PubMed · 1346872
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M Whitehead, J Stevenson. 1992-02-22. Dependence and oestrogen replacement.. https://pubmed.ncbi.nlm.nih.gov/1346872/
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The pregnanolone isomers (PI) allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), isopregnanolone (3beta-hydroxy-5alpha-pregnan-20-one), epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one), progesterone, and estradiol were measured in 138 pregnant women. The sampling was carried out from the first through the 10th month of pregnancy. Gas chromatography-mass spectrometry analysis and RIA were used for the measurement of steroid levels. The ratios of individual PI were similar to those found previously around parturition: about 25:10:7:1 for allopregnanolone, pregnanolone, isopregnanolone, and epipregnanolone, respectively. All the PI showed a significant increase during pregnancy, which was more pronounced in the 3alpha-steroids. The results indicated changing ratios between 3alpha- and 3beta-PI and between 5alpha- and 5beta-PI throughout pregnancy. The constant allopregnanolone/isopregnanolone ratio found through pregnancy weakened the hypothesis of the role of isopregnanolone in the onset of parturition. The ratio of estradiol (stimulating uterine activity) to 5alpha-PI and epipregnanolone exhibited significant changes during pregnancy in favor of estradiol up to the sixth or seventh month, in contrast to the constant estradiol/pregnanolone ratio. A pregnancy-stabilizing role of pregnanolone, counterbalancing the stimulating effect of estradiol on the onset of parturition, was suggested.
Estradiol derivatives bearing HS-, HSCH(2)-, HSCH(2)CH(2)-, MeS-, MeSCH(2)-, MeSCH(2)CH(2)-, or PhCH(2)SCH(2)CH(2)-groups at the 11beta position or an HS-group at the 7alpha position have been synthesized, and their binding affinity to the estrogen receptor (ER) determined. Nearly all of these substituted estrogens retain high binding affinity, and at the 11beta position, the sulfur atom has an effect on ER binding that is similar to that of a carbon atom. These thiol derivatives are promising intermediates for the preparation of a variety of estradiol conjugates. The methyl sulfides, in particular, might potentially be developed as (11)C-labeled agents for imaging ER-positive tumors by positron emission tomography.
OBJECTIVE: To assess if regular physical exercise or oral oestradiol therapy decreased vasomotor symptoms and increased quality of life in previously sedentary postmenopausal women. SETTING: A prospective, randomised trial at a University Hospital. METHODS: 75 postmenopausal, sedentary women with vasomotor symptoms were randomised to: exercise three-times weekly over 12 weeks (15 women), oral oestradiol therapy for 12 weeks (15 women) and 45 women to three other treatment arms. Results from the exercise and oestradiol groups are presented here. The effects on vasomotor symptoms and wellbeing were assessed with logbooks and validated questionnaires. RESULTS: Ten women fulfilled 12 weeks of exercise. The number of flushes was rather unchanged in five women and decreased to 28% (range 18-42%) of baseline in the other five women. Five of the ten women continued to exercise another 24 weeks, thus in all 36 weeks. The mean number of flushes decreased by about 50% in these five women (from 6.2/24 to 3.2 flushes/24 h at 36 weeks). In the same group a score made as the product of reduction in number and severity of flushes decreased by 92% at 12 weeks, 75% at 24 weeks and 72% at 36 weeks compared with baseline. In the estrogen group flushes decreased from 8.4 to 0.8 (P<0.001) after 12 weeks of therapy and remained at this level after 36 weeks. Well-being according to different measurements improved significantly in both groups, albeit more markedly in the estrogen group. CONCLUSIONS: Apart from many other health benefits regular physical exercise may decrease vasomotor symptoms and increase quality of life in postmenopausal women, but this has to be further evaluated scientifically. Exercise should be introduced gradually to ensure compliance.