- Clinical science
Menopause is the time at which a woman permanently stops menstruating, usually between 45 and 55 years of age, and is diagnosed after 12 months of amenorrhea. It is preceded by the climacteric period, sometimes referred to as perimenopause or menopausal transition, which is the transition period in a woman's life from the time of full sexual maturity to the onset of menopause. The physical manifestations are caused by hormonal changes (primarily a drop in progesterone and estrogen levels) that occur during the climacteric period. Clinical features leading up to menopause include irregular menses, autonomic symptoms (e.g., hot flashes), mental symptoms (e.g., mood swings), and atrophic features (e.g., reduced breast size, vaginal atrophy). Menopausal transition is a natural phase of the aging process in females, and as such does not usually warrant treatment. However, treatment is warranted in the case of severe symptoms or early onset menopause. The choice of treatment is decided on a case-by-case basis and includes conservative methods, hormone replacement therapy, and non-hormonal therapy. Menopause occurring before the age of 40 is considered premature. A common cause of premature menopause is ovarian insufficiency. The diagnosis is confirmed by increased FSH levels occurring after more than three months of amenorrhea in a woman under the age of 40. Treatment involves hormone replacement therapy.
- Definition: the time period from the first instance of climacteric symptoms caused by fluctuating hormonal levels to one year after menopause
- Duration: The average length of perimenopause is 4 years.
- Definition: the time period from the first occurrence of climacteric irregular menstruation cycles to the last menstrual period
- Onset: usually 45–55 years of age
- Characterized by increasingly infrequent menstruation
- Definition: time at which menstruation ceases permanently and confirmed after 12 months of amenorrhea
- Average age at menopause: ∼ 49–52 years (earlier in smokers)
- Postmenopause: : the time period beginning 12 months after the last menstrual period
Numerical depletion of ovarian follicles with age → ↓ ovarian function → ↓ estrogen and progesterone levels → loss of negative feedback to the gonadotropic hormones → ↑ GnRH levels → ↑ levels of FSH and LH in blood (hypergonadotropic hypogonadism) → ↑ frequency of anovulatory cycles → ovarian function eventually stops permanently 
In menopausal women, estrogens are mainly produced by peripheral aromatase conversion of adrenal androgens in adipose tissue. Therefore, onset of menopause might be delayed and symptoms might be milder in obese women.
The onset and intensity of symptoms is dependent on the phase of menopausal transition. 
- Menstruation: irregular menses (which gradually decrease in frequency) to complete amenorrhea
- Autonomic symptoms
- Mental symptoms
Atrophic features: result from an age-related drop in estrogen levels
- Breast tissue atrophy: breast tenderness and reduced breast size
- Vulvovaginal atrophy: atrophy of the vulva, cervix, vagina; leading to vaginal dryness, pruritus, and dyspareunia (See “.”)
- Urinary atrophy: atrophy of the urinary tract leading to urinary incontinence, dysuria, urinary frequency, urgency, and increased urinary tract infections
Menopausal HAVOCS: Hot flashes/Heat intolerance, Atrophy of Vagina, Osteoporosis, Coronary artery disease, Sleep impairment.
The onset and duration of these symptoms is widely variable. Symptoms may begin up to 6 years before menopause and continue for a number of years after the last menstrual period.
- : due to removal of ovaries (commonly after hysterectomy with bilateral salpingo-oophorectomy) 
Diagnosis is usually clinical. However, certain laboratory tests may help confirm the onset/presence of perimenopause. 
- ↓ Estrogen, ↓ progesterone, ↓ inhibin B, ↑↑ FSH
- Testosterone and prolactin levels are within normal ranges.
- Vaginal pH > 4.5
- Lipid profile: ↑ total cholesterol, ↓ HDL
Treatment is not warranted for all women approaching or undergoing menopause, as it is a normal aging process. Treatment may be considered in the following cases:
- Symptoms are severe; enough to infringe significantly on functional capacity, and hence affect quality of life.
- Premature menopause
- Surgical menopause (e.g., post-oophorectomy)
Lifestyle modifications and local medical therapy 
- For hot flashes
- Avoidance of triggers (e.g., bright lights, predictable emotional triggers)
- Environmental temperature regulation (e.g., using fans)
- For atrophic vaginal symptoms: vaginal estrogen creams, rings, or tablets (Estrogen therapy may reduce the incidence of UTIs and features of overactive bladder.)
- For impaired sleep and/or hot flashes: exercise, acupuncture, and relaxation techniques
- Prevention of
- Smoking cessation, adequate vitamin D intake, and regular weight-bearing exercise
- See “.”
- Alternative medicine therapies (like black cohosh/Cimicifuga racemosa, a phytotherapeutic with estrogen-like effects) are widely used, but the efficacy of most of these therapeutic modalities has been debated or is not yet proven. 
Hormone replacement therapy (HRT) 
- Indication: short-term treatment of menopausal symptoms
- Routes: oral, transdermal
- Cardiovascular disease: coronary heart disease, deep vein thrombosis, pulmonary embolism, stroke
- Gallbladder disease
- Stress urinary incontinence
Non-hormonal therapy is used to treat menopausal vasomotor symptoms in women who do not want to use hormonal medications or who have contraindications for HRT. 
- Definition: permanent cessation of menses before the age of 40
- Primary ovarian insufficiency
- Bilateral oophorectomy 
Smoking is associated with premature menopause.
- Definition: failure of adequate ovarian function (endocrine as well as reproductive) before the age of 40, which often leads to premature menopause
- Definition: ovarian insufficiency despite adequate gonadotropin stimulation (previously called premature ovarian failure)
- Idiopathic (90% of cases)
- Genetic disorders associated with ovarian hypoplasia, especially in women < 30 years; (e.g., Turner syndrome; , Swyer syndrome, androgen insensitivity syndrome, adrenogenital syndrome, fragile X syndrome)
- Autoimmune diseases; (e.g., autoimmune lymphocytic oophoritis, Hashimoto thyroiditis, Addison disease, type I diabetes mellitus, pernicious anemia)
- Toxins: Smoking is a major risk factor.
- Iatrogenic: radiation and/or chemotherapy, prolonged therapy, induction of multiple ovulation in infertility treatment
- Infectious diseases (e.g., measles, mumps, tuberculosis of the genital tract)
- Pathophysiology: follicular dysfunction or depletion → ↓ estrogen levels → reduced feedback inhibition of estrogen on FSH and LH → ↑ FSH and LH (usually FSH > LH)
Clinical features 
- Climacteric symptoms such as vaginal dryness, night sweats, hot flashes, dyspareunia, and irritability
- Abnormal/irregular bleeding pattern that can progress to secondary amenorrhea or permanent cessation of menstruation
- Infertility or reduced fertility (Pregnancy is possible via in vitro fertilization.)
- See “.”
- Treatment of underlying causes