Source: Health Products Regulatory Authority (IE) Revision Year: 2020 Publisher: Novo Nordisk A/S, Novo Alle, DK-2880, Bagsvaerd, Denmark
Pharmacotherapeutic group: Natural and semisynthetic estrogens, plain
ATC code: G03CA03
The active ingredient, synthetic 17β-estradiol, is chemically and biologically identical to endogenous human estradiol. It substitutes for the loss of oestrogen production in menopausal women, and alleviates menopausal symptoms. Relief of menopausal symptoms is achieved during the first few weeks of treatment.
Oestrogens prevent bone loss following menopause or ovariectomy.
Oestrogen deficiency at menopause is associated with an increasing bone turnover and decline in bone mass. The effect of oestrogens on the bone mineral density is dose-dependent. Protection appears to be effective for as long as treatment is continued. After discontinuation of HRT, bone mass is lost at a rate similar to that in untreated women.
Evidence from the WHI trial and meta-analysed trials shows that current use of HRT, alone or in combination with a progestagen – given to predominantly healthy women – reduces the risk of hip, vertebral, and other osteoporotic fractures. HRT may also prevent fractures in women with low bone density and/or established osteoporosis, but the evidence for that is limited.
The effects of Estrofem on bone mineral density were examined in a 2-year randomised, double-blind, placebo-controlled trial in early postmenopausal women (n=166, including 41 on Estrofem 1 mg and 42 on Estrofem 2 mg). Estrofem 1 mg and 2 mg significantly prevented bone loss at the lumbar spine and total hip in comparison with the placebo-treated women. The overall difference in mean percentage change in bone mineral density versus placebo was for 1 mg and 2 mg respectively 4.3% and 5.3% at the lumbar spine, 4.0% and 3.9% at the femoral neck. The corresponding numbers for the trochanter were 3.3% and 3.2% after 2 years of treatment.
The percentage of women who maintained or gained BMD in lumbar zone during treatment was 61% and 68% in women treated with 1 mg and 2 mg Estrofem respectively.
Following oral administration of 17β-estradiol in micronised form, rapid absorption from the gastrointestinal tract occurs. It undergoes extensive first-pass metabolism in the liver and other enteric organs, and reaches a peak plasma concentration of approximately 44 pg/ml (range 30-53 pg/ml) within 6 hours after intake of 2 mg. The half-life of 17β-estradiol is about 18 hours. It circulates bound to SHBG (37%) and to albumin (61%), while only approximately 1-2% is unbound. Metabolism of 17β-estradiol occurs mainly in the liver and the gut but also in target organs, and involves the formation of less active or inactive metabolites, including estrone, catecholoestrogens and several oestrogen sulfates and glucuronides. Oestrogens are excreted by the bile, where they are hydrolysed and reabsorbed (enterohepatic circulation), and mainly in urine in biologically inactive form.
The toxicity profile of estradiol is well-known. There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SmPC.
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