (background incidence is 15-20 per 10,000).
  • Transdermal HRT may have a lesser effect on VTE incidence.