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Menopausal Hormone Replacement Therapy

Practice Essentials

Hormone therapy (HT) involves the administration of synthetic estrogen and progestogen to replace a woman’s depleting hormone levels and thus alleviate menopausal symptoms. However, HT has been linked to various risks; debate regarding its risk-benefit ratio continues.

The image below depicts the stages and nomenclature of normal reproductive aging in women.

Stages/nomenclature of normal reproductive aging i

Stages/nomenclature of normal reproductive aging in women.

See Menopause: Changes and Challenges, a Critical Images slideshow, to help identify comorbidities and diseases in the postmenopausal population.

Signs and symptoms

The spectrum and intensity of perimenopausal and menopausal symptoms vary greatly due to the effect of decreased circulating levels of estrogen on various organ systems.

The most common presentation of menopause (60% of postmenopausal women) is hypothalamically mediated vasomotor instability leading to hot flashes (hot flushes), sweating, and palpitations. Other common presenting symptoms include the following:

Irregular menstrual cycles

Urogenital symptoms: Vaginal dryness, soreness, superficial dyspareunia, urinary frequency and urgency

Psychological symptoms: Mood changes, insomnia, depression, anxiety

Menopausal effects

Menopause has the following physiologic effects:

Vasomotor system: Vasomotor instability

Urogenital system: Atrophy and thinning of the mucosal lining of the urethra, urinary bladder, vagina, and vulva; loss of vaginal elasticity and distensibility; reduced vaginal secretions; degeneration of subepithelial vasculature and the supporting subcutaneous connective tissue

Bone metabolism: Progressive bone loss

Cardiac function: Increased susceptibility to heart disease

Forms of HT

HT can be prescribed as local (creams, pessaries, rings) or systemic therapy (oral drugs, transdermal patches and gels, implants). Hormonal products available in such preparations may contain the following ingredients:

Estrogen alone

Combined estrogen and progestogen

Selective estrogen receptor modulator (SERM)

Gonadomimetics, such as tibolone, which contain estrogen, progestogen, and an androgen

The estrogens most commonly prescribed are conjugated estrogens that may be equine (CEE) or synthetic, micronized 17β estradiol, and ethinyl estradiol. The progestins that are used commonly are medroxyprogesterone acetate (MPA) and norethindrone acetate.

The various schedules of hormone therapy include the following:

Estrogen taken daily

Cyclic or sequential regimens: Progestogen is added for 10-14 days every 4 weeks

Continuous combined regimens: Estrogen and progestogen are taken daily

HT indications, contraindications, and adverse effects/risks

Indications

Indications for hormone therapy can be symptomatic or preventive. However, the application of HT to prevent sequelae of menopause is controversial, although some consensus has been reached regarding the use of HT to relieve symptoms.

The following are common clinical indications for prescribing HT:

To relieve vasomotor symptoms

To improve urogenital symptoms (long-term therapy is required)

To prevent osteoporosis

Contraindications

No absolute contraindications of HT have been established. However, relative contraindications exist in certain clinical situations, such as patients with the following findings:

A history of breast cancer*

A history of endometrial cancer*

Porphyria

Severe active liver disease

Hypertriglyceridemia

Thromboembolic disorders

Undiagnosed vaginal bleeding

Endometriosis

Fibroids

* Note that many clinicians do not prescribe HT for women with a previous history of breast or endometrial cancer.

Adverse effects and risks

Possible transient adverse effects are as follows:

Nausea

Bloating, weight gain (equivocal finding), fluid retention

Mood swings (associated with use of relatively androgenic progestogens)

Breakthrough bleeding

Breast tenderness

Potential risks of HT in postmenopausal women include the following:

Breast cancer: Use of combined HT; study results inconsistent, but emerging consensus of slightly increased risk for breast cancer similar to that associated with natural late menopause—comes into effect after at least 5 years of continuous HT

Endometrial cancer
and uterine hyperplasia and cancer: Use of HT based on unopposed estrogen

Thromboembolism: Use of combined or estrogen-only HT

Biliary pathology: Use of estrogen only or combined estrogen/progestogen HT

Evaluation for hormone therapy

All candidates for HT should be thoroughly evaluated with a detailed history and complete physical examination for a proper diagnosis and identification of any contraindications.

Baseline laboratory and imaging studies before administering HT include the following:

Hemography

Urinalysis

Fasting lipid profile

Blood sugar levels

Serum estradiol levels: In women who will be prescribed an implant and in those whose symptoms persist despite use of an adequate dose of a patch or gel

Serum follicle-stimulating hormone (FSH) levels: To monitor women taking oral preparations for symptomatic control, especially those with premature menopause

Ultrasonography: To measure endometrial thickness and ovarian volume

Electrocardiography

Papanicolaou test

Mammography: Performed once every 2-3 years and annually after the age of 50 years

Endometrial sampling is not required in routine practice. However, the presence of abnormal bleeding before or during HT should prompt consideration of ultrasonography to check endometrial thickness (cutoff, < 4 mm), followed by outpatient Pipelle sampling and hysteroscopy. In women with a tight cervix, formal hysteroscopy and dilation and curettage under general anesthesia are advised.

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