Practice Essentials
Menopause is diagnosed after 12 months of amenorrhea.
Hormonal changes and clinical symptoms occur over a period leading up to and immediately following menopause; this period is frequently termed the climacteric or perimenopause but is increasingly referred to as the menopausal transition.
See Menopause: Changes and Challenges, a Critical Images slideshow, to help identify comorbidities and diseases in the postmenopausal population.
Clinical effects
During the menopausal transition, physiologic changes in responsiveness to gonadotropins and their secretions occur, with wide variations in hormone levels. Women often experience a range of symptoms, including the following:
Hot flashes or flushes (most common)
Insomnia
Weight gain and bloating
Mood changes
Irregular menses
Mastodynia
Depression
Headache
The temporal pattern of symptoms is as follows:
Symptoms may begin up to 6 years before the final menstrual period and continue for a variable number of years after the final menstrual period
As the postmenopause years progress, with an accompanying loss of ovarian response to gonadotropins, associated affective symptoms of menopause also decline
On pelvic examination, the effects of gonadal hormone depletion (which may be noted before menopause in some women) are as follows:
With loss of estrogen, the vaginal epithelium becomes redder as the epithelial layer thins and the small capillaries below the surface become more visible
Later, as the vaginal epithelium further atrophies, the surface becomes pale because of a reduced number of capillaries
Rugation diminishes, and the vaginal wall becomes smooth
The menopausal ovary diminishes in size and is no longer palpable during gynecologic examination
The uterus becomes smaller
Fibroids, if present, become less symptomatic, sometimes shrinking to the point where they can no longer be palpated on manual pelvic examination
In older women, a general loss of pelvic muscle tone occurs, sometimes manifested as prolapse of reproductive or urinary tract organs
Urogenital effects of diminished hormone levels are as follows:
A decrease in urine pH leading to a change in bacterial flora may result in pruritus and a malodorous discharge
Vaginal changes often result in insertional dyspareunia
Endometriosis and adenomyosis are alleviated
Atrophic cystitis, when present, can mimic a urinary tract infection
Menopause markers
Laboratory markers of menopause include the following:
An increase in serum follicle-stimulating hormone (FSH) and decreases in estradiol and inhibin are the major endocrine changes that occur during the transition to menopause
FSH levels are higher than luteinizing hormone (LH) levels, and both rise to even higher values than those seen in the surge during the menstrual cycle
The FSH rise precedes the LH rise; FSH is the diagnostic marker for ovarian failure, while LH is not necessary to make the diagnosis
The large cyclical variation of estradiol and estrone observed during the menstrual years ceases, and fluctuation in levels is small and inconsequential, with the mean value being considerably lower
No specific changes in thyroid function related to menopause have been found
Endometrial changes
Endometrial biopsy can show a range of endometrial appearances, from mildly proliferate to atrophic
No secretory changes are observed after menopause, because no ovulation occurs and therefore no corpus luteum forms to produce progesterone
Endometrial hyperplasia is a sign of hyperstimulation by estrogen from either endogenous sources or replacement therapy and may be a precursor of endometrial cancer
Endometrial hyperplasia can also be suggested by ultrasonographic findings (ie, endometrial thickness >5 mm), which are useful for excluding hyperplasia and cancer of the endometrium in postmenopausal women
Osteoporosis
Bone loss accelerates in the late menopausal transition and continues for the first few years after menopause.
Postmenopausal women and elderly women should be treated early and on a long-term basis unless a contraindication to such treatment exists.
Current treatment options for preventing fractures among postmenopausal women with osteoporosis include the following:
Bisphosphonates (alendronate, etidronate, ibandronate, risedronate, zoledronic acid)
Selective estrogen receptor modulators (SERMs; eg, raloxifene)
Calcium
Vitamin D
Calcitonin
Monoclonal antibodies
Hormonal medications
Estrogen therapy (considered a second-line therapy for osteoporosis
)
Replacement therapy
The main reasons for treating symptoms of the menopausal transition and actual menopause are as follows:
To provide relief of vasomotor symptoms
To reduce the risk of unwanted pregnancy
To avoid the irregularity of menstrual cycles
To preserve bone
To lower the risk of disease
To improve quality of life
Disease risk
In the Women’s Health Initiative (WHI), greater safety and possible benefit from hormone or estrogen therapy for women in their 50s, with potential harm for older women, were observed with respect to the following
:
Coronary artery disease (CAD)
Total myocardial infarction
Colorectal cancer
Total mortality
Global index of chronic diseases
Although immediate use of hormone or estrogen therapy in the early postmenopausal time may reduce the risk of CAD, the WHI clearly showed that women more than 9 years post menopause should not be started on hormone therapy or estrogen therapy for CAD prevention.
Administration routes for hormone therapy are as follows:
Oral
Transdermal
Topical
Vaginal route cream, ring, or tablet for vaginal symptoms
Contraindications for estrogen therapy include the following:
Undiagnosed vaginal bleeding
Severe liver disease
Pregnancy
Venous thrombosis
Personal history of breast cancer
Well-differentiated and early endometrial cancer, once treatment for the malignancy is complete, is no longer an absolute contraindication. Progestins alone may relieve symptoms if the patient is unable to tolerate estrogens.
Nonhormonal therapy
In June 2013, the FDA approved paroxetine mesylate (Brisdelle) as the first nonhormonal therapy for vasomotor symptoms (VMS) (hot flashes) associated with menopause.