I-27. Postmenopause

閉経後（ポストメノポーズ）

Hormonal Changes

Loss of estradiol negative feedback → FSH rises then stabilizes high; LH rises, slightly falls, stays high.
Follicle count = 0 → very low inhibin B, estradiol, AMH.
Early postmenopause resembles late transition but without bleeding. Late symptoms = long-term estrogen-deficiency consequences.

Metabolic Changes

↑Obesity prevalence (mood disorders, inactivity); ↓BMR.
Body composition: lean mass lost (↓estradiol → muscle atrophy); fat accumulates (↓estradiol activates lipoprotein lipase, inhibits hormone-sensitive lipase).
Fat redistributes to central/visceral: ↑leptin/resistin, ↓ghrelin/adiponectin → insulin resistance → dyslipidemia (atherogenic) + chronic inflammation.

Lipid Changes (estrogen deficiency)

↑Total cholesterol, LDL, TAG; ↓HDL (estrogen normally inhibits lipogenesis/cholesterol synthesis, ↑LDL receptors/excretion).
→ Atherogenic profile; non-alcoholic fatty liver disease.

Cardiovascular Changes

Reproductive-age CV protection ends → CVD ~50% of postmenopausal mortality.
Early: ↑BP, subclinical vascular abnormalities (arterial stiffness, intima-media thickening, ↑coronary calcium score, impaired flow-mediated vasodilation). Later: sharp ↑coronary disease/stroke.
Accelerated atherosclerosis from estrogen deficiency:
- Indirect: visceral fat, dyslipidemia, insulin resistance, chronic inflammation.
- Direct: ↓NO, ↑endothelin, local vascular RAAS activation → oxidative stress, vascular inflammation, cell proliferation, endothelial dysfunction.

Osteoporosis

Loss of mineralized matrix from trabecular bone (age-related affects compact bone); fastest in first 5 years post-menopause.
Symptoms: pathological fractures (vertebrae, femoral neck, wrist), bone/back pain, ↓height (vertebral flattening).
Mechanism (estrogen loss → ↑resorption): osteoblasts ↓OPG + ↑RANKL → ↑osteoclast maturation/survival; ↓TGF-β → ↓osteoclast apoptosis; ↑osteoblast PTH responsiveness. Aging adds ↓Ca²⁺ absorption + vitamin D deficiency.

Urogenital Atrophy

↓Collagen → thinner/weaker vaginal walls + lax ligaments → uterine prolapse, incontinence.
↓Blood flow → ↓glycogen → ↓lactobacillus → ↑vaginal pH → infections; ↓secretion → epithelial atrophy, dryness.
Symptoms: vaginal dryness/painful intercourse, recurrent UTI, itching, pelvic anatomy changes.

CNS

Estrogen normally supports prefrontal cortex/striatum/hippocampus (learning, memory, decisions, language) and is anti-inflammatory/neurotrophic.
Deficiency → forgetfulness, learning difficulty, ↓linguistic skills, ↑susceptibility to neurodegeneration/ischemia.

Other & Treatment

Skin: thins, loses elasticity, dry (↓keratinocyte/collagen support). Breast: glandular tissue → adipose (sagging).
Treatment: target the consequences — hormone replacement therapy (topical for urogenital atrophy, systemic for hot flashes) + symptomatic treatment.

一問一答

▶What are the hormonal changes of postmenopause?

Loss of estradiol feedback → FSH rises then stabilizes high and LH rises (then slightly falls, stays high); follicle count is 0, so inhibin B, estradiol, and AMH are very low.

▶How does early postmenopause differ from the late transition?

It resembles the late transition hormonally but occurs without any bleeding; late symptoms reflect long-term estrogen-deficiency consequences.

▶How does body composition change after menopause?

Lean/muscle mass is lost (↓estradiol → muscle atrophy) and fat accumulates (↓estradiol activates lipoprotein lipase, inhibits hormone-sensitive lipase); BMR falls.

▶Why does central/visceral fat accumulation after menopause cause insulin resistance?

Visceral fat raises leptin/resistin and lowers ghrelin/adiponectin → insulin resistance → atherogenic dyslipidemia and chronic inflammation.

▶What lipid changes result from postmenopausal estrogen deficiency?

↑Total cholesterol, LDL, and TAG with ↓HDL (estrogen normally inhibits lipogenesis/cholesterol synthesis and ↑LDL receptors) → atherogenic profile and NAFLD.

▶Why does cardiovascular risk rise sharply after menopause?

Loss of reproductive-age estrogen protection (CVD becomes ~50% of postmenopausal mortality), via indirect (visceral fat, dyslipidemia, insulin resistance, inflammation) and direct vascular effects.

▶What are the direct vascular effects of estrogen deficiency?

↓NO, ↑endothelin, and local vascular RAAS activation → oxidative stress, vascular inflammation, cell proliferation, and endothelial dysfunction.

▶What early subclinical vascular abnormalities appear in postmenopause?

Rising BP, arterial stiffness, intima-media thickening, increased coronary calcium score, and impaired flow-mediated vasodilation — later progressing to overt coronary disease/stroke.

▶Which bone type is preferentially lost in postmenopausal osteoporosis, and when is loss fastest?

Trabecular bone is lost first (age-related loss affects compact bone), with the fastest loss in the first 5 years after menopause.

▶What is the mechanism of postmenopausal osteoporosis?

Estrogen loss → osteoblasts ↓OPG and ↑RANKL (↑osteoclast maturation/survival), ↓TGF-β (↓osteoclast apoptosis), and ↑osteoblast PTH responsiveness; aging adds ↓Ca²⁺ absorption + vitamin D deficiency.

▶What are the symptoms of postmenopausal osteoporosis?

Pathological fractures (vertebrae, femoral neck, wrist), bone/back pain, and loss of height from vertebral flattening.

▶Why does urogenital atrophy develop after menopause?

↓Collagen thins/weakens vaginal walls and laxens ligaments (→ prolapse, incontinence); ↓blood flow → ↓glycogen → ↓lactobacilli → ↑vaginal pH (infections) and epithelial atrophy/dryness.

▶What are the symptoms of postmenopausal urogenital atrophy?

Vaginal dryness, painful intercourse, recurrent UTIs, itching, and changes in pelvic anatomy.

▶How does estrogen deficiency affect the CNS after menopause?

Loss of estrogen support to prefrontal cortex/striatum/hippocampus (and its anti-inflammatory/neurotrophic effects) → forgetfulness, learning difficulty, ↓linguistic skills, and ↑susceptibility to neurodegeneration/ischemia.

▶What skin and breast changes occur after menopause?

Skin thins, loses elasticity, and becomes dry (↓keratinocyte/collagen support); breast glandular tissue is replaced by adipose tissue (sagging).

▶What is the general treatment approach to postmenopausal symptoms?

Target the consequences: hormone replacement therapy (topical for urogenital atrophy, systemic for hot flashes) plus symptomatic treatment.

▶Why do FSH and LH stay persistently high after menopause?

With no follicles producing estradiol/inhibin, negative feedback on the pituitary is lost, so gonadotropins remain elevated.

▶Why does obesity prevalence increase after menopause?

Declining BMR, reduced physical activity, mood disorders, and estrogen-driven shifts in fat metabolism favor fat gain.

▶How does estrogen normally protect the lipid profile?

It inhibits lipogenesis/cholesterol synthesis and increases LDL receptors and cholesterol excretion; its loss raises LDL/TAG and lowers HDL.

▶How does postmenopausal estrogen loss accelerate atherosclerosis indirectly?

Through visceral fat accumulation, atherogenic dyslipidemia, insulin resistance, and chronic low-grade inflammation.