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| Is natural progesterone the missing link in osteoporosis prevention and treatment? |
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Med Hypotheses. 1991; 35(4):316-8 (ISSN: 0306-9877)
Lee JR
Conventional treatment with vitamin D, calcium, and estrogen will delay but not reverse osteoporosis. The addition of fluoride may increase bone mass but fails to increase bone strength; fracture incidence is actually increased in non-vertebral bone by fluoride. Clearly, successful treatment of osteoporosis remains an unsolved problem. In women, osteoporosis coincides with menopause. The hypothesis that progesterone and not estrogen is the missing factor was tested in a clinical setting and was found to be extraordinarily effective in reversing osteoporosis
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| Liver metabolism during treatment with estradiol and natural progesterone. |
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Gynecol Endocrinol. 1993; 7(2):111-4 (ISSN: 0951-3590)
Darj E; Axelsson O; Carlström K; Nilsson S; von Schoultz B
Department of Obstetrics and Gynecology, Uppsala University, Sweden.
Serum concentrations of sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG), ceruloplasmin, lipoprotein A and liver enzymes were measured in 30 postmenopausal women treated with 2 mg micronized 17 beta-estradiol daily and micronized progesterone orally in doses of 50, 100 and 200 mg daily, as progestogen supplementation. The treatment lasted for 4 months. The serum levels of SHBG and CBG increased during treatment and a weak association between progesterone dosage and CBG was observed. Levels of lipoprotein A and liver enzymes did not change. It is concluded that micronized natural progesterone is an attractive means of progesterone supplementation in postmenopausal hormone replacement therapy without any liver-related side-effects.
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| Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers. |
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Neuroendocrinology. 1993; 58(4):478-84 (ISSN: 0028-3835)
Freeman EW; Purdy RH; Coutifaris C; Rickels K; Paul SM
Department of Obstetrics/Gynecology, University of Pennsylvania, Philadelphia.
Progesterone is readily reduced in humans to its A-ring metabolites, allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) and pregnanolone (3 alpha-hydroxy-5 beta-pregnan-20-one). The latter have been reported to have anxiolytic, hypnotic and anesthetic actions when administered to laboratory animals and (or) humans. Consequently, we measured allopregnanolone and pregnanolone in 18 healthy females, ages 18-25, at the time of peak plasma progesterone following an oral dose of micronized progesterone (1,200 mg) in a double-blind, placebo-controlled study. The plasma levels of the parent steroid and metabolites were compared with changes in mood, cognition, and motor performance following progesterone administration. We observed good correlations between plasma progesterone and plasma allopregnanolone (r = 0.85), plasma pregnanolone (r = 0.81) and the combined metabolites (r = 0.92). Plasma allopregnanolone was significantly correlated with measures of fatigue, confusion and immediate recall, and these correlation coefficients were somewhat greater than those for plasma progesterone and these same behavioral measures. Significant changes in fatigue, delayed verbal recall and symbol copying were experienced by subjects who achieved high levels (> or = 95.55 nmol/l) of these anxiolytic metabolites, while those with lower metabolite levels reported no negative effects. These data suggest that allopregnanolone and pregnanolone may contribute to or mediate the observed behavioral effects of progesterone.
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| Gender influences outcome of brain injury: progesterone plays a protective role. |
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Brain Res. 1993; 607(1-2):333-6 (ISSN: 0006-8993)
Roof RL; Duvdevani R; Stein DG
Brain Research Laboratory, Rutgers, State University of New Jersey, Newark 07102.
The contributions of gender and gonadal hormones in the cascade of events following brain injury are largely unexplored. We measured cerebral edema following cerebral contusion in rats under three hormonal conditions to address this issue. Normally cycling females exhibited significantly less edema than males, and pseudopregnant females were virtually spared from post-injury edema. Subsequent studies of ovariectomized females, with or without hormone treatment, indicated that the reduction of cerebral edema was associated primarily with the presence of circulating progesterone. We conclude that progesterone has a protective effect on the brain following traumatic injury. |
| Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. |
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J Am Coll Cardiol. 2000; 36(7):2154-9 (ISSN: 0735-1097)
Rosano GM; Webb CM; Chierchia S; Morgani GL; Gabraele M; Sarrel PM; de Ziegler D; Collins P
Department of Cardiology, Ospedale San Raffaele, Rome, Italy.
OBJECTIVES: We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infarction, or both.
BACKGROUND: Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women; however, women with an intact uterus also take progestin to protect against uterine malignancies. The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown.
METHODS: Eighteen postmenopausal women (mean +/- SD age 59+/-7 years) were given 17-beta-estradiol in single-blinded manner for four weeks (1 mg/day for three weeks then 2 mg/day for one week). Estradiol (2 mg/day) was then continued, and the patients were randomized (double-blind) for 12 days to either transvaginal progesterone gel (90 mg on alternate days) and oral MPA placebo (10 mg/day), or vice versa. After another two weeks on estradiol alone, the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment. Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase.
RESULTS: Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline (mean difference with 95% confidence interval [CI]: 72 s [34 to 110], p = 0.001), and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy (92 s [35 to 149], p = 0.001)). Two patients (11%) were withdrawn while taking estradiol/MPA owing to unstable angina.
CONCLUSIONS: Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia, as compared with estrogen/MPA. These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.
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| Sleep in menopause: differential effects of two forms of hormone replacement therapy. |
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Menopause. 2001; 8(1):10-6 (ISSN: 1072-3714)
Montplaisir J; Lorrain J; Denesle R; Petit D
Centre d'étude du sommeil, H pital du Sacré-Coeur de Montréal and Department of Psychiary, Université de Montréal, Québec, Canada.
OBJECTIVES: The aim of the present study was to evaluate differences between two regimens of estrogen/progestogen replacement therapy on nocturnal sleep in postmenopausal women.
METHODS: Twenty-one (21) postmenopausal women were studied. They were randomized into two treatment groups: (1) estrogen (Premarin 0.625 mg) and medroxyprogesterone acetate (Provera 5 mg) (n = 11) or (2) estrogen (Premarin 0.625 mg) and oral micronized progesterone (Prometrium 200 mg) (n = 10). Postmenopausal women were recorded for two consecutive nights in the sleep laboratory at baseline and again after 6 months of treatment in a randomized trial. The women also had to fill out evening and morning sleep and vigilance questionnaires for 7 days before baseline recordings and for 23 days before month 6 recordings.
RESULTS: Sleep efficiency was found to be significantly improved in the micronized progesterone group. It increased by 8% (p = 0.014) with no such increase observed in the medroxyprogesterone acetate group. Time spent awake after sleep onset was also significantly improved in the micronized progesterone group but not in the medroxyprogesterone acetate group. On the other hand, menopausal symptoms and subjective measures of sleep (questionnaires) improved in both groups after treatment.
CONCLUSION: This study suggests that medroxyprogesterone acetate and micronized progesterone are both effective for treating menopausal symptoms but that the latter might better improve the quality of sleep in postmenopausal women taking estrogen.
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| Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites. |
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Am J Obstet Gynecol. 1988; 159(5):1203-9 (ISSN: 0002-9378)
Arafat ES; Hargrove JT; Maxson WS; Desiderio DM; Wentz AC; Andersen RN
Science and Mathematics Division, Rust College, Holly Springs, Memphis.
Progesterone and its metabolites were measured in serum extracts by radioimmunoassay and gas chromatography-mass spectrometry, respectively, after ingestion of micronized progesterone by eight postmenopausal women. One subject received 400 mg of micronized progesterone orally that induced a hypnotic state that lasted for approximately 2 hours. Blood samples were drawn periodically from all subjects for measurement of progesterone and its metabolites in serum. Levels of serum progesterone and its metabolites increased significantly from baseline values and reached a peak between 2 and 6 hours after oral progesterone administration. Significant quantities of five compounds (progesterone, 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha,20 beta-diol, and 5 beta-pregnan-3 alpha-ol-11,20-dione) that have been reported to possess anesthetic qualities were identified. The sedative and hypnotic effects of oral administration of progesterone may be mediated through those compounds.
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| Progesterone as a bone-trophic hormone. |
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Endocr Rev. 1990; 11(2):386-98 (ISSN: 0163-769X)
Prior JC
Division of Endocrinology and Metabolism, University of British Columbia, Vancouver, Canada.
Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation. A model of the interdependent actions of progesterone and estrogen on appropriately-"ready" cells in each bone multicellular unit can be tied into the integrated secretions of these hormones within the ovulatory cycle. Figure 5 is an illustration of this concept. It shows the phases of the bone remodeling cycle in parallel with temporal changes in gonadal steroids across a stylized ovulatory cycle. Increasing estrogen production before ovulation may reverse the resorption occurring in a "sensitive" bone multicellular unit while gonadal steroid levels are low at the time of menstrual flow. The bone remodeling unit would then be ready to begin a phase of formation as progesterone levels peaked in the midluteal phase. From this perspective, the normal ovulatory cycle looks like a natural bone-activating, coherence cycle. Critical analysis of the reviewed data indicate that progesterone meets the necessary criteria to play a causal role in mineral metabolism. This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling. Much further data are needed about the interrelationships between gonadal steroids and the "life cycle" of bone. Feldman et al., however, may have been prophetic when he commented; "If this anti-glucocorticoid effect of progesterone also holds true in bone, then postmenopausal osteoporosis may be, in part, a progesterone deficiency disease."
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