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Researches of Hormone

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Advances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism.

Author : Santiago Palacios a,*, Jean-Michel Foidart b, Andrea R. Genazzani c
a. Instituto Palacios, Salud y Medicina de la Mujer, Madrid, Spain
b. Department of Obstetrics, Gynecology and Senology at the University of Liege, Belgium
c. Department of Obstetrics and Gynecology, University of Pisa, Italy

Unlike other currently available progestogens, drospirenone (DRSP) has a pharmacological profile, which closely mimics that of endogenous progesterone, most notably potent anti-aldosterone and anti-androgenic effects. Consequently, DRSP, when combined with 17ß-estradiol (E2) as hormone replacement therapy (HRT), offsets E2-related water and sodium retention by blocking the mineralocorticoid receptor. This reviewevaluates the potential benefits offered by DRSP as the progestin component of HRT with respect to its anti-aldosterone activity, which translates into positive effects on body weight and blood pressure in clinical trials of continuous, combined E2/DRSP in post-menopausalwomen. In a 1-year, large-scale, randomised, controlled trial, E2 1 mg/DRSP 2mg significantly decreased mean body weight by 1.2 kg versus baseline (P < 0.001), whereas patients receiving E2 1mg gained weight. E2 1 mg/DRSP 2mg also significantly lowered mean systolic blood pressure (SBP) by 9.0mmHg from baseline (P < 0.05) versus 3.7mmHg in the E2 1mg group (P = 0.220) in a sub-group of hypertensive women. In addition, E2/DRSP was not associated with hyperkalaemia (potassium =5.5 meq/L) irrespective of concomitant use of ACE inhibitors, angiotensin II receptor antagonists or non-steroidal anti-inflammatory drugs, and co-morbid diabetes mellitus. In summary, as well as effectively treating climacteric symptoms, DRSP 2mg combined with E2 1mg has shown positive effects on body weight and blood pressure in clinical trials, most likely due to DRSP's anti-aldosterone properties. This combination may therefore offer an alternative therapeutic option with additional benefits beyond current HRT agents for symptomatic post-menopausal women.

Published : 2006
Keywords : Progestogen; Hormone replacement therapy; Drospirenone; Post-menopausal women; Hypertension

Are genes of human intelligence related to the metabolism of thyroid and steroids hormones? – Endocrine changes may explain human evolution and higher intelligence.

Authors : H.R. Correia *, S.C. Balseiro, M.L. de Areia
Department of Anthropology, University of Coimbra, Rua Paulo Quintela, 329, Lote 7, 3A. 3030 393 Coimbra, Portugal
Abstract :

We propose the hypothesis that genes of human intelligence are related with metabolism of thyroid and steroids hormones, which have a crucial role in brain development and function. First, there is evidence to support the idea that during hominid evolution small genetic differences were related with significant endocrine changes in thyroid and steroids hormones. Second, these neuroactive hormones are also related with unique features of human evolution such as body and brain size increase, penis and breast enlargement, pelvic sexual dimorphism, active sexuality, relative lack of hair and higher longevity. Besides underling many of the differences between humans and great apes, steroids hormones promote brain growth and development, are important in the myelination process, explain sexual dimorphisms in brain and intelligence and improve specific cognitive abilities in humans. Supporting our hypothesis, recent studies indicate differences in neuroactive hormones metabolism between humans and non-human primates. Furthermore, a link between X chromosome genes and sex steroids may explain why the frequency of genes affecting intelligence is so high on the X chromosome. This association suggests that, during hominid evolution, there was a positive feedback in both sexes on the same genes responsible for secondary sexual character development and intelligence. This interaction leads to acceleration of development of human brain and intelligence. Finally, we propose that neuroactive hormone therapy may provide significant improvement in some cognitive deficits in all stages of human life and in cases of neurodegenerative diseases. However, further investigation is needed, mainly in the enzymatic machinery, in order to understand the direct role of these hormones in intelligence.

Published : 8 July 2005
Keywords : genes, hormone, hominid evolution, steroid hormones

Association between androgen receptor gene polymorphism and bone density in older women using hormone replacement therapy.

Authors: Fr´ederique Retornaz a,b, Franc¸oise Paris b, Serge Lumbrosob, Franc¸oise Audran b, Fabien Tigoulet a, C´ecile Michelon c,
Claude Jeandel a, Charles Sultan b, Hubert Blain a,*
a. Department of Internal Medicine and Geriatrics, University Hospital, Montpellier, France
b. Department of Hormonology, University Hospital, Montpellier, France
c. Department of Medical Information, University Hospital, Montpellier, France

Objective: The objective of this study was to investigate the relationship between bone mineral density (BMD) and both CAG repeat polymorphism of the androgen receptor (AR) gene and skewed X chromosome inactivation (SI) in postmenopausal women.

Methods: BMD was measured by DEXA. Both the number and the X-weighted biallelic mean of the CAG repeats of AR were analysed by PCR, before and after DNA digestion with methylation-sensitive HpaII in 192 healthy Caucasian postmenopausal women.

Results: The number of CAG repeats ranged from 10 to 34, with a median value of 22. CAG)n=22 and CAG)n=23 alleles were designated as short and long alleles, respectively. In women using hormone replacement therapy (HRT) (n = 81), lumbar spine BMD was significantly lower, and femoral neck and total body BMD marginally lower in those with long-long alleles when compared with those with other genotypes. SI (=80%) was observed in 24% of the women and was not associated with BMD. In women using HRT, femoral neck BMD was significantly lower, and lumbar spine and total body BMD marginally lower in those whose X-weighted CAG repeat biallelic was greater than 22.59 (median value) when compared to other genotypes. These results were not found in women not using HRT.

Conclusion: In conclusion, our results suggest that BMD may be associated with AR gene polymorphism in postmenopausal women using HRT but not with SI. Further studies are needed to investigate the mechanisms of the interaction between HRT, BMD and AR found in the present study.

Published: 28 April 2006
Keywords: Androgen receptor polymorphism; X-chromosome inactivation; Bone mineral density; Postmenopausal women; Osteoporosis; CAG repeat

Ethanolic extracts of black cohosh (Actaea racemosa) inhibit growth and oestradiol synthesis from oestrone sulphate in breast cancer cells

Authors : Suman Rice a, Annette Amonb, Saffron A. Whitehead a,*
a. Developmental and Endocrine Signalling, Division of Basic Medical Sciences, St. George's University of London, Cranmer Terrace, London SW17 0RE, UK
b. Bionorica AG, Neumarkt, Germany
Abstract :

Extracts of black cohosh (Actaea racemosa) and soy are used as 'natural' alternatives to conventional hormone replacement therapy (HRT) and there is some evidence that soy may protect against breast cancer by inhibiting the production of active oestrogens. This study compares the action of ethanolic extracts of black cohosh (BCE) and genistein on growth and enzyme activity in MCF-7 and MDA-MB-123 breast cancer cells. BCE inhibited growth at the two highest doses tested, i.e. 50 and 100µg/ml, whilst genistein stimulated growth in the oestrogen receptor positive (ER+) MCF-7 cells, but at high doses it inhibited growth in both cell lines. BCE did not affect the conversion of androstenedione to oestradiol and only the highest doses (50 and 100 µg/ml) significantly inhibited the conversion of oestrone to oestradiol in MDA cells. In contrast, BCE induced a dosedependent inhibition of the conversion of oestrone sulphate to oestradiol in both cell lines, whilst in human granulosa lutein (GL) cells enzyme activity was only inhibited at the highest dose of BCE. Genistein had no significant effect on enzyme activity in breast cancer cells and like BCE only the highest doses (10 and 50 µM) inhibited enzyme activity in human GL cells. In vivo genistein may have growth stimulatory effects on breast tissue but BCE not only inhibits growth but inhibits the conversion of oestrone sulphate to active oestradiol, considered by some, to be the preferred pathway of oestradiol synthesis in breast tissue.

Published: 11 October 2006
Key words: HRT, hormone, Phytoestrogens; Black cohosh; Genistein; Sulphatase; Breast cancer
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