Gynecology Topic 16. Perimenopause

I. Definitions and Etiology

Definitions

• Menopause: permanent cessation of menstruation due to loss of ovarian follicular function.
• Diagnosis: retrospective, after 12 months of amenorrhea without another cause.
• Age: usually 45-55 years; average about 51 years.
• Perimenopause / climacteric: transition with declining ovarian function and menstrual irregularity, including the first year after menopause.
• Mean duration of perimenopause: about 4 years.

Etiology and hormonal changes

• Natural menopause: progressive depletion of ovarian follicles → decreased estrogen and inhibin → loss of negative feedback → increased FSH/LH.
• Hormone pattern: decreased estrogen, progesterone and inhibin; increased FSH most important.
• Perimenopause: fluctuating estrogen + frequent anovulation → irregular bleeding, breast tenderness and variable symptoms.
• Postmenopause: small estrogen amounts come mainly from peripheral aromatization of adrenal androgens in adipose tissue.

Premature / Iatrogenic Menopause

• Primary ovarian insufficiency / premature menopause: primary hypogonadism with menopause-like ovarian dysfunction before age 40.
• Causes: genetic, e.g. Turner syndrome; autoimmune; idiopathic.
• Iatrogenic/artificial menopause: chemotherapy, radiotherapy, bilateral oophorectomy.
• Clinical importance: HRT is usually indicated if no contraindication, often until average natural menopause age.

II. Clinical Features

Menstrual and vasomotor symptoms

• Menstrual change: irregular cycles, oligomenorrhea → amenorrhea.
• Vasomotor symptoms: hot flashes, night sweats, palpitations.
• Night sweats → insomnia → fatigue, irritability, poor concentration.

Genitourinary Syndrome of Menopause

• GSM: estrogen-deficiency symptoms/signs of vulva, vagina, urethra and bladder.
• Mechanism: low estrogen → thin dry mucosa + less Lactobacillus + higher vaginal pH → irritation and infection tendency.
• Symptoms: vaginal dryness, burning, itching, dyspareunia, postcoital spotting.
• Urinary symptoms: recurrent UTI, urgency/frequency, stress or urge incontinence.
• Pelvic support: pelvic floor weakening and tissue atrophy may contribute to pelvic organ prolapse.

Psychological and long-term effects

• Mood/cognition: irritability, mood swings, depressive symptoms, poor concentration, fatigue, memory complaints, loss of libido.
• Skin/connective tissue: collagen loss → skin thinning and loss of elasticity.
• Bone: decreased estrogen → decreased BMD → osteopenia/osteoporosis → fragility fracture risk.
• Cardiovascular/metabolic: dyslipidemia, increased LDL tendency → increased cardiovascular risk with age.

III. Diagnosis and Screening

Diagnosis

• Typical woman > 45 years: diagnosis is clinical after 12 months amenorrhea + typical symptoms.
• Always exclude pregnancy when amenorrhea is possible.
• Hormone tests: increased FSH most important, increased LH, decreased estradiol; useful in early/unclear cases.
• Pelvic examination: vulvovaginal atrophy supports GSM/menopause.
• Ultrasound: small ovaries/no follicles may support ovarian inactivity, but is not required in typical menopause.

Postmenopausal Bleeding

• Any bleeding after established menopause is abnormal until proven otherwise.
• Rule out: endometrial cancer/hyperplasia, cervical disease, atrophy, polyps, anticoagulants/HRT effect.
• Evaluation: pelvic exam → transvaginal US endometrial thickness and/or endometrial sampling according to risk and findings.

Assessment of long-term consequences

• Bone health: DEXA/DXA scan; especially age >= 65 or earlier if increased fracture risk.
• T-score: normal >= -1.0; osteopenia -1.0 to -2.5; osteoporosis <= -2.5; severe osteoporosis = osteoporosis + fragility fracture.
• Cardiovascular risk: lipid profile, blood pressure, diabetes and smoking assessment.

IV. Treatment

Lifestyle and local measures

• Treat bothersome symptoms, premature menopause, or high-risk consequences; not every menopausal woman needs drugs.
• Exercise: regular aerobic + weight-bearing/resistance training → bone, cardiovascular and mood benefit.
• Diet/weight: healthy diet, weight control, calcium and vitamin D supplementation when intake is insufficient.
• Smoking cessation and alcohol moderation → lower cardiovascular, cancer and osteoporosis risk.
• GSM: vaginal lubricants/moisturizers; pelvic floor exercises and bladder retraining for urinary/prolapse symptoms.

Hormone Replacement Therapy

• HRT / menopausal hormone therapy: most effective treatment for vasomotor symptoms; also improves GSM and increases BMD/reduces bone loss.
• Use principle: individualized risk-benefit discussion, lowest effective dose, shortest necessary duration; reassess regularly.
• Intact uterus: estrogen + progestin → progestin protects endometrium from hyperplasia/cancer.
• Post-hysterectomy: estrogen-only systemic therapy may be used.
• Local vaginal estrogen: topical option for GSM with low systemic exposure.
• Risks: DVT/PE, stroke, MI/CAD risk in older or high-risk women, breast cancer with combined therapy, gallbladder disease; unopposed systemic estrogen increases endometrial cancer risk if uterus present.

Contraindications to Systemic HRT

• Absolute/major: breast cancer, endometrial cancer unless specialist-approved, unexplained vaginal bleeding.
• Thromboembolic/cardiovascular: previous/current VTE, thrombophilia, stroke/TIA, MI or coronary heart disease.
• Other: active liver disease, pregnancy.
• Relative caution: gallbladder disease, smoking, migraine, uncontrolled cardiovascular risk, older age or long time since menopause.

Other pharmacologic treatment

• Vasomotor symptoms: SSRI/SNRI, e.g. paroxetine or venlafaxine; gabapentin; clonidine.
• Osteoporosis: bisphosphonates, e.g. alendronate/risedronate; SERM raloxifene; denosumab.
• Baseline bone support: calcium/vitamin D, weight-bearing exercise, fall-risk reduction.