Disease relevance of Farlutal

• Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm [1].
• After adjusting for possible underascertainment of cancer because of incomplete follow-up, we found the relative risk for medroxyprogesterone users to be 0.7 for breast cancer (95% confidence limits, 0.3 to 1.4), 1.2 (95% confidence limits, 0.1 to 6.7) for cancer of the uterine corpus, and 0.8 (95% confidence limits, 0.1 to 4.6) for ovarian cancer [2].
• Risk of breast, uterine corpus, and ovarian cancer in women receiving medroxyprogesterone injections [2].
• Nine adult patients with obstructive sleep apnea syndrome were administered medroxyprogesterone acetate, 60 to 120 mg/day, and the effect of medroxyprogesterone on clinical symptoms and obstructive apneas during sleep was assessed [3].
• CONCLUSIONS: During an average follow-up of 4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone acetate did not reduce the overall rate of CHD events in postmenopausal women with established coronary disease [4].

Psychiatry related information on Farlutal

• Before medroxyprogesterone therapy, responders were distinguished from nonresponders only by the presence of a significantly lower resting arterial oxygen tension during wakefulness [3].
• Conjugated equine estrogen plus medroxyprogesterone acetate also increased the overall risk of myocardial infarction and stroke in women without coronary heart disease, and myocardial infarction or death in women with coronary heart disease, and also increased the risk of breast cancer, cognitive decline and dementia [5].
• Medroxyprogesterone acetate as a treatment for sexual acting out in organic brain syndrome [6].
• Continuous positive airway pressure and administration of medroxyprogesterone acetate prevented further episodes and relieved much of the somnolence and lethargy that had contributed to the evidence for myxedema [7].
• Forty-eight male patients with long-standing histories of deviant sexual behavior received medroxyprogesterone acetate and milieu therapy for up to 12 months [8].

High impact information on Farlutal

• Coronary vasospasm in response to pathophysiological stimulation without injury showed that progesterone plus estradiol protected but medroxyprogesterone plus estradiol failed to protect, allowing vasospasm [1].
• SETTING: Inpatient Clinical Research Center. PARTICIPANTS: Twelve healthy postmenopausal women receiving oral estrogen (estradiol, 1 mg/day) and progestin (medroxyprogesterone acetate) replacement therapy were compared with 12 postmenopausal women who were not using estrogen replacement therapy (ERT) [9].
• We characterize a subgroup of patients who benefit from medroxyprogesterone therapy by reducing obstructive apneas during sleep [3].
• Inhibitory effect of medroxyprogesterone acetate on foreign body tumorigenesis in mice [10].
• Effect of medroxyprogesterone and an aorta-derived cell growth inhibitor on B16 melanoma in mice [11].

Chemical compound and disease context of Farlutal

• We conclude that medroxyprogesterone in contrast to progesterone increases the risk of coronary vasospasm [1].
• Tamoxifen versus medroxyprogesterone acetate for metastatic breast cancer [12].
• Phase II study of aminoglutethimide and medroxyprogesterone acetate in the treatment of patients with advanced breast cancer [13].
• This randomized placebo-controlled trial (Heart and Estrogen/Progestin Replacement Study) of conjugated equine estrogens plus medroxyprogesterone failed to show the anticipated reduction in CHD, and at the same time the threefold increase in venous thromboembolism confirmed that HRT is procoagulant [14].
• METHODS: A total of 135 postmenopausal women (aged 41-70 years) with no evidence of moderate or severe periodontal disease were randomized to receive daily oral conjugated estrogen (Premarin; 0.625 mg) alone or in combination with medroxyprogesterone acetate (Prempro; 0.625 and 2.5 mg, respectively) or placebo [15].

Biological context of Farlutal

• Hematocrit fell from 56 +/- 2.5% to 50 +/- 1.2%, a mean fall of 6% (P less than 0.01), during medroxyprogesterone acetate therapy [16].
• Pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate in advanced breast cancer patients [17].
• Effect of medroxyprogesterone acetate on proliferation and cell cycle kinetics of human mammary carcinoma cells [18].
• Risk was also elevated among those reporting a prior ovarian cyst, medroxyprogesterone use, a first degree family history of cancer, and occupational exposure to paint [19].
• CONCLUSIONS: Cyclic medroxyprogesterone increased spinal bone density in physically active women experiencing amenorrhea or ovulatory disturbances [20].

Anatomical context of Farlutal

• An aorta-derived inhibitor of endothelial cell and tumor cell growth and medroxyprogesterone, which depresses collagenase expression in vivo, were tested alone and in combination against B16-F10 melanoma in C57BL/6 mice in such doses that either agent alone had little effect [11].
• (1) progestin (medroxyprogesterone acetate, MPA) alters neointima formation in injured carotid arteries, (2) addition of MPA alters the antiproliferative effects of estrogen, and (3) an interaction between MPA and estrogen can be accounted for by MPA-induced alterations in serum 17 beta-estradiol levels [21].
• As we have shown before, the progestin, medroxyprogesterone acetate, increased the level of both EGF mRNA and TGF alpha mRNA in this cell line [22].
• In a series of 19 experiments, formation of sub- and supranuclear vacuoles, which reflects accumulation of glycogen in response to medroxyprogesterone acetate added to the medium, was observed in well-preserved glandular epithelial cells only when the level of cytosolic progesterone receptor was above 300 fmol/mg protein [23].
• From 1984 to 1989 5 mg of medroxyprogesterone was added from day 14 to 25 of every sixth month in subjects with an intact uterus [24].

Associations of Farlutal with other chemical compounds

• The treated group received intramuscular injections of 100 microgram of estradiol valerate daily from day 1 to day 12 and 15 mg of medroxyprogesterone acetate from day 7 to day 12 [25].
• Daily subcutaneous injections of medroxyprogesterone acetate (8 mg/kg) plus testosterone (1 mg/kg) (MT group) were administered for 55 days (experiment A) or 15 days (experiment B) [26].
• Those who had not had hysterectomies (n = 16,049) were randomly assigned to receive estrogen plus progestin (n = 8,240), given as 0.625 mg/day conjugated equine estrogens plus 2.5 mg/day medroxyprogesterone acetate, or placebo (n = 7,809), with a mean followup of 5.6 years [27].
• Furthermore, progesterone receptor levels measured in this way were comparable to those obtained using progesterone, R5020, or medroxyprogesterone acetate as labeled ligands [28].
• METHODS: Seventy-six postmenopausal women, age 51.6 +/- 3.9 yr with body mass index of 24.9 +/- 3.2 kg/m2, were randomized to conjugated estrogens (0.625 mg) plus medroxyprogesterone acetate (2.5 mg) or placebo daily [29].

Gene context of Farlutal

• Medroxyprogesterone acetate therapy in advanced breast cancer: the predictive value of androgen receptor expression [30].
• Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate [31].
• Progestins with androgen receptor agonist activity, such as medroxyprogesterone acetate, also suppress estrogen's effects on LDLR expression through their androgenic properties [32].
• CONCLUSION: Medroxyprogesterone acetate 60 mg daily for 2 weeks has both immediate (FSH, LH, and SHBG), prolonged (LH), and rebound endocrinologic (prolactin) effects up to 6 weeks after treatment [33].
• CONCLUSION(S): The administration of oral, but not transdermal, E2 plus medroxyprogesterone acetate at the usual clinical doses used in postmenopausal women decreased IGF-1 levels and the response of GH to GHRH in older women [34].

Analytical, diagnostic and therapeutic context of Farlutal

• A double-blind crossover study was designed to compare the effects of placebo and medroxyprogesterone acetate, 20 mg, on vasomotor flushes and blood hormones in 27 postmenopausal women [35].
• Mouse mammary tumors induced by medroxyprogesterone acetate: immunohistochemistry and hormonal receptors [36].
• Injectable contraception (medroxyprogesterone acetate) in rural Bangladesh [37].
• In the 2 patients who had cardiac catheterization before and during medroxyprogesterone acetate therapy, mean pulmonary arterial pressure fell 13 and 19 mm Hg [16].
• Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study [38].

References