Medroxyprogesterone Interferes With Ovarian Steroid Protection Against Coronary Vasospasm

Miyagawa, Koichi; Rösch, Josef; Stanczyk, Frank Z.; Hermsmeyer, Kent

doi:10.1097/00006254-199709000-00020

Cited by 59 publications

(106 citation statements)

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“…Serum was obtained at 8 time points (hours 1, 2, 3, 4, 6, 8, 12, and 24) on each of days 1,8,15,22, and 29 for the purpose of measuring estradiol and progesterone. Hormone assays were done by immunoassay with the Immulite system.…”

Section: Methodsmentioning

confidence: 99%

“…7 Recent evidence has caused concern about the cardiovascular consequences of the use of medroxyprogesterone acetate and has raised the question of selecting and optimizing progestin doses and route of administration. 8,9 Various nonoral routes of administration of progesterone have been used in treating postmenopausal Time points for progesterone levels in blood serum by immunoassay are plotted individually for all 6 women at end of first week of study. Approximately 2-fold variation was seen in both peak and sustained levels, which occurred at times between 0.5 and 6 hours among women.…”

Section: Commentmentioning

confidence: 99%

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Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

Burry

Patton

Hermsmeyer

1999

American Journal of Obstetrics and Gynecology

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OBJECTIVE:The objective of this study was to evaluate the serum levels of progesterone resulting from the application of a progesterone cream to the skin. STUDY DESIGN: Six postmenopausal women were evaluated at a university clinic over a 4-week period. RESULTS: Transdermal estradiol 0.05 mg was applied 2 days before the first application of progesterone (30 mg/d) and was continued throughout the study. Patches were changed twice a week. Progesterone cream was applied once a day for 2 weeks. On day 15 and for the next 2 weeks, the progesterone cream was applied twice daily (60 mg/d). Serum 17β-estradiol and progesterone were measured at 9 different times over a 24-hour period on day 1 and at weekly intervals for the 4-week duration of the study. Serum 17β-estradiol concentrations varied among women, with mean concentrations of 40 to 64 pg/mL observed. Consistency in 17β-estradiol concentrations was found within individual persons throughout the study. Serum progesterone concentrations also varied among women, with mean concentrations ranging from 1.6 to 3.3 ng/mL. After 2 weeks of percutaneous dosing, progesterone concentrations were sustained for at least 8 hours and were consistent within a given person. An appropriate increase in progesterone concentration occurred after 4 weeks compared with 2 weeks of application. Individually, a 0.53 correlation, significant at P < .0001, was seen between the absorption of 17β-estradiol and progesterone. CONCLUSION: Significant increases in serum concentrations of progesterone were observed in all of the women studied. The percutaneous absorption of progesterone correlates strongly with the absorption of transdermal 17β-estradiol. There is variance in absorption of progesterone just as with 17β-estradiol, and the 2 measures are closely correlated. The percutaneous application of progesterone cream appears to be a safe and effective route of administration. (Am J Obstet Gynecol 1999;180:1504-11.)

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Section: Methodsmentioning

confidence: 99%

Section: Commentmentioning

confidence: 99%

Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

Burry

Patton

Hermsmeyer

1999

American Journal of Obstetrics and Gynecology

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“…Concerning the cardiovascular system, a study in rhesus monkeys has shown that estradiol plus PROG protects against coronary vasospasm, but that estradiol plus MPA failed to protect, suggesting that MPA may increase the risk of this affection (Miyagawa et al, 1997). Other studies confirm that MPA blunts the beneficial effects of estrogen and that this synthetic progestin does not exert the same effects as natural PROG.…”

Section: Hormone Replacement Therapy In Humansmentioning

confidence: 99%

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Schumacher

Weill-Engerer

Lière

et al. 2003

Progress in Neurobiology

272

171

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Without medical progress, dementing diseases such as Alzheimer's disease will become one of the main causes of disability. Preventing or delaying them has thus become a real challenge for biomedical research. Steroids offer interesting therapeutical opportunities for promoting successful aging because of their pleiotropic effects in the nervous system: they regulate main neurotransmitter systems, promote the viability of neurons, play an important role in myelination and influence cognitive processes, in particular learning and memory. Preclinical research has provided evidence that the normally aging nervous system maintains some capacity for regeneration and that age-dependent changes in the nervous system and cognitive dysfunctions can be reversed to some extent by the administration of steroids. The aging nervous system also remains sensitive to the neuroprotective effects of steroids. In contrast to the large number of studies documenting beneficial effects of steroids on the nervous system in young and aged animals, the results from hormone replacement studies in the elderly are so far not conclusive. There is also little information concerning changes of steroid levels in the aging human brain. As steroids present in nervous tissues originate from the endocrine glands (steroid hormones) and from local synthesis (neurosteroids), changes in blood levels of steroids with age do not necessarily reflect changes in their brain levels. There is indeed strong evidence that neurosteroids are also synthesized in human brain and peripheral nerves. The development of a very sensitive and precise method for the analysis of steroids by gas chromatography/mass spectrometry (GC/MS) offers new possibilities for the study of neurosteroids. The concentrations of a range of neurosteroids have recently been measured in various brain regions of aged Alzheimer's disease patients and aged non-demented controls by GC/MS, providing reference values. In Alzheimer's patients, there was a general trend toward lower levels of neurosteroids in different brain regions, and neurosteroid levels were negatively correlated with two biochemical markers of Alzheimer's disease, the phosphorylated tau protein and the ␤-amyloid peptides. The metabolism of dehydroepiandrosterone has also been analyzed for the first time in the aging brain from Alzheimer patients and non-demented controls. The conversion of dehydroepiandrosterone to 5-androstene-3␤,17␤-diol and to 7␣-OH-dehydroepiandrosterone occurred in frontal cortex, hippocampus, amygdala, cerebellum and striatum of both Alzheimer's patients and controls. The formation of these metabolites within distinct brain regions negatively correlated with the density of ␤-amyloid deposits.

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“…In addition to the possible adverse vascular effects of follicular arrest, MPA may have unwanted effects on arterial function. It has been suggested that MPA coadministration with estrogen for hormone replacement is linked to atheroma development, 6 which might be attributed to adverse effects on the endothelium. 7 In view of these data and the fact that DMPA is used for contraception in premenopausal women with cardiovascular disease, 8 we assessed the effects of long-term DMPA use on endothelial function.…”

mentioning

confidence: 99%

Long-Term Use of Contraceptive Depot Medroxyprogesterone Acetate in Young Women Impairs Arterial Endothelial Function Assessed by Cardiovascular Magnetic Resonance

et al. 2002

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Background-Depot medroxyprogesterone acetate (DMPA) inhibits proliferation of ovarian follicles, resulting in anovulation and a decrease in circulating estrogen; the latter action is potentially disadvantageous to cardiovascular health. We therefore investigated the vascular effects of long-term contraceptive DMPA in young women. Methods and Results-Endothelium-dependent (hyperemia-induced flow-mediated dilatation [FMD]) and -independent (glyceryl trinitrate [GTN]) changes in brachial artery area were measured using cardiovascular magnetic resonance in 13 amenorrheic DMPA users (Ͼ1 year use; mean age 29Ϯ4 years) and in 10 controls (mean age 30Ϯ4 years, Pϭ0.25) with regular menstrual cycles after validation of the technique. FMD and GTN responses were measured just before repeat MPA injection and 48 hours later (nϭ12) in DMPA users and during menstruation and midcycle (nϭ9) in controls. Serum-estradiol levels (S-estradiol) were measured at both visits. FMD was reduced in DMPA users compared with controls during menstruation (1.1% versus 8.0%, respectively PϽ0.01) without differences in GTN responses. S-estradiol levels in DMPA users were significantly lower than in controls during menstruation (58 versus 96 pmol/L, PϽ0.01). High levels of circulating MPA 48 hours after injection were not linked to an additional impairment in FMD (2.0% versus 3.1%, Pϭ0.23). Estradiol levels were significantly correlated to FMD (rϭ0.43, PϽ0.01). Conclusions-Endothelium-dependent arterial function measured by cardiovascular magnetic resonance is impaired in chronic users of DMPA, and hypoestrogenism may be the mechanism of action. DMPA might adversely affect cardiovascular health, and in particular its use in women with cardiovascular disease should be additionally evaluated.

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Medroxyprogesterone Interferes With Ovarian Steroid Protection Against Coronary Vasospasm

Cited by 59 publications

References 0 publications

Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

Steroid hormones and neurosteroids in normal and pathological aging of the nervous system

Long-Term Use of Contraceptive Depot Medroxyprogesterone Acetate in Young Women Impairs Arterial Endothelial Function Assessed by Cardiovascular Magnetic Resonance

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