Menopause: Pathogenesis and Clinical Findings
Perimenopause/Menopausal Transition: Phase preceding last menstrual period in which the first symptoms may occur. Many clinical findings of menopause can occur in perimenopause.
1-2 million primordial follicles
first appear in fetal ovaries in the end of the first trimester of the mother’s pregnancy
Typically beginning in adolescence, puberty triggers physiological and anatomical changes
Menarche (commencement of menstrual cycles) See relevant slide: Menstrual Cycle Physiology: Ovarian Cycle – Brief Overview
Each cycle involves ovulation, during which an oocyte is released from the ovary’s dominant follicle into the Fallopian tube
Some non-dominant follicles degenerate in a process known as atresia
Menstrual cycle stops
Menopause marks 1 year since last menstrual cycle
↓ Fluid transudatio
n from blood vessels of vaginal wall
↓ Vaginal lubrication
Vaginal tissue becomes thinner and more easily irritated
Over time, fewer
follicles remain in the ovary
Some cycles become anovulatory (no oocyte is released from ovary)
↓ Ovulation causes prevents thickening of the endometrial lining
↓ regularity and frequency of periods
Ovaries eventually stop releasing oocytes
↑ Oxidative stress- induced apoptosis of dermal fibroblasts
Remaining non-dominant follicles become less sensitive to LH and FSH
Since follicular cells are responsible for estrogen production, less follicles result in reduced estrogen production
↓ Expression of serotonin receptors in the CNS
↓ LDL receptor expression and ↑HMG- CoA reductase activity
↓ Regulation of the production and clearance of LDL
↑ LDL Cholesterol levels
Author: Sunawer Aujla Reviewers: Ashar Memon Yan Yu* * MD at time of publication
↓ Serotonin activity
↓ Density of
↓ Healthy vaginal flora
↑ pH of vaginal fluid
↑ Spread of bacteria otherwise unable to survive in low pH environment
Recurrent urinary tract infections
↓ Calcitonin
↑ Sensitivity of bone mass to Parathyroid Hormone
↑ Activation of osteoclasts
Mechanism is likely
multifactorial and the subjective symptoms of menopause may contribute
5HT receptors in
thermoregulatory region of hypothalamus
↑ Inhibition of sexual responses initiated in prefrontal cortex
↓ Libido
↓ Collagen, elastin, and hyaluronic acid
↓ Proliferation of smooth muscle fibers
↓ Inhibition of osteoclasts
Narrower thermoregulatory zone
Injury to epithelial tissue in multiple areas of the body
Atrophy of bladder and urethra epithelium
Urinary incontinence
More bone resorption than formation
See relevant slide: Osteoporosis: Pathogenesis and risk factors
Sometimes, for unknown reasons, core body temperature increases above upper threshold of narrowed thermoregulatory zone
Hot Flashes
Sudden, temporary onset of body warmth, flushing, and sweating
Sometimes, for unknown reasons, core body temperature decreases below lower threshold of narrowed thermoregulatory zone
Sudden, temporary onset of shivering, tingling, cold feeling
Atrophy of vaginal epithelium
Pain during sexual intercourse
↓ Integrity of of blood vessels
↑ Risk for cardiovascular disease
Genitourinary Syndrome of Menopause
Sign/Symptom/Lab Finding
Published June 7, 2023 on