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Biomedical subjects

R Sitruk-Ware

Publications and source records attributed to R Sitruk-Ware.

At least 55 records · Page 3Linked to original sources
PubMed1987

Oral micronized progesterone. Bioavailability pharmacokinetics, pharmacological and therapeutic implications--a review.

Progesterone (P), the natural hormone, binds to its specific receptors to induce specific progestational effects. In addition to this binding, P is able to interfere with the binding sites of other steroids. Therefore the natural hormone exhibits an anti-estrogenic activity, and anti-androgenic activity and also exerts anti-mineralocorticoid effects. For a long time progesterone could not be used in clinical applications because of a rapid liver inactivation after oral administration. An oral micronized preparation of progesterone is now available which produces adequate plasma and tissue levels of progesterone. The preparation reproduces the anti-estrogenic effect of the natural hormone on the endometrium at the dose of 200 mg daily. It also reproduces the anti-mineralocorticoid effect and has no androgenic action. No side effects have been reported as far as lipids profile, coagulation factors and blood pressure are concerned. Therefore oral micronized progesterone appears suitable for hormonal replacement therapy in various areas, essentially postmenopause therapy, premenstrual syndrome, correction of irregular cycles and pregnancy maintenance.

Administration, Oral↗
PubMed1987

Prolactin secretion in benign breast diseases.

In order to evaluate the importance of prolactin in the pathogenesis of benign breast diseases (BBD), serum prolactin (PRL) levels were determined before and during a TRH challenge test in 50 patients affected by various BBD studied during the luteal phase of their cycle. They were compared to 15 normal women also studied during the luteal phase. In all the subjects estradiol (E2) and progesterone (P) were also measured. The patients were studied as a total group and in different subgroups according to the type of their disease, before and after 3 months of treatment with a potent progestin, lynestrenol. No significant differences appeared between any group of patients and the control group either on the basal prolactin secretion or on its dynamic secretory pattern after TRH injection before and during treatment. The only significant difference observed between patients and controls was the progesterone values, respectively 6.86 +/- 0.9 ng/ml and 21.2 +/- 1.4 ng/ml. It can therefore be concluded that benign breast diseases are more likely to be related to an inadequate luteal phase than to any abnormality of prolactin secretion.

Adult↗
PubMed1986

[Endocrine markers in benign breast diseases].

Estimations of estradiol, progesteron and other biochemical analyses support the hypothesis of a relative unopposed hyperestrogenism as cause of benign breast diseases. Additional factors are insufficient luteal phases combined with hyperprolactinemia or transient prolactin pulses. Progestagen treatment applied either topically or both orally and topically can correct the imbalance and perhaps prevent breast cancer.

Breast↗
PubMed1985

Breast cancer and oral contraceptives: a review.

The relationship between oral contraceptive use and breast cancer was investigated in 22 major epidemiological studies, which are reviewed in this paper. The overall risk ratio was never found to increase when computed among all users vs. nonusers. Risk increases were found in some studies within specific subgroups; but in general, if any risk exists, it is not much more than one. Future studies should focus specifically on women under age 25, on women before a first full-term pregnancy and, to a lesser extent, on perimenopausal women and on women who have had a benign breast disease.

Adolescent↗
PubMed1985

In vivo effects of progestins on prolactin secretion.

To assess a possible inhibitory effect of progestins on PRL secretion, serum PRL and estradiol levels were determined in 13 women with hyperprolactinemia due to a pituitary microadenoma before and after 3 months of treatment with a potent progestin, lynestrenol. PRL levels also were assessed during a TRH challenge test before and after treatment. Results were compared to those obtained in 10 normal women studied during the early follicular phase of their menstrual cycle and at the end of 3 months of treatment. The PRL response to TRH was blunted in patients before lynestrenol therapy. After therapy, basal serum PRL levels were significantly decreased, and the response to TRH was almost abolished. No change occurred in the normal women. The estradiol level was 80.5 +/- 7.5 (+/- SEM) pg/ml in patients before treatment and decreased to 29.2 +/- 5.0 pg/ml after therapy. Therefore, lynestrenol, a potent 19-nortestosterone derivative, exhibits in vivo an anti-PRL effect that could be related to its antiestrogenic and/or androgenic activities.

Adenoma↗
PubMed1984

[Gonadoliberin. Therapeutic prospects].

Since the luteinizing hormone-releasing hormone (LH-RH) has been identified and its mode of action understood, it has become possible to envisage a therapeutic use of long-acting, non toxic analogues. Biochemical modifications of the decapeptide have resulted in the synthesis of potent LH-RH antagonists and agonists. Paradoxically, however, the agonists, devised to induce ovulation, exert an antagonistic action due to a decrease in the number of pituitary LH-RH receptors and to desensitization of the pituitary gland to the decapeptide. These inhibitory effects are associated with the prolonged activity of the analogues, in contrast with the stimulant effects of physiological LH-RH which has a short half-life and is secreted by bursts. The direct action of LH-RH analogues on gonads suggested by animal experiments has not been found in man since human gonads are devoid of specific LH-RH receptors. Alterations in steroid production are consecutive to the rise in LH initially induced by LH-RH agonists. The complete gonadotropic inhibition which follows the administration of LH-RH antagonists or agonists suggests that these compounds could be used in man, notably for the treatment of hormone-dependent carcinomas and isosexual early puberty and in the field of contraception.

Animals↗
PubMed1983

[Progestins].

Progesterone exerts most of its actions through its specific receptors. However, synthetic progestins and progesterone itself may bind with other steroid receptors, thus producing a variety of effects. For instance, some nonsteroid derivatives produce virilizing effects by acting on testosterone receptors. In contrast, other derivatives may inhibit or potentiate the actions of androgens. Similar interactions of progestins with gluco- or mineralocorticoid receptors have been reported. The therapeutic applications of progestins are therefore extremely numerous. An improved knowledge of the mode of action of individual available progestins results in better management of a wide variety of clinical disorders including, amongst others, endometrial pathology, benign breast diseases, hirsutism and acne.

Animals↗
PubMed1980

Absorption of percutaneous oestradiol in postmenopausal women.

Seven postmenopausal women have been treated daily with 3 mg oestradiol percutaneously applied upon the skin. Blood samples were drawn at 8-h intervals during a 4-day period and on days 5, 7 and 9 from the beginning of the treatment. Plasma Plasma oestradiol (E2), oestrone (E1), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined by radioimmunoassay on these samples. The plasma E2 level was significantly increased in the 12th hour (73 +/- 17 pg/ml) but the maximal plasma concentration was obtained only at the third day of treatment (110 +/- 24 pg/ml). Thereafter the mean plasma concentration was more stable. Increments in E1 was smaller and the plasma E2/E1 ratio was 1.51. Plasma FSH and LH di not change significantly during the course of the treatment. Thus the percutaneous administration of E2 appears to be an effective and safe method of delivering E2 into the circulation, and mimicking the physiologic condition. The advantages of this method are discussed.

Estradiol↗
PubMed1979

Benign breast disease I: hormonal investigation.

One hundred eighty-four patients with benign breast disease (BBD) were studied and compared with 50 normal women. All of the women had ovulatory cycles according to a biphasic basal body temperature and a plasma prolactin in the normal range. Their corpus luteum function was evaluated by way of plasma progesterone (P) and estradiol (E2) determinations at days 5, 7, and 9 of the hyperthermic phase. In the 184 patients, plasma P over plasma E2 ratio during the luteal phase was found significantly lower than in normal women. When the patients were grouped according to type of breast lesions, it appeared that plasma P was constantly lower in all groups than in the normal women, while plasma E2 was either normal or elevated in the groups of patients with adenosis tumors and increased nodularity of both breasts. From these results it may be postulated that an imbalance in the secretion of E2 and P by the corpus luteum is a constant finding in women with benign breast disease.

Adenofibroma↗
PubMed1977

[Benign breast diseases: hormonal studies in 125 cases (author's transl)].

The results of exploration of the corpus luteum in 125 patients with benign breast disease are analysed. In 109 patients, plasma oestradiol and progesterone were measured at various times during the hyperthermic phase of the menstrual cycle. The results obtained were compared with those obtained in normal women explored during the same phase of the cycle. The average daily values for plasma progesterone obtained in this group of 109 patients was significantly lower than that found in the normal women, whilst there was no change in oestradiol levels. In addition, 16 patients were studied daily throughout the period of hyperthermia. In 8 cases, there the hyperoestrogenism, with or without progesterone insifficiency of the corpus luteum. In all, secretory imbalance of the corpus luteum with a tendency to relative or absolute hyperoestrogenism was a constant finding in women with benign breast disease.

Adult↗
PubMedDate not supplied

Progestins and cardiovascular risk markers.

Several risks are attributed to progestins as a class-effect; however, the progestins used in hormone replacement therapy (HRT) have varying pharmacologic properties and do not induce the same side effects. Natural progesterone (P) and some of its derivatives, such as the 19-norprogesterones, do not exert any androgenic effect and, hence, have no negative effect on the lipids. On the other hand, the 19-nortestosterone derivatives and even some 17-hydroxyprogesterones have a partial androgenic effect, which may explain some of the negative effects observed on surrogate markers of cardiovascular risk. The relevance of the lipid changes induced by sex steroids has been questioned, and studies in the female cynomolgous monkey have not shown a direct relationship to atherosclerosis. Results suggest that estrogens (E) have antiatherogenic effects and that P does not reverse the beneficial effect of estradiol. Also, sex hormones modulate the vasomotor response of the main arteries. E preserves the normal endothelium-mediated dilation of coronary arteries, and P does not reverse this potential cardioprotective mechanism. In the same animal model, the addition of cyclic or continuous medroxyprogesterone acetate (MPA) to E inhibited vasodilatation by 50%, while nomegestrol acetate did not diminish the E-induced vasodilatation. Not all progestins act similarly on vasomotion or affect cardiovascular risk factors in the same way. Progestins, such as MPA or norethisterone acetate (NETA), exert a partial detrimental effect on the beneficial actions of estrogens with regard to lipid changes, atheroma development, or vasomotion. In contrast, progesterone itself does not have this inhibitory effect on lipid changes and vascular reactivity in animal models or on exercise-induced myocardial ischemia in humans. Nonandrogenic molecules of P itself and of derivatives, such as 19-norprogesterones, would appear neutral on the vessels. Several ongoing randomized controlled trials of HRT are focusing on primary or secondary prevention of coronary heart disease. Unfortunately, most of these large trials have selected the same HRT regimen for their study design. Further studies with other treatment regimens are thus needed and should consider the various steroids used in different countries.

Animals↗
PubMedDate not supplied

Progestins in the menopause.

While the benefits of progestin use in hormone replacement therapy (HRT) are well recognised as far as endometrial protection is concerned, their risks and drawbacks have generated controversial articles. The data related to the progestin effect on breast tissue has been interpreted differently from country to country. However it has been admitted that, according to the type of progestin used, the dose and duration of its application, a predominant antiproliferative effect is observed in the human breast cells. As far as breast cancer risk is concerned, most epidemiological studies do not suggest any difference between the estrogens given alone or combined to progestins in HRT. When the cardiovascular risk factors are considered, some molecules with a higher androgenic potency than others, attenuate the beneficial effects of estrogens on the lipid profile and the vasomotion as well. On the other hand, other progestins devoid of androgenic properties do not exert these deleterious effects. The epidemiological data does not suggest any negative effect of the progestins administered together with estrogens on cardiovascular morbidity or mortality. However, recent results suggest that in women with established coronary heart disease (CHD), HRT may not protect against further heart attacks, when the progestin selected possesses androgenic properties. Complying with the classic contra indications of HRT and selecting molecules devoid of estrogenic, androgenic, or glucocorticoid effect should allow a larger use of the progestins without any major drawback.

Breast↗