Spotlight on Estradiol-Intranasal in the Management of Menopause
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Estradiol-intranasal is a nasal spray formulation containing an aqueous solution of 17β-estradiol that has a unique pulse-like pharmacokinetic profile. In a well designed, placebo-controlled trial estradiol-intranasal 200 to 400 µg/day significantly reduced the incidence and severity of climacteric symptoms in women with moderate to severe menopausal symptoms after 4 and 12 weeks’ treatment. The efficacy of estradiol-intranasal 300 µg/day was similar to that of oral estradiol 2 mg/day in this and another double-blind placebo-controlled trial. This equivalent efficacy was maintained in a subgroup of women with initially severe symptoms, and in smokers.
Reductions in the incidence of atrophic vaginal mucosa and genitourinary symptoms and increases in the karyopyknotic index achieved with estradiol-intranasal 300 µg/day were also similar to those observed with oral estradiol 2 mg/day. Assessments of the effects of estradiol-intranasal on the complications of menopause (increased risk of cardiovascular disease and osteoporosis) are ongoing; however, estradiol-intranasal (sequentially combined with a progestogen) produced significant beneficial effects on some lipid parameters and on markers of bone resorption and formation, and bone mineral density in postmenopausal women. Estradiol-intranasal had no significant effects on serum levels of most of the assessed hemostatic factors, or on angiotensinogen or insulin levels.
Estradiol-intranasal 100 to 600 µg/day was generally well tolerated in clinical trials and most adverse events were mild to moderate. The most commonly reported events were nasal symptoms and mastalgia. There was no evidence of endometrial hyperplasia with up to 1 year’s treatment with estradiol-intranasal 300 µg/day combined with a progestogen. The incidence of mastalgia and withdrawal or breakthrough bleeding was lower with estradiol-intranasal 300 µg/day than with oral estradiol 2 mg/day (both administered with a progestogen) in one trial. In another trial, the incidence of mastalgia was lower with estradiol-intranasal 300 µg/day than with estradiol transdermal 50µg (both administered with a progestogen). However, the overall incidence of adverse events was similar between the two treatments in this trial.
In conclusion, estradiol-intranasal 200 to 400 µg/day (optimal initiating dose 300 µg/day) reduces the incidence and severity of menopausal climacteric symptoms and has a good tolerability profile. Thus, evidence to date suggests that estradiol-intranasal is a useful treatment option for menopausal symptoms.
KeywordsEstradiol Estrone Follicle Stimulate Hormone Level Dydrogesterone Climacteric Symptom
The full text article in Drugs 2001; 61 (15): 2243-2262 was reviewed by: A.R. Gambacciani, Department of Obstetrics and Gynaecology, University of Pisa, Pisa, Italy; D. Herrington, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA; F.W.H.M. Merkus, Leiden-Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands; G. Samsioe, Department of Obstetrics and Gynaecology, Lund University, Lund, Sweden; F.Z. Stanczyk, Women & Children’s Hospital, Los Angeles, California, USA; J. Studd, Chelsea and Westminister Hospital, London, England; W. Utian, University Macdonald Women’s Hospital, Cleveland, Ohio, USA
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