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Ovarian function in amenorrheic and menstruating users of a levonorgestrel-releasing intrauterine device.

The ovarian function of 20 healthy users of a levonorgestrel-releasing intrauterine device was studied by measurements of plasma estradiol, progesterone, and levonorgestrel concentrations. Eight subjects were amenorrheic, and 12 had regular menstrual bleeding. Seventy-five percent of the subjects in both groups had ovulatory cycles. There was no difference between the mean levonorgestrel concentrations in the amenorrheic and regularly menstruating subjects. Estradiol function was undisturbed in the amenorrheic subjects with ovulatory cycles. The effect of levonorgestrel as a cause of amenorrhea is thought to be mainly of local nature. The intrauterine administration of levonorgestrel had only an occasional and weak effect on ovarian function.

Adult↗

The relationship of estrogen and progesterone to breast disease.

The rising incidence of breast cancer, coupled with awareness of the effects of hormones on breast tissue, has resulted in fears that estrogen, progesterone or both incite or adversely affect benign and malignant breast disease. An intensive review of the hormone physiology of the breast and of the numerous studies on hormones and breast disease reveals that estrogen and especially oral contraceptives not only do not cause breast cancer but may have a slight protective effect. Also, the overwhelming evidence is that the risk of benign breast disease is substantially reduced in both current and prior users of oral contraceptives.

Breast Neoplasms↗

[Studies on estradiol occupied and unoccupied receptors in human endometrial cytosol and nucleus: steroid receptors throughout the menstrual cycle and in cases of oral contraceptives administration (author's transl)].

Occupied and unoccupied estradiol (E3) receptors were investigated by exchange assay in cytosol and nuclear extract of human endometrium. Cytosol E2 and progesterone (P) unoccupied receptors and nuclear occupied E2 receptor were measured throughout the menstrual cycle and in the tissues from patients administered oral contraceptives. Sedimentation profiles of these receptors were also studied; and following results were obtained: 1) No occupied E2 receptor was observed in cytosol and almost all of those were of unoccupied type. In nuclear extract, only 0-25% of receptor was of unoccupied type and the other receptor was of occupied type. 2) Highest binding activities of cytosol E2 and P receptors were found in late proliferative phase. Maximum binding sites (Bm) were 630 and 380 f mol/mg protein and dissociation constant (Kd) was 8.9 +/- 0.7 and 4.7 +/- 0.4 x 10(-10) M, respectively. In nuclear extract, binding peaks were observed in late proliferative and late secretory phase. Bm was 1.5 f mole/microgram DNA and Kd was 12.7 +/- 1.0 x 10(-10) M.

Adult↗

The effect of the phase of the menstrual cycle and the birth control pill on athletic performance.

Investigators are not in agreement on the effects of either the phase of the menstrual cycle, or the administration of OCAs on athletic performance. It appears, however, that apart from subtle changes in some variables, for most women there is no significant effect. Medals have been won and world records set in any phase of the menstrual cycle, and also by women taking OCAs. In terms of documentation of cycle phase, newer hormonal measurement techniques such as the levels of urinary luteinizing hormone (LH) to detect ovulation or salivary progesterone, should make it easier in the future to obviate the methodologic difficulties encountered in earlier studies. Further studies should also focus on the midcycle estradiol surge as well, in order to determine the relative contributions of estrogen and progesterone to any observed performance changes. Given the possibility that some cardiovascular, respiratory, and metabolic variables may change slightly during the course of a regular ovulatory menstrual cycle, it behooves researchers who are using women as subjects in other types of studies to standardize the menstrual cycle phase in which they are tested, in order to eliminate any possible confounding effects due to hormonal variation. Regarding the effects of oral contraceptives on performance, any conclusions from the studies to date are complicated by the proliferation of preparations currently on the market. Further studies are needed on monophasic, biphasic and triphasic formulations, including OCAs with the newer progestins (desogestrel, gestodene and norgestimate), as well as the progesterone-only agents (both oral and injectable). Prospective double blind randomized studies must be done, using a proper control group. The difficulty with this technique, however, is that women in the control group will inevitably be in various phases of the cycle, so accurate hormonal documentation is also essential in order to correctly interpret the findings. Just as the past few decades have seen a significant advancement in the participation of women in sports, future years should bring an enhanced scientific knowledge base about the interactions of the special hormonal considerations of the exercising woman throughout her reproductive life cycle.

Adult↗

[Contraceptive agents and risk of thrombosis].

In the late sixties and seventies, publications of the Royal College of General Practitioners in England reported that in women using oral contraceptiva the incidence of venous thromboembolism is increased by two to four fold. Moreover, it was demonstrated, that these alterations in coagulation were induced by ethinylestradiol in a dose dependent manner. Following these findings, its dosage was lowered from more than 100 micrograms to 20-30 micrograms per day. More recently, the role of gestagens in inducing thrombosis has also been debated. Different authors observed an increased risk for venous thromboembolism in women using third generation pills containing gestoden or desogestrel compared with users of second generation levonorgestrel contraceptiva. These reports have generated a lot of concern and fear in the patients as well as doctors and have led to a drastic fall in the use of oral contraceptives. Due to the unavailability of safe contraceptive alternatives, the number of women experiencing unwanted pregnancy and its complications increased significantly. Indeed, direct proof for the role of gestagens in inducing thromboembolism is still lacking as the protocol designs of these studies do not allow us to infer whether the effects are due to the gestagens or to confounding variables. Hence, the discussions were beneficial for clinicians to remember the importance of checking the patient for individual and family risks for thrombosis before handling out a pill prescription.

Contraceptives, Oral, Hormonal↗

Sustained-release hormonal preparations XV: release of progesterone from cholesterol pellets in vivo.

Progesterone-sterol pellets were made that porvided a zero-order release of progesterone for 80 days. 4-(14)C-Progesterone was used to measure the release in vitro and in vivo. The dissolution rate in vitro (distilled water as the desorbing medium) for progesterone-cholesterol (59:41 w/w) and the progesterone-beta-sitosterol (47:53 w/w) pellets was 72 microng/100 mm2/24 hr. The average in vivo absorption from subcutaneously implanted pellets in rabbits was 2 +/- 0.1 microng/ml of plasma/cm2 of surface area. Of this amount, 20-25% was progesterone; the remainder was progesterone metabolites and conjugates. Zero-order release (plasma levels) was obtained for approximately 80 days or until about 70% of the available progesterone was exhausted. During this time, the level of excreted radioactivity in urine continuously decreased, indicating that monitoring only this parameter would lead to erroneous conclusions. A long-term effect and increased effectiveness were obtained with a 5-20-mg progesterone equivalent dose, using gel prepared from 2% methylcellulose as the suspending medium.

Animals↗

A study of the effect of mifepristone (antiprogesterone) followed by prostaglandin on uterine activity and fetal heart rate in patients having a termination of pregnancy.

In the 72 h after a single oral dose of 400 mg of the antiprogesterone mifepristone, 12 out of 14 first and one second trimester fetuses had a slight increase in heart rate; 2 fetuses died and one aborted. During the same 72 h, uterine activity increased moderately, and was physiological with no increase in resting pressure. The treatment sensitized the uterus to prostaglandin (PG) about ten-fold. A low, 0.05 mg IM, dose of sulprostone caused the demise of 5 more fetuses and caused the onset of clinical abortion in less than 2 h. After a relatively short hypertonic phase uterine resting pressure fell to normal levels and active contractions occurred leading to expulsion of uterine contents. The plasma level of progesterone (P) remained unaltered after mifepristone treatment, but the levels of estradiol 17b (E2) and cortisol increased. The plasma level of mifepristone was 1640 +/- 424 ng. ml -1 at 72 h, and the substance was still detectable after one week.

Abortifacient Agents↗