Menopause- Causes, Symptoms, Diagnosis, Treatment and Ongoing care
- Natural menopause: Permanent cessation of menstrual periods for at least 12 consecutive months in a nonpregnant woman ≥45 years old
- Resulting from ovarian follicular depletion
- Not associated with a pathologic etiology
- Perimenopause: From the onset of menstrual changes through the 1st year of menopause (average length of perimenopause is 4–5 years)
- Postmenopause: Usually accounts for >1/3 of a woman’s life
- Premature menopause: Menopause occurring before age 40; may be associated with sex chromosome abnormalities
- Average age of perimenopause onset is 47.5 years.
- Mean age of menopause onset is between 51–52 years.
In the US, 1.3 million women reach menopause annually.
- Sex chromosome abnormalities (e.g., Turner syndrome)
- Age of maternal menopause
Goal is not to prevent menopause, but to retard development of osteoporosis related to menopause:
- Weight-bearing exercise
- Avoid smoking
- Avoid excessive alcohol and caffeine intake
- Maintain healthy weight
- Calcium intake 1,200–1,500 mg/d beginning in adolescence
- Adequate vitamin D (800–1,200 IU daily)
Normal physiologic process
- As women age, the number of ovarian follicles decreases: Ovarian production of estrogen and inhibin decreases, and leuteinizing (LH) and follicle-stimulating hormone (FSH) production increases.
- Without estrogen, failure of endometrial development occurs and menstrual cycles become irregular, then cease.
- Symptoms directly or indirectly due to decrease in estrogen
- Surgical: Removal of functioning ovaries due to disease or incidental to hysterectomy
- Treatment of endometriosis
- Treatment of breast cancer with antiestrogens (which is reversible)
- May occur after cancer chemotherapy (permanent or reversible)
- Cessation of menses:
- Generally preceded by a period of irregular cycles and/or diminished bleeding
- Vasomotor symptoms: Hot flashes and sweating, often at night (30–80%)
- First manifestation of menopause
- Usually last ∼3–4 minutes, occur at unpredictable intervals
- Frequency usually declines with time
- Mood changes (8–38%), anxiety, depression
- Sleep disorders (35–60%)
- Lengthening of latent phase
- Less time spent asleep
- Urogenital atrophy:
- Atrophic vaginitis causes vaginal dryness (17–30%), itch, dyspareunia, and possible sexual dysfunction.
- Urethral atrophy causes urgency, frequency, dysuria, stress incontinence.
- Atrophy of paravaginal tissues that support bladder and rectum can lead to urocele, rectocele, uterine prolapse.
- Osteopenia and osteoporosis
- Change in intensity and severity of migraines
- Skin thinning, hair loss, hirsutism, brittle nails
Vaginal bleeding in a postmenopausal women is abnormal; endometrial cancer must be ruled out.
- Decrease in breast size and change in breast texture
- External, speculum, and bimanual pelvic exams: Atrophic vaginal mucosa (urogenital atrophy)
Diagnostic Tests & Interpretation
Initial lab tests
- Generally none required; patient’s age and symptoms readily establish the diagnosis
- If laboratory confirmation is desired:
- Elevated serum FSH level >30 mIU/mL indicates ovarian failure.
- Symptoms may precede changes in lab parameters.
- Drugs that may alter lab results: Estrogens, androgens, oral contraceptive pills (OCPs)
- LH has no role in diagnosing menopause.
Annual mammography is recommended for menopausal women (upper age limit for discontinuation remains uncertain).
Follow-Up & Special Considerations
- Brain magnetic resonance imaging (MRI) if pituitary tumor suspected
- Abnormal vaginal bleeding in a postmenopausal patient should be evaluated by transvaginal ultrasound (TVUS) and/or endometrial biopsy:
- If endometrial stripe is <5 mm on TVUS, endometrial carcinoma is unlikely.
- Bone mineral density (BMD) testing with dual energy x-ray absorptiometry (DEXA) scan in postmenopausal women <65 years with additional risk factors (not otherwise indicated at onset of menopause):
- Previous history of fractures, low body weight, cigarette smoking, family history of fractures should be tested, if osteoporosis is a concern (not usually indicated at onset of menopause).
- Abnormal BMD and DEXA scan results:
- T-score on DEXA of 1.0–2.5 = osteopenia
- T-score >2.5 = osteoporosis
- Defer to femoral neck T-score value over spine T-score
- Z-score measures age-matched mean bone density (not clinically useful)
- Polycystic ovarian syndrome
- Pituitary adenoma
- Anorexia nervosa causing amenorrhea
- Hypothalamic dysfunction
- Asherman syndrome
- Obstruction of uterine outflow tract
- Sheehan syndrome
Treatment choice depends on severity of symptoms.
Hormone therapy (HT) (1):
- The primary indication for HT is the treatment of moderate-to-severe vasomotor symptoms. Combination estrogen-progestin therapy is effective treatment for these symptoms, and other menopausal symptoms (sleep disorders, urogenital atrophy). It is also useful for prevention of osteoporotic fractures, colorectal cancer, and may help with mood symptoms (2,3)[A].
- Current recommendations for HT suggest use for a limited duration (i.e., few years) in the treatment of menopausal symptoms in women who are near menopause and do not have a history of and are not at high risk for coronary artery disease, stroke, breast cancer, or thromboembolism. If these risk factors are present, or if the woman is asymptomatic, alternative treatments to prevent bone loss should be considered.
- If HT is selected, estrogen should be given in combination with progestin for women with an intact uterus. Depending on duration of use, unopposed estrogen carries a 2.0–6.7-fold higher risk of endometrial cancer. Most data available are for continuous treatment (as opposed to cyclical) with combined conjugated equine estrogen (CEE) 0.625 mg and medroxyprogesterone acetate 2.5 mg. However, considerable evidence supports the use of low-dose HT, which is associated with 50% lower rates of irregular bleeding. Low dose = 0.3 or 0.45 mg/d of CEE (4)[A].
- The Women’s Health Initiative (WHI) study, in 2002, done in women without established coronary heart disease (CHD), found those treated with combination estrogen-progestin therapy had an increased relative risk of invasive breast cancer, coronary heart disease, stroke, and pulmonary embolism at 5 years of use (3,5)[A]. This risk of breast cancer was found to be independent of mammography screening frequency (1)[B]. Put another way, for every 100 women treated with HT for 5 years, 1 will have a serious adverse event.
- The Heart and Estrogen/Progestin Replacement study (HERS), done in women with established CHD, demonstrated improvements in the lipid profiles of women on HT, but the overall risk of vascular mortality did not decline.
- There is an increased risk of ovarian cancer in women who take HT. 1 out of every 8,300 women who take hormone replacement therapy each year has been shown to suffer from ovarian cancer (6)[B].
- Higher doses of estrogen can cause hypercoagulability, breast tenderness, gallbladder disease, and hypertension (HTN).
- Contraindications to HT:
- Estrogen-dependent malignancies
- Unexplained uterine bleeding
- History of thromboembolism or stroke
- Coronary artery disease
- Active liver disease
- For osteoporosis:
- Screening and treating women at risk for osteoporosis can help prevent fractures (7)[A].
- Bisphosphonates inhibit osteoclast action and resorption of bone:
- Alendronate (Fosamax): Treatment dose: 70 mg/week or 10 mg/d. Prevention dose: 35 mg/week or 5 mg/d.
- Risedronate (Actonel): 35 mg once a week or 5 mg/d. Same dose for prevention and treatment.
- Zoledronic acid (Reclast or Zometa): 5 mg IV annually. Same dose for prevention and treatment.
- Ibandronate (Boniva): 2.5 mg/d or 150 mg/month. Same dose for prevention and treatment.
- Selective estrogen receptor modulators (SERMs) selectively inhibit or stimulate estrogen-like action in various tissues. The SERM used for the treatment of osteoporosis is:
- Raloxifene (Evista): 60 mg/d for prevention and treatment; because raloxifene is a less potent antiresorptive drug than alendronate, risedronate, or estrogen, it is best suited for the prevention or treatment of mild osteoporosis (8)[A].
- The EFFECT trial demonstrated that raloxifene decreased the risk of vertebral fracture, but failed to demonstrate a decrease in the risk of extravertebral fractures.
- Raloxifene should be used primarily in postmenopausal women with predominantly spinal osteoporosis (8,9)[A].
- Calcium: 1,200–1,500 mg elemental calcium p.o. daily
- Vitamin D: 800 IU–1,200 IU p.o. daily
- For atrophic vaginitis:
- Topical estrogen therapy (ET): Conjugated estrogens (Premarin cream); best for local therapy of atrophic vaginitis. ET reverses vaginal atrophy, enhances blood flow, reduces pH and urinary tract infections (UTIs). ET is applied to vaginal mucosa as needed. Data are insufficient to recommend annual endometrial surveillance in women using ET with no vaginal bleeding. ET should be continued as long as distressing symptoms remain. Women with a history of hormone-dependent cancer should consult with an oncologist prior to initiation of therapy (10)[B].
For vasomotor symptoms:
- Nonhormonal treatments may be helpful for women who wish to or need to avoid HT (e.g., breast CA):
- Antidepressants venlafaxine (37.5–75 mg/d), paroxetine (10–20 mg/d), or fluoxetine (20 mg/d) are options that have been shown to result in 1 fewer hot flash a day.
- Gabapentin (300–900 mg/d) has been shown to have some effect in reducing vasomotor symptoms by up to 2 hot flashes per day (11)[A].
- Clonidine may be used to treat mild hot flashes, although it is less effective than antidepressants or gabapentin. Initial oral dose is 0.05 mg b.i.d.; some women may require 0.1 mg b.i.d.
- All trials of 2nd-line therapies have been of short duration, i.e., a few months (9,11)[A].
Complementary and Alternative Medicine
Trials of nonprescribed therapies are difficult to interpret due to variability of components and doses:
- Soy isoflavone showed mixed effect in placebo-controlled trials in reduction of hot flashes.
- Red clover, black cohosh, reflexology, aerobic, and magnet therapy showed no impact on hot flashes when compared to placebo.
- Small clinical trials of evening primrose, dong quai, ginseng, and wild yam do not support their use for relief of hot flashes.
- DEXA scan is indicated at age 65 for all women
- Pap smear and mammography per standard health maintenance guidelines
Calcium and vitamin D supplements as above
Encourage lifestyle modifications:
- Smoking cessation
- Weight-bearing exercise
- Avoid excess alcohol and caffeine
- Address cardiovascular risk factor modification
- Ultimate disappearance of vasomotor symptoms; usually takes several years
- Osteoporosis: Possible fractures of the hip, vertebrae, and wrists
- Osteoporosis: Bone loss occurs at a rate of 0.3–0.5% per year beginning in the 4th decade, but at menopause, women have accelerated bone loss up to 3–5% per year for 5–7 years. HT is clearly protective against bone loss. Smoking cessation, physical activity, and calcium supplementation should be encouraged to decrease risk of osteoporosis.
- Increased risk of coronary artery disease due to loss of protective benefits of estrogen on lipid profile and endothelium
1. Chlebowski RT, Kuller LH, Prentice RL, et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med. 2009;360:573–87.
2. Nelson HD. Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review. JAMA. 2004;291:1610–20.
3. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–33.
4. Lobo RA, et al. Should symptomatic menopausal women be offered hormone therapy? Med Gen Med. 2006;8(3):40–58.
5. Rossouw JE, Prentice RL, Manson JE, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297:1465–77.
6. Mørch LS, Løkkegaard E, Andreasen AH, et al. Hormone therapy and ovarian cancer. JAMA. 2009;302:298–305.
7. USPSTF. http://www.ahrq.gov/clinic/epcsums/osteoporosis.pdf.
8. Sambrook PN, Geusens P, Ribot C, et al. Alendronate produces greater effects than raloxifene on bone density and bone turnover in postmenopausal women with low bone density: results of EFFECT (Efficacy of FOSAMAX versus EVISTA Comparison Trial) International. J Intern Med. 2004;255:503–11.
9. Riggs BL, Hartmann LC. Selective estrogen-receptor modulators – mechanisms of action and application to clinical practice. N Engl J Med. 2003;348:618–29.
10. North American Menopause Society. The role of local vaginal estrogen for treatment of vaginal atrophy in postmenopausal women. Menopause. 2007;14(3):357–69.
11. National Guideline Clearinghouse. Menopause. http://www.guideline.gov.
- V49.81 Asymptomatic postmenopausal status (age-related) (natural)
- 256.31 Premature menopause
- 237123000 Normal menopause (finding)
- 373717006 Premature menopause (finding)
- Menopause is usually diagnosed by history alone (if laboratory confirmation of menopause is desired, then elevated serum FSH level >30 mIU/mL indicates ovarian failure). LH has no role in diagnosing menopause.
- Current recommendations are that HT be used short-term for relief of moderate-to-severe vasomotor symptoms, but not in the longer term for prevention of cardiovascular disease.