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Some women may be unsuitable for treatment with ESTRING vaginal delivery system, in particular those with short narrow vaginas due to previous surgery, or the effects of vaginal atrophy, or those with a degree of uterovaginal prolapse severe enough to prevent retention of the ring. If you are going to have surgery, you may need to stop taking this medication. Consult your care team for advice before you schedule the surgery. For women in their 50s who are taking HRT, the figure would be 11 in 1000 , over a 5-year period (i.e. an extra 3 cases). Taking oestrogen-only HRT tablets for a long time can increase the risk of developing cancer of the womb lining (the endometrium). 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. It should be taken into account that these conditions may recur or be aggravated during treatment with ESTRING vaginal delivery system, in particular:

The following risks have been associated with systemic HRT and apply to a lesser extent for oestrogen products for vaginal application of which the systemic exposure to the oestrogen remains within the normal postmenopausal range. However, they should be considered in case of long term or repeated use of this product. Oestrogens 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 biologically active hormone concentrations are unchanged. Other plasma proteins may be increased (angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin).

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine. Get emergency help immediately if any of the following symptoms of overdose occur: Symptoms of overdose In both studies, ESTRING and conjugated estrogens vaginal cream had a similar ability to reduce vaginal pH levels and to mature the vaginal mucosa (as measured cytologically using the maturation index and/or the maturation value) after 12 weeks of treatment. In supportive studies, ESTRING was also shown to have a similar significant treatment effect on the maturation of the urethral mucosa.

Apply the gel to the right or left upper thigh on alternate days to avoid potential skin irritation. If any of the above conditions appear for the first time while taking Estring, stop taking it at once and consult your doctor immediately. The WHIMS estrogen-alone ancillary study of WHI enrolled 2,947 predominantly healthy hysterectomized postmenopausal women 65 to 69 years of age (45 percent were 65 to 69 years of age, 36 percent were 70 to 74 years of age, and 19 percent were 75 years of age and older) to evaluate the effects of daily CE (0.625 mg)-alone on the incidence of probable dementia (primary outcome) compared to placebo.

Side Effects

Tell your doctor right away if you have any serious side effects, including: nausea/vomiting that doesn't stop, mental/mood changes (such as depression, memory loss), breast lumps, unusual vaginal bleeding (such as spotting, breakthrough bleeding, prolonged/recurrent bleeding), unusual vaginal irritation/ itching/odor/discharge, severe stomach/ abdominal pain, yellowing eyes/ skin, dark urine, swelling hands/ ankles/feet, increased thirst/urination. The pharmacokinetic properties of estradiol in humans are well known and depend, in large part, on the extent to which estradiol is taken up by the systemic circulation. The clinical effects of ESTRING are therefore governed by the release characteristics of the vaginal ring delivery system.