Divigel Special Precautions

Before therapy is initiated, a thorough medical history should be taken. A complete gynecological examination should be performed and repeated at least once a year during therapy. Follow-up examination of the breasts and/or mammography should be carried out in accordance with current acceptance practices, modified according to the clinical needs of the individual.
Prolonged use without addition of a progestin may cause endometrial hyperplasia. Therefore, in women with an intact uterus, Divigel treatment should be combined with cyclic progestin administration. Withdrawal bleeding resembling normal menstruation will usually occur after each course of progestin. The cause of unexpected or prolonged uterine bleeding during therapy should be clarified. Atypical adenomatous hyperplasia of endometrium must be treated before entering estrogen therapy.
Development of de novo frequent severe headaches or migraine should be investigated and possible prodromal symptoms of vascular occlusion should be clarified.
The risks and benefits of treatment should be evaluated and close monitoring performed for patients with: Endometriosis. Uterine leiomyoma. Endometrial hyperplasia (simple glandular hyperplasia or hyperplasia glandularis cystica). Diseases of the cardiovascular system including cerebrovascular disorders. History of thromboembolic disease. Severe hypertension. History of (or close family history of) breast cancer. Severe disturbances of the lipid metabolism. Renal dysfunction. Systemic lupus erythematosus. Porphyria.
A reanalysis of original data from 51 epidemiological studies reported a small or moderate increase in the probability of having breast cancer diagnosed in women currently or recently using HRT. The findings may be due to an earlier diagnosis, the biological effects of HRT, or a combination of both. The probability of diagnosing breast cancer increased with duration of treatment and returned to normal in the course of 5 years after stopping HRT: breast cancers diagnosed in current or recent users of HRT are less likely to have spread outside the breast than those found in non-users.
Between the ages of 50-70 years, about 45 women in every 1000 not using HRT will have breast cancer diagnosed, the rate increasing with age. It is estimated that among those who use HRT for 5 to 15 years, depending on the age of starting and duration of treatment, the number of additional cases of breast cancer diagnosed will be of the order of 2 to 12 cases per 1000 women.
Ovarian Cancer: Ovarian cancer is much rarer than breast cancer. Epidemiological evidence from a large meta-analysis suggests a slightly increased risk in women taking oestrogen-only or combined oestrogen-progestagen HRT, which becomes apparent within 5 years of use and diminishes over time after stopping. Some other studies, including the Women's Health Initiative trial, suggest that the use of combined HRTs may be associated with a similar or slightly smaller risk.
Epidemiological studies have suggested that HRT is associated with a higher relative risk of developing venous VTE, i.e. DVT or pulmonary embolism. The studies find a 2 - 3 fold higher risk for users compared with non-users, which for healthy women amounts to one to two additional cases of VTE in 10,000 patient-years of treatment with HRT. The occurrence of such an event is more likely in the first year of HRT than later.
Generally recognised risk factors for VTE include a personal history or family history, severe obesity (Body Mass Index >30 kg/m2) and systemic lupus erythematosus (SLE). There is no consensus about the possible role of varicose veins in VTE.
Use of HRT in patients with a history of recurrent VTE or known thrombophilic states already on anticoagulant treatment require careful consideration of the benefit-risk of use of HRT (see also Contraindications).
The presence of a personal or strong family history of recurrent thromboembolism or recurrent spontaneous abortion should be investigated in order to exclude a thrombophilic predisposition. Until a definitive diagnosis has been made or anticoagulant treatment initiated, use of HRT in such patients should be viewed as contra-indicated.
The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery. As in all post-operative patients, scrupulous attention should be given to prophylactic measures to prevent VTE following surgery. Where prolonged immobilisation is liable to follow elective surgery, particularly abdominal or orthopaedic surgery to the lower limbs, consideration should be given to temporarily stopping HRT four to six weeks earlier, if possible.
If VTE develops after initiating therapy, Divigel should be discontinued.
Patients should be told to contact their doctors immediately when they are aware of a potential thromboembolic symptom (e.g. painful swelling of a leg, sudden pain in the chest, dyspepsia).
Some conditions may be aggravated during estrogen therapy or pregnancy. Women on Divigel treatment with one of the following conditions (or with a history thereof during previous pregnancy or hormone use) should therefore be closely monitored. These conditions include: Mild hypertension. Migraine or severe headache. Benign breast disease. Liver function disturbances. Cholestasis. Cholelithiasis. Diabetes mellitus. Asthma. Otosclerosis. Multiple sclerosis. Galactorrhea, elevated prolactin levels. History of herpes gestationis. Epilepsy.
Effect on ability to drive and use machines: Estrogens such as Divigel do not affect the ability to drive or use machines.