Double-blind, placebo-controlled psychometric studies of a combined estrogen-progestin regimen versus estrogen alone on performance, mood and personality of menopausal syndrome patients
Department of Psychitry, University of Vienna, Vienna, Austria. Arzneimittel-Forschung
(Impact Factor: 0.7).
02/2001; 51(3):238-45. DOI: 10.1055/s-0031-1300030
The influence of a combined estrogen-progestin regimen (Climodien) on noopsyche, thymopsyche, personality and psychophysiological measures of menopausal syndrome patients was investigated in a double-blind, placebo-controlled, comparative, randomized 3-arm trial phase (Climodien 2/3 = estradiol valerate (CAS 979-32-8) 2 mg + the progestin dienogest (CAS 65928-58-7) 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P) followed by an open-label phase in which all patients received Climodien 2/2 (estradiol valerate 2 mg + dienogest 2 mg) = regimen A*. 49 women (16, 17, 16 valid patients per arm) aged between 46 and 67 years (mean 58, 58, 56 years, respectively) with the diagnoses of insomnia (G 47.0) related to postmenopausal syndrome (N 95.1) were included in the analysis of the double-blind phase. Both the double-blind and the open-label phase lasted 2 months. Noopsychic investigations demonstrated an improvement in associative verbal memory after 2 months of regimen A, which was significant as compared with both baseline and placebo. Regarding visual memory, regimen A* induced an improvement, which was significantly different from the decline in correct reproductions in the Benton Test observed under estradiol. Errors in the Benton Test decreased significantly after regimen A* as compared with regimen EV. These findings suggest that hormone replacement therapy with estradiol, and even more in combination with dienogest, improves verbal and visual memory, which is in line with the improvement in information processing speed and capacity objectified by event-related potentials (ERP). Thymopsychic investigations demonstrated a significant improvement in somatic complaints and trait anxiety after both regimen A and regimen EV as compared with baseline. State anxiety decreased significantly under regimen A* as compared with EV. The Freiburger Personality Inventory showed an improvement in aggressivity after regimen A* as compared with the preceding placebo as well as an improvement in striving after dominancy after both regimen A and regimen EV as compared with pre-treatment, but also after regimen A* as compared with regimen EV. Extraversion increased after 2 months of regimen A as compared to regimen P. Psychophysiological findings including pupillary and skin conductance variables were not significant.
Available from: Pierrick Poisbeau
- "Les e ´ tudes montrant un effet bé né fique des estrogè nes ont porté sur la mé moire verbale a ` court et a ` long terme. Les six e ´ tudes cliniques randomisé es mené es chez des femmes a ˆ gé es de moins de 65 ans, montrent une amé lioration de la mé moire verbale par rapport au placebo (Hackman et Galbraith, 1976 ; Krug et al., 2003 ; Linzmayer et al., 2001 ; Maki, 2006 ; Phillips et Sherwin, 1992 ; Shaywitz et al., 2003 ; Sherwin, 1988). Au contraire, deux e ´ tudes randomisé es chez des patientes a ˆ gé es de plus de 65 ans ne retrouvent aucun effet (Binder et al., 2001 ; Grady et al., 2002). "
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ABSTRACT: Epidemiological studies of Alzheimer disease have shown a higher prevalence of women. Some data argue for a link between Alzheimer disease and the decrease of estrogen in post-menopausal women. Animal studies have shown a beneficial effect of estrogen on memory with a decrease of amyloid deposition in models of AD, whereas estrogen has a positive effect on BDNF. Six studies have shown a positive effect of estrogen therapy on memory and studies on structural and functional imaging have shown a beneficial effect of estrogens but the largest study on prevention of dementia with estrogens (WHI) showed a deleterious effect. To better understand this paradoxical situation, we reviewed the literature on estrogens, memory and Alzheimer disease. We first discuss the promnesic effect of estrogen on mice and rats, second the neuroprotector effect of estrogen on animal models of Alzheimer disease, and third the available human studies. We hypothesize a link with the time of instauration of the estrogen treatment. Nevertheless this hypothesis remains to be demonstrated.
Available from: Johann-Matthias Graf von der Schulenburg
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ABSTRACT: Estradiol valerate 2mg/dienogest 2mg is an oral estrogen/progestogen formulation that has been approved throughout the European Union for the treatment of climacteric symptoms in postmenopausal women.
▴ Dienogest is a progestogen that combines the properties of both progesterone and 19-nortestosterone derivatives. It has moderate affinity for the progesterone receptor, significant antiproliferative and antiandrogenic activity, and produces secretory transformation of the endometrium.
▴ Estradiol valerate is an esterified form of natural 17β-estradiol, the most potent endogenous human ovarian estrogen, and is hydrolysed to estradiol soon after oral administration.
▴ Results from a randomised, double-blind, multicentre trial showed that oral estradiol valerate 2mg/dienogest 2mg and estradiol valerate 2mg/dienogest 3mg once daily for 1 year were each as effective as estradiol 2mg/estriol lmg/norethisterone acetate lmg in the treatment of climacteric symptoms in 581 postmenopausal women; reductions from baseline in Kupperman Index scores were 78.5, 74.5 and 75.0%, respectively.
▴ The number of days without any type of bleeding was lowest in patients treated with estradiol valerate 2mg/dienogest 2mg (8.7 days), and highest in the estradiol valerate 2mg/dienogest 3mg group (12.1 days). During the twelfth month of treatment with estradiol valerate 2mg/dienogest 2mg, the percentage of patients who reported bleeding was 14.5%.
▴ Endometrial biopsy results were similar in patients treated with estradiol valerate 2mg/dienogest 2mg, estradiol valerate 2mg/dienogest 3mg or estradiol 2mg/estriol lmg/norethisterone acetate lmg once daily for 1 year; 90.8, 87.4 and 87.5% of samples, respectively, contained atrophic material. Proliferative material was found in 4.2, 2.5 and 4.4% of the biopsies, respectively; there was no incidence of hyperplasia in any of the treatment groups.
▴ A noncomparative muticentre study in 1501 postmenopausal women demonstrated that adverse events associated with estradiol valerate 2mg/dienogest 2mg once daily for 48 weeks included breakthrough bleeding, mastalgia, headache, abdominal pain, hypertension, thrush, migraine, weight gain, increase in endometrial thickness and metrorrhagia.
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