Problems associated with HRT

The major side effects of estrogen are nausea, edema, breast tenderness and stomach upset (dyspepsia); a two-fold increase in gall bladder disease, proliferation of endometrial tissue, migraine and steepening of the corneal curvature with consequent intolerance of contact lenses.

The major side effects of progestogen administration are depressive moods, mood swings, fatigue, edema, breast tenderness, insomnia, weight gain and irregular menstrual bleeding.

Each episode of irregular bleeding needs investigation to exclude endometrial cancer. If a woman has regular but heavy bleeding endometrial thickness should be assessed. A repeat ultrasound scan is sometimes necessary after two to three cycles.

A number of clinical conditions can be aggravated by estrogen treatment - chronic liver disease, neuro-ophthalmological vascular disease, porphyria, endometriosis, undiagnosed vaginal bleeding and otosclerosis.

Whether estrogen should be given to women after surgery for endometrial cancer and the length of time that should be allowed to elapse before estrogen replacement is instigated is still a matter for debate. Combined estrogen-progestogen therapy may therefore be preferable for women who have undergone hysterectomy and bilateral oophorectomy because of endometriosis. In obese women, conventional estrogen replacement may be associated with bleeding problems. Since peripheral conversion of androgens to estrogens in fat tissue is increased in these women, it is advisable to reduce the dose of estrogen so that the circulating levels achieved are similar to those in women with normal weight receiving standard replacement doses of estradiol.

Estrogens may also have adverse effects in some women with seizure disorders, familial hypertriglyceridaemia and migrainous headache.

Currently, absolute contraindications to estrogen replacement are limited to undiagnosed vaginal bleeding, acute liver disease, acute vascular thrombosis or embolism, recent breast cancer and recent endometrial cancer. The first two conditions are short-term problems and after their resolution estrogen may be prescribed. A non-oral route of estrogen is preferable in those with liver disease.

Relative contraindications include a past history of superficial vein thrombosis or hepatitis, in both of which non oral estrogen is safe.