Menopause is the permanent cessation of menstruation (diagnosed after 12 months of amenorrhea) and is a normal part of the aging process. Perimenopause, sometimes called the menopausal transition, is characterized by gradually decreasing ovarian function resulting in less frequent menstruation and decreased production of female sex hormones until menstruation ceases altogether (usually between 45 and 56 years of age). Induced menopause (due to surgery and chemotherapy) leads to a swift decline in hormones, with menopause occurring earlier and more rapidly compared to physiological menopause. While menopause is defined as an absence of menstruation, it also leads to multiple other physiological changes because of the decline in sex hormones, leading to significant vasomotor symptoms, changes to the genitourinary tract, and neuropsychiatric symptoms (e.g., mood swings, sleep disturbance). In individuals with a characteristic history (e.g., the typical age of menopause with vasomotor symptoms and amenorrhea), a diagnosis of perimenopause or menopause can be made clinically. Diagnostic tests are reserved for individuals with premature menopause (i.e., before the age of 40 years) or if the clinical history requires the exclusion of alternative diagnoses. Nonpharmacological interventions are recommended for mild symptoms. Pharmacological therapy is used for moderate to severe symptoms that impair quality of life and for patients with premature, early, or induced menopause who are at increased risk for .
The female reproductive period comprises the following phases: 
- Premenopause: begins with menarche and ends with the onset of perimenopause
- Perimenopause (also called the menopausal transition): the length of time from the first occurrence of irregular menstruation cycles ; to 12 months after the final menstrual period (FMP) 
Menopause: the date of an individual's FMP
- Retroactively determined after 12 months of complete amenorrhea 
- Onset: usually from 45–56 years of age (average is 51 years of age); earlier average age in smokers 
- Physiological menopause is the normal age-related loss of ovarian function with no other identified cause 
- Postmenopause: the time after the FMP; the first 12 months are called early postmenopause. 
Physiology of menopause
|Underlying physiology of menopause symptoms |
|Menstrual irregularities and amenorrhea || |
|Vasomotor symptoms |
|Genitourinary symptoms |
The onset and intensity of symptoms depend on the phase of menopause and vary greatly between individuals. Symptoms begin during perimenopause and typically peak during the first 1–2 years of postmenopause. 
|Clinical features of menopause |
|Vasomotor symptoms of menopause (VMS)|
|Genitourinary syndrome of menopause) (GSM) || |
|Neuropsychiatric symptoms |
|Other symptoms |
In the US, more intense and longer-lasting vasomotor symptoms are reported for Black individuals than individuals of other racial or ethnic groups. 
In menopausal individuals, estrogen production mainly results from the conversion of adrenal androgens by peripheral aromatase in adipose tissue. The onset of menopause may occur later in individuals with obesity, who have additional estrogen from adipose stores.  ; Menopausal HAVOCS: Hot flashes/Heat intolerance, Atrophy of Vagina, Osteoporosis, Coronary artery disease, Sleep impairment.
Subtypes and variants
Induced menopause 
Induced menopause is the permanent loss of ovarian function as a result of medical interventions.
- Iatrogenic ovarian ablation (e.g., due to chemotherapy, radiation)
- Surgical menopause: menopause resulting from the removal of both ovaries (i.e., bilateral oophorectomy)
Clinical features 
- hormone levels. may be more pronounced because of the rapid drop in
- surgical menopause. are more severe and frequent in
- Hormone therapy if patients are below the average age of physiological menopause (∼ 51 years of age). 
- See also “Treatment of menopause.”
Premature menopause 
- Induced menopause
- Primary ovarian insufficiency; (POI): occurs in 1% of women; may be idiopathic 
- Patients may also present with infertility, or menstrual cycles that do not resume after stopping hormonal contraception. 
- May not be required if the underlying cause is known (e.g., induced menopause)
- If the cause is unknown, are recommended.
- Additional workup for POI (e.g., karyotyping) may be required.
- Hormonal therapy is recommended to reduce:
- Consider oral contraceptive use in patients with no . 
- Continue systemic HRT (unless contraindicated) until at least the average age of physiological menopause (∼ 51 years of age). 
- See also “Treatment of menopause.”
Early menopause 
- The occurrence of physiological menopause between 40 and 45 years of age with no other identified cause 
- Affects 5% of women 
- Clinical features and diagnostics are the same as for older patients.
- Systemic HRT is usually recommended to reduce risks associated with early menopause, e.g.: 
Smoking is associated with earlier onset of menopause. 
General principles 
- In individuals ≥ 40 years of age, perimenopause and menopause are diagnosed clinically.
- A pelvic examination is usually performed to confirm GSM or evaluate for other causes. 
- Diagnostic testing is reserved for:
- Premature menopause
- Patients with an unreliable menstrual cycle history 
- Suspected differential diagnoses of menopause and perimenopause 
Supportive studies to confirm menopause 
These studies are typically determined by a specialist; there is significant controversy regarding which tests are appropriate. 
- FSH: ↑↑; ; however, levels widely fluctuate during perimenopause 
- Estradiol: ↓ 
- Rarely tested for as not routinely recommended: ↓ progesterone; , ↓ inhibin B, and ↓ antimüllerian hormone 
Studies to exclude 
- pregnancy as a cause of amenorrhea: to rule out 
- Prolactin: elevated in hyperprolactinemia
- LH: elevated in POI
- TSH: Both hypothyroidism and hyperthyroidism can cause menstrual irregularities.
- Tests for testosterone, dehydroepiandrosterone sulfate (DHEA-S), 17-hydroxyprogesterone (17-OHP) :
- Transvaginal ultrasound +/- if is suspected 
Individuals with hyperthyroidism and menopause have similar symptoms. Maintain a low threshold for checking serum TSH in individuals with heat intolerance, irregular menstruation, and disturbed sleep. 
These studies are not routinely part of the menopause workup but if performed, findings may show characteristic changes.
- Lipid panel: ↑ total cholesterol and ↓ HDL are common during menopause
- DXA scan: recommended for all women aged ≥ 65 years and younger women with additional risk factors (see “Screening for osteoporosis”) 
|Differential diagnoses of common menopause symptoms|
|Hot flashes or night sweats |
|Genitourinary symptoms || |
|Neuropsychiatric symptoms|| |
The differential diagnoses listed here are not exhaustive.
The information in this section is on the management of physiological menopause in individuals aged > 45 years. For the management of premature menopause, early menopause, and induced menopause, see “Subtypes and variants.”
- Determine the severity of symptoms and their impact on the patient's quality of life.
- All symptomatic patients: Initiate .
- For patients with moderate to severe symptoms, consider adding . 
- For perimenopausal individuals, discuss .
- Screen for and treat associated conditions and/or complications and provide appropriate preventive care.
Questionnaires, e.g., the menopause-specific quality of life scale, may help to determine the severity of symptoms and guide treatment.
For further information on indications, contraindications, and dosages, see “Pharmacological therapy for menopause.”
|Overview of menopause management |
|Symptom-specific nonpharmacological interventions for menopause||Symptom-specific pharmacological therapy for menopause|
|Vasomotor symptoms of menopause |
|Genitourinary syndrome of menopause |
|Menstrual symptoms|| |
|Psychological symptoms |
Evidence does not support the use of alternative medical therapies for menopause, e.g., soy, black cohosh, omega-3 supplementation, and acupuncture. 
Systemic hormone replacement therapy (HRT) 
- HRT should be titrated to the lowest effective dose. 
- Reevaluate patients on HRT yearly. 
- Short-term use (< 5 years) may be preferred to reduce the risk of adverse effects (e.g., breast cancer). 
- Premature menopause, induced menopause, or early menopause
Moderate to severe vasomotor symptoms affecting quality of life if both criteria are met : 
- < 60 years of age
- Menopausal for < 10 years
- Moderate to severe genitourinary symptoms of menopause 
- Prevention of osteoporosis in postmenopausal individuals (controversial) 
- Systemic estrogen hormonal options include oral and transdermal preparations.
- Transdermal preparations may have a lower risk of VTE and cardiovascular disease. 
- Patients without a uterus: estrogen-only HRT
Patients with a uterus: estrogen-containing HRT combined with an endometrial protection agent
- Combined estrogen-progestin preparations, e.g.:
- Estrogen PLUS an SERM, e.g., conjugated estrogen PLUS bazedoxifene 
- Estrogen-only HRT plus a levonorgestrel-releasing IUD (off-label) 
Unopposed systemic estrogen can increase the risk of endometrial hyperplasia and endometrial cancer. In individuals with a uterus, add an agent that protects the endometrium (e.g., progestins, bazedoxifene). 
Some clinicians prescribe compounded bioidentical hormones; however, these are not FDA-approved and are not recommended by any major societies as there is no evidence they are superior to standard HRT. 
- Unexplained vaginal bleeding
- Estrogen-sensitive cancer (e.g., endometrial or breast cancer)
- Chronic liver disease
- Current or prior DVT, stroke, thromboembolic disease, or thrombophilia
- Coronary artery disease or myocardial infarction
Adverse effects 
- Serious: thromboembolic events, estrogen-sensitive cancer (e.g., endometrial cancer, breast cancer) 
- Common: mood swings, headache, gastrointestinal upset (e.g., nausea, bloating), weight gain, retained fluid, breast pain, breakthrough bleeding
- Other: stress urinary incontinence, gallbladder disease
Vaginal hormone therapy 
Vaginal hormone therapy is indicated for moderate to severe .
- Estrogen-based intravaginal treatments ; 
- Intravaginal DHEA, i.e., vaginal prasterone 
- Undiagnosed vaginal bleeding
- Estrogen-sensitive cancers (e.g., endometrial or breast cancer) 
- History of a prior thromboembolic event 
- Liver disease 
Adverse effects 
- Risk of estrogen-sensitive cancers and thromboembolic events; however, risk is lower than for systemic HRT 
- Vaginal discharge, candidiasis, or bleeding
As low-dose vaginal estrogen is generally not associated with endometrial hyperplasia, additional progestin is typically not added for endometrial protection. However, patients should be advised to immediately report any vaginal bleeding. 
Nonhormonal therapy 
- Alternative treatment for patients who decline, or have contraindications to, HRT
- Second-line treatment for moderate to severe menopausal symptoms
- Ovulation can still occur until the FMP. 
- Discuss the risks and benefits of continuing hormonal contraception until menopause is confirmed. 
- Options: any form of contraception, unless contraindicated 
- Continue contraception until pregnancy is unlikely, e.g.: 
- Once individuals are older than the average age of menopause (i.e., 51 years of age) 
- Patients using menstrual cycles for 12 months  : no occurrence of
- Patients using hormonal contraception: if FSH levels taken ≥ 2 weeks after discontinuing oral contraceptives indicate menopause (unreliable) 
- : Decreased circulating estrogen impairs bone formation. 
- Postmenopausal bleeding: any vaginal bleeding that occurs after menopause ; 
- Unplanned pregnancy: Ovulation, though infrequent, still occurs during perimenopause (see also “Contraception during perimenopause”. 
We list the most important complications. The selection is not exhaustive.
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