Oestrogel Special Precautions

For the treatment of postmenopausal symptoms, HRT should only be initiated for symptoms that adversely affect quality of life. In all cases, a careful appraisal of the risks and benefits should be undertaken at least annually and HRT should only be continued as long as the benefit outweighs the risk.
Medical examination/follow-up: Before initiating or reinstituting HRT, a complete personal and family medical history should be taken. Physical (including pelvic and breast) examination should be guided by this and by the contraindications and warnings for use. During treatment, periodic check-ups are recommended of a frequency and nature adapted to the individual woman.
Women should be advised what changes in their breasts should be reported to their doctor or nurse (see Breast cancer as follows).
Investigations, including mammography, should be carried out in accordance with currently accepted screening practices, modified to the clinical needs of the individual.
Conditions which need supervision: If any of the following conditions are present, have occurred previously, and/or have been aggravated during pregnancy or previous hormone treatment, the patient should be closely supervised: Leiomyoma (uterine fibroids) or endometriosis; Risk factors for, thromboembolic disorders; Risk factors for estrogen dependent tumours, e.g. 1st degree heredity for breast cancer; Hypertension; Liver disorders (e.g. liver adenoma); Diabetes mellitus with or without vascular involvement; Cholelithiasis; Migraine or (severe) headache; Systemic lupus erythematous; A history of endometrial hyperplasia (see as follows); Epilepsy; Asthma; Otosclerosis.
Reasons for immediate withdrawal of therapy: Therapy should be discontinued if a contraindication is discovered and in the following situations: Jaundice or deterioration in liver function; Significant increase in blood pressure; New onset of severe migraine-type headache; Pregnancy.
Cardiovascular Disorders: Coronary Heart Disease and Stroke: There is no evidence from randomised controlled trials of cardiovascular benefit with continuous combined conjugated and Estrogens and medroxyprogesterone acetate (MPA). Two large clinical trials (WHI and HERS i.e. Heart and Estrogen/progestin Replacement Study) showed a possible increased risk of cardiovascular morbidity in the first year of use and no overall benefit. For other HRT products there are only limited data from randomised controlled trials to date examining effects in cardiovascular morbidity or mortality. Therefore, it is uncertain whether these findings also extend to other HRT products.
Venous Thromboembolism (VTE): Oral estrogen and estrogen/progestin therapy has been associated with an increased risk of venous thrombosis and pulmonary embolism.
The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery. As in all postoperative 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 4 to 6 weeks earlier, if possible. Treatment should not be restarted until the woman is completely mobilised.
If VTE develops after initiating therapy, the drug 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, dyspnea).
Carcinoma: Breast cancer: A randomised placebo-controlled trial, the Women's Health Initiative study (WHI), and epidemiological studies, including the Million Women Study (MWS), have reported an increased risk of breast cancer in women taking estrogens, estrogen-progestagen combinations or tibolone for HRT for several years (see Adverse Reactions).
A postmenopausal woman without a uterus who requires estrogen should receive estrogen-alone therapy, and should not be exposed unnecessarily to progestins.
HRT, especially Estrogen-progestagen combined treatment, increases the density of mammographic images which may adversely affect the radiological detection of breast cancer.
Endometrial cancer: The risk of endometrial hyperplasia and carcinoma is increased when estrogens are administered alone for prolonged periods (see Adverse Reactions). The addition of a progestagen for at least 12 days per cycle in non-hysterectomised women greatly reduces this risk. Break-through bleeding and spotting may occur during the first months of treatment. If break-through bleeding or spotting appears after some time on therapy, or continues after treatment has been discontinued, the reason should be investigated, which may include endometrial biopsy to exclude endometrial malignancy. Unopposed estrogen stimulation may lead to premalignant or malignant transformation in the residual foci of endometriosis. Therefore, the addition of progestagens to estrogen replacement therapy is should be considered in women who have undergone hysterectomy because of endometriosis if they are known to have residual endometriosis.
Ovarian cancer: Long-term (at least 5-10 years) use of Estrogen only HRT products in hysterectomised women has been associated with an increased risk of ovarian cancer in some epidemiological studies. It is uncertain whether long-term use of combined HRTs confers to a different risk than Estrogen-only products.
Other conditions: Estrogens may cause fluid retention, and therefore patients with cardiac or renal dysfunction should be carefully observed. Patients with terminal renal insufficiency should be closely observed.
Women using hormonal replacement therapy (HRT) sometimes experience increased blood pressure. Blood pressure should be monitored with HRT use. Elevation of blood pressure in previously normotensive or hypertensive patients should be investigated and HRT therapy may have to be discontinued. Clinical trials have shown that percutaneously administered 17β-estradiol (0.06%) does not affect renin substrate and has no significant effect on blood pressure in normotensive patients.
Rare cases of large increases of plasma triglycerides leading to pancreatitis have been reported with oral estrogen therapy and therefore women with pre-existing hypertriglyceridaemia should be followed closely during estrogen replacement or hormone replacement therapy.
A worsening of glucose tolerance has been observed in a significant percentage of peri- and post-menopausal patients. Therefore, diabetic patients or those with a predisposition to diabetes should be observed closely to detect any alterations in carbohydrate metabolism.
Estrogens increase thyroid binding globulin (TBG), leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 levels (by column or by radio-immunoassay) or T3 levels (by radio-immunoassay). T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Other binding proteins may be elevated in serum, i.e. corticoid binding globulin (CBG), sex hormone-binding globulin (SHBG) leading to increased circulating corticosteroids and sex steroids, respectively. Free or biological active hormone concentrations are unchanged. These patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.
Symptoms and physical findings associated with a previous diagnosis of endometriosis may reappear or become aggravated with estrogen use. For patients known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered.
Abnormal vaginal bleeding, due to its prolongation, irregularity or heaviness, occurring during therapy should prompt diagnostic measures like hysteroscopy, endometrial biopsy or curettage to rule out the possibility of uterine malignancy and the treatment should be re-evaluated.
Pre-existing uterine leiomyoma may increase in size during estrogen use. Growth, pain or tenderness of uterine leiomyoma requires discontinuation of medication.
Photosensitivity/Photoallergy: increased sensitivity to direct exposure to the sun on areas of OESTROGEL application has not been evaluated.
Effect of sunscreen application: the effects of concomitant application of OESTROGEL and a sunscreen lotion have not been evaluated.
Estradiol Transfer: the effect of estradiol transfer was evaluated in 24 healthy postmenopausal women who topically applied 1.25 g of estradiol gel once daily on the posterior surface of one arm from wrist to shoulder for a period of 14 consecutive days. On each day, one hour after gel application, a cohort of 24 non-dosed healthy postmenopausal females directly contacted the dosed cohort at the site of gel application for 15 minutes. No change in endogenous mean serum concentrations of estradiol was observed in the non-dosed cohort after direct skin-to-skin contact with subjects administered estradiol gel.
Effects on ability to drive and use machines: The effect of estrogens has not been assessed.