Search PubMed⌕ Search

Biomedical subjects

M H Briggs

Publications and source records attributed to M H Briggs.

At least 37 records · Page 2Linked to original sources
PubMed1980

Biochemical basis for evaluating oral contraceptives.

Oestrogens stimulate and increase HDL cholesterol concentration while progestogens decrease it; quite marked differences in effect on HDL can be demonstrated between the various oestrogen-progestogen combinations. Similar differences can be shown in their effect upon blood coagulation factors and upon the renin-angiotensin aldosterone axis. It is suggested that the selection of an oral contraceptive, in terms of cardiovascular risk, can be made from a consideration of comparative biochemical data.

Blood Coagulation Factors↗
PubMed1980

Progestogens and mammary tumours in the beagle bitch.

Progesterone administration induces specific cytosol receptors for progesterone in the mammary glands and uterus of adult beagle bitches but not in the mammary tissues or uterus of adult female rats. The specifiity of the progesterone receptor of dog myometrium is unlike that of human myometrium and is significantly different from progesterone receptors in tissues of th guinea pig. A spontaneous mammary benign mixed adenoma from an old beagle bitch was shown to contain specific progesterone receptors of similar affinity for progestogens as the dog uterine receptor. It is proposed that chronic toxicity tests of progestogens in the bitch cannot predict potential adverse human side effects because the regulatory mechanism for progesterone receptors is so different in the dog and major species differences exist in cytosol receptor affinity for particular progestational compounds.

Adenoma↗
PubMed1979

Plasma lipoprotein changes during oral contraception.

Changes in plasma concentration of high-density lipoprotein (HDL) cholesterol concentration were measured in healthy young women who received 21-days' oral treatment with either norethisterone acetate (1, 2, or 5 mg daily) or ethinyloestradiol (20 or 50 microgram daily). Similar measurements were also made in groups of women receiving progestogens or oestrogens for gynaecological indications, and in women taking oral contraceptives. Oestrogens alone stimulate increases in HDL-cholesterol, while progestogens alone suppress the concentration. Combinations of oestrogens and progestogens have variable effects depending on the relative doses and chemical compositions of the two hormones. Because HDL-cholesterol concentration is thought to be negatively correlated to cardiovascular disease risks, products which induce a large decrease are to be avoided, though other risk factors must be taken into account in the selection of oral contraceptives.

Cholesterol↗
PubMed1977

Human metabolism and steroid contraceptives. Part 1.

Metabolic activation of mestranol and certain progestagens is necessary before combination with their specific receptors. This process is subject to inhibition by other drugs. It is suggested that it is preferable to use agents not requiring metabolic activation. Widespread variation of human metabolic parameters is induced by oral contraceptives. A dose related effect of synthetic oestrogens on the synthesis and release of liver-derived plasma proteins is a major cause of this variation. The changes induced may be modified by norgestrel but not by other available progestagens. Changes in various specific plasma proteins, carrier proteins, enzymes and coagulation factors are discussed.

Blood Proteins↗
PubMed1977

Human metabolism and steroid contraceptives. Part 2.

Biochemical studies on large groups of apparently healthy women taking oral contraceptives are intended to find which organs and tissues are most stressed, in the hope than an indication of clinical side effects will result. If contraceptive steroid dose is reduced, the incidence of systemic side effects decreases and this correlates well with the decreased abnormality of many metabolic and biochemical parameters. Reduction of dosage has an equivocal effect on gynaecological side affects-some increase, some decrease. An account is given of the possible relationship between clinical side effects of oral contraceptives, and dose-related changes in plasma proteins, vitamin status and tissue enzymes.

Ascorbic Acid↗
PubMed1976

Molecular biology and oral contraception.

Recent developments in knowledge of sex hormone receptors and steroid analogue metabolism allow a rational selection of oral contraceptive steroids from among the numerous available products. Dose related metabolic effects of synthetic estrogens have been demonstrated. Many of these estrogenic actions are antagonised by norgestrel but not by any other commercially available progestogen. Generalised activation of lysosomal enzymes can be demonstrated in oral contraceptive users and is shown to be related to the total steroid dose per cycle, rather than to particular products. These findings suggest that the lowest dose combination of ethynylestradiol and d-norgestrel is the product of choice. Clinical results with such a product are described.

Blood Proteins↗
PubMed1976

Contraceptive steroid toxicology in the Beagle dog and its relevance to human carcinogenicity.

Problems associated with the use of the Beagle dog in chronic toxicological studies of contraceptive steroids are described. A short review is presented on the occurrence of spontaneous tumours in dogs and in bitches of various breeds. The current status of knowledge of canine reproductive hormones and endocrinology is outlined, together with effects of contraceptive steroids. The pathology and histological classification of spontaneous and induced mammary neoplasia in the dog is discussed and compared with breast cancer in women. A series of recommendations are included for future research in this field which it is hoped may resolve some of the outstanding issues and lead to a more suitable toxicological model for contraceptive steroids.

Animals↗
PubMed1975

Contraceptive steroid binding to the human uterine progesterone-receptor.

Using an equilibrium dialysis method, the competition was investigated between tritated-progesterone and a range of synthetic steroids for binding to 20,000 g. supernatants of human uterine endometrium and myometrium. Both types of uterine tissue showed similar patterns of progestogen binding and probably contain similar, or even identical, progesterone receptors. The gonane progestogen norgestrel binds strongly to the uterine receptors, but only the d-isomer is active. All three pregnane progestogens used in this study (chlormadinone acetate, medroxprogesterone acetate, megestrol acetate) also showed significant binding to receptors, but for the estrane progestogens, norethisterone was the only compound to show a high binding capacity. Other estranes (ethynodiol diacetate, lynestrenol, norethisterone acetate, norethynodrel) showed insignificant binding to the receptors and probably require prior metabolic activation to norethisterone before they can induce progestogenic effects.

Binding, Competitive↗
PubMed1975

Serum activity of lysosomal enzymes in relationship to contraceptive steroid dose.

Women using combined-type oral contraceptives show a progressive increase in serum activity of lysosomal enzymes (beta-glucuronidase and beta-acetyl-glucuronidase) during the first 6 cycles of treatment; thereafter, the enzyme activities remain relatively constant. The increase in enzyme activity appears to be approximately proportional to the total steroid intake per cycle and not to any particular steroid or combination of steroids. These findings suggest that oral contraceptives of choice should contain the minimum amount of steroids compatible with high efficacy and patient acceptability.

Adult↗