Subject(s)
Adrenocortical Hyperfunction/diagnosis , Adrenal Cortex Function Tests , Adrenal Cortex Hormones/analysis , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/diagnosis , Adrenal Hyperplasia, Congenital/diagnosis , Adrenocortical Hyperfunction/etiology , Adult , Cushing Syndrome/diagnosis , Diagnosis, Differential , Female , Humans , Hyperaldosteronism/diagnosis , Male , Middle AgedABSTRACT
PIP: MPA (medroxyprogesterone acetate), a synthetic hormone derived from progesterone, has been shown to have a strong progestational effect in both man and animals after oral administration. This is a report on a specific GLC (gas-liquid chromatographic) method for determining MPA in human plasma. Additional reagents used were: acetone, acetonitrile, benzene, cyclohexane, and heptafluorobutyric anhydride. Each of the following steps in the laboratory procedure is explained: 1) GLC; 2) mass spectrometry; 3) standard external calibration graphs; 4) plasma preparation; and 5) internal calibration graphs. After extraction of the plasma with cyclohexane and formation of the 3-enol heptafluorobutyrate ester of the drug, MPA was determined by GLC on an OV-17 column with an electron-capture detector. All results are graphed. Unfortunately, purification was impossible because MPA can be easily extracted at any pH and has a chemical structure similar to that of cholesterol.^ieng
Subject(s)
Medroxyprogesterone/blood , Chromatography, Gas/methods , Humans , Mass Spectrometry/methodsSubject(s)
Gout/drug therapy , Ketoprofen/metabolism , Phenylpropionates/metabolism , Rheumatic Diseases/drug therapy , Administration, Oral , Arthritis, Rheumatoid/drug therapy , Drug Evaluation , Humans , Injections, Intramuscular , Ketoprofen/administration & dosage , Ketoprofen/therapeutic use , Osteoarthritis/drug therapyABSTRACT
PIP: Medroxyprogesterone acetate (MAP) was administered at daily doses of 2000 mg every 12 hours for 30 days to 2 premenopausal and 8 menopausal patients suffering from advanced breast cancer. The average age was 59 years and the range was 42-70. Measurements were carried out on plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), somatotropin (GH), and prolactin (PR) by radioimmunological assay, and on 17-ketosteroids (17-KS) and 17-hydroxycorticoids (17-OCHS) in 24 hour urine samples. In 6 patients, steroid levels were measured for 2-7 months after treatment. 17-KS values dropped considerably during the 1st week of treatment but were higher than the basal values at the end of treatment, although the difference was not significant. A significant increase was observed in urinary 17-OHCS due to MAP metabolites having dihydroxyketonic side-chain. Values were also higher than basal levels in the 6 patients followed for 2-7 months. LH and FSH plasma levels dropped significantly during treatment and remained low throughout the administration periods, and values for 3 patients checked after 3-5 months were still lower than basal levels. Plasma GH, already at low basal levels, decreased further during treatment and showed no further significant changes during or after treatment. MAP at massive intramuscular doses is absorbed, metabolized, and excreted mainly by a urinary route as steroids with a dihydroxyketonic side-chain, and to a lesser extent as 17-KS. Clinically observed hypercortisonism can be explained by transformation of the steroid administered to corticord. MAP caused a strong inhibition of the pituitary, as shown by LH and FSH levels. The results of the study, while not definitive, demonstrate that the antiblastic effect of the drug can be at least partially explained.^ieng
Subject(s)
Breast Neoplasms , Hormones , Medroxyprogesterone Acetate , Neoplasms , Biology , Contraception , Contraceptive Agents , Contraceptive Agents, Female , Disease , Endocrine System , Family Planning Services , Follicle Stimulating Hormone , Luteinizing Hormone , Physiology , ProlactinSubject(s)
Benserazide/pharmacology , Bromocriptine/pharmacology , Ergolines/pharmacology , Hydrazines/pharmacology , Levodopa/pharmacology , Metergoline/pharmacology , Methysergide/pharmacology , Pituitary Gland, Anterior/metabolism , Pituitary Gland/metabolism , Prolactin/metabolism , Administration, Oral , Adolescent , Adult , Bromocriptine/administration & dosage , Clinical Trials as Topic , Drug Interactions , Female , Humans , Levodopa/administration & dosage , Male , Metergoline/administration & dosage , Methysergide/administration & dosage , Middle Aged , Pituitary Gland, Anterior/drug effects , Prolactin/blood , Secretory Rate/drug effects , Stimulation, Chemical , Time FactorsSubject(s)
Anabolic Agents/metabolism , Androstenols/metabolism , 17-Ketosteroids/urine , Chromatography, Gas , Chromatography, Paper , Chromatography, Thin Layer , Feces/analysis , Humans , Hydrolysis , Intestinal Absorption , Ketosteroids/metabolism , Steroids, Chlorinated/metabolism , Time Factors , TritiumSubject(s)
Medroxyprogesterone/metabolism , 17-Hydroxycorticosteroids/urine , 17-Ketosteroids/urine , Administration, Oral , Adult , Aged , Chromatography, Paper , Female , Humans , Injections, Intramuscular , Ketosteroids/urine , Kinetics , Male , Medroxyprogesterone/administration & dosage , Middle Aged , Oils , Pregnanes/urine , Suspensions , Tablets , TritiumSubject(s)
Adrenal Cortex Hormones/pharmacology , Adrenal Glands/drug effects , Anti-Inflammatory Agents/pharmacology , Administration, Oral , Adolescent , Adrenal Cortex Hormones/metabolism , Adult , Aged , Anti-Inflammatory Agents/metabolism , Female , Fluocinolone Acetonide/pharmacology , Humans , Injections, Intramuscular , Male , Middle Aged , Ointments , Pituitary-Adrenal Function Tests , Prednisone/pharmacology , Skin AbsorptionABSTRACT
PIP: To evaluate the effect of a progestinic-estrogenic combination on human adrenal function 2 different ratios were given, 1 pill a day for 20 consecutive days from Day 5 to Day 24 of the ovarian cycle. Medroxyprogesterone acetate, 5 mg, with ethinyl estradiol, 50 mcg, (MAP-5-EE-50) and medroxyprogesterone acetate, 2 mg, with ethinylestradiol, 75 mcg (MAP-2-EE-75) were given to 8 women. Adrenal function was determined before, during, and after therapy and urinary 17-ketosteroids (17-KA), 17-hydroxycorticosteroids (17-OHCS), pregnanediol and pregnanetriol were measured. To stimulate the adrenals iv infusion of .25 mg synthetic ACTH was administered over a period of 6 hours. Stimulation of the pituitary-adrenal axis was done by giving 4.5 gm metopirone in 6 doses in 1 day. In all subjects a definite increase of plasma corticoids was found after 20 days of therapy. In 6 of the 8 cases a definite decrease of urinary 17-OHCS was observed. Pregnanetriol excretion decreased in all cases. Pregnanediol excretion, as determined in the urine throughout the luteal phase of the ovarian cycle, was decreased by both dosages, indicating a blockage of ovulation. Urinary excretion of tetrahydrocortisol and tetrahydrocortisone was decreased in all 5 cases studied. To investigate possible change in cortisol metabolism the percentage of free and conjugated 17-OHCS was determined in 4 cases. Values were unchanged. Half-life of injected cortisol was increased and secretion rate of endogenous cortisol reduced. Added tritiated cortisol in vitro has shown a higher cortisol binding capacity of human plasma after progestinic-estrogenic therapy. Administration of ACTH in 3 cases showed an adrenal response equal to that obtained before treatment, indicating adrenal reserve had been maintained. Hypothalamic-pituitary-adrenal function, as determined with metropione, showed a decrease of urinary adrenal metabolites in all cases. Results show that the 2 doses given block ovulation and that progesterone is not produced by a corpus luteum. The progestinic-estrogenic therapy, in both doses, modified the metabolism of cortisol in the same way as estrogens alone do.^ieng