• Clinical science

Menopause

Summary

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

  • Perimenopause
    • 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.
  • Premenopause
    • 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
  • Menopause [1][2]
    • 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

Pathophysiology

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 [2]

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.

Clinical features

The onset and intensity of symptoms is dependent on the phase of menopausal transition. [2]

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.

Subtypes and variants

  • Surgical menopause: due to removal of ovaries (commonly after hysterectomy with bilateral salpingo-oophorectomy) [3]

Diagnostics

Diagnosis is usually clinical. However, certain laboratory tests may help confirm the onset/presence of perimenopause. [4][5]

FSH levels can fluctuate widely in perimenopause.

All postmenopausal women above the age of 65 should be screened for osteoporosis (i.e., using the DEXA scan to measure bone mineral density).

Hyperthyroidism and menopause present similarly. Serum TSH should be checked in all suspected perimenopausal cases with heat intolerance and disturbed sleep to determine the cause.

Treatment

Indications [5]

  • 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 [5]

  • 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 osteoporosis
    • Smoking cessation, adequate vitamin D intake, and regular weight-bearing exercise
    • See “Osteoporosis.”
  • 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. [6]

Hormone replacement therapy (HRT) [5]

Non-hormonal therapy

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. [7]

Disorders related with cessation of menstruation

Premature menopause

Smoking is associated with premature menopause.

Ovarian insufficiency

  • Definition: failure of adequate ovarian function (endocrine as well as reproductive) before the age of 40, which often leads to premature menopause

Primary ovarian insufficiency (POI) [9]

Secondary ovarian insufficiency

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  • 2. Dutta DC, Konar H. DC Dutta's Textbook of Gynecology. New Delhi, India: Jaypee Brothers Medical Publishers; 2013.
  • 3. Lobo RA, Kelsey J, Marcus R. Menopause: Biology and Pathobiology. Academic Press; 2000.
  • 4. U.S. Preventive Services Task Force. Screening for osteoporosis in postmenopausal women: Recommendations and rationale. Ann Intern Med. 2002; 137(6): pp. 526–528. pmid: 12230355.
  • 5. Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism. 2015; 100(11): pp. 3975–4011. doi: 10.1210/jc.2015-2236.
  • 6. Nedrow A, Miller J, Walker M, Nygren P, Huffman LH, Nelson HD. Complementary and Alternative Therapies for the Management of Menopause-Related Symptoms. Arch Intern Med. 2006; 166(14): p. 1453. doi: 10.1001/archinte.166.14.1453.
  • 7. DeGregorio M, Soe L, Wurz G, Kao C-J. Ospemifene for the treatment of dyspareunia associated with vulvar and vaginal atrophy: potential benefits in bone and breast. Int J Womens Health. 2013; 5: p. 605. doi: 10.2147/ijwh.s39146.
  • 8. Hendrix SL. Bilateral oophorectomy and premature menopause. Am J Med. 2005; 118(12): pp. 131–135. doi: 10.1016/j.amjmed.2005.09.056.
  • 9. American College of Obstetricians and Gynecologists. Committee Opinion Number 605: Primary Ovarian Insufficiency in Adolescents and Young Women. Obstet Gynecol. 2014; 124(1): pp. 193–7. doi: 10.1097/01.AOG.0000451757.51964.98.
  • 10. Nelson LM. Primary Ovarian Insufficiency. N Engl J Med. 2009; 360(6): pp. 606–614. doi: 10.1056/NEJMcp0808697.
  • 11. Ebrahimi M, Asbagh FA. Pathogenesis and causes of premature ovarian failure: An update. Int J Fertil Steril. 2011; 5(2): pp. 54–65. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059950/.
last updated 11/02/2020
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