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 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.