Thursday, February 22, 2024

Menopause

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.

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