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At least 1,099 records · Page 61Linked to original sources
PubMed1991

The anti-progestin RU486 stabilizes the progestin-induced fatty acid synthetase mRNA but does not stimulate its transcription.

Progestins induce fatty acid synthetase (FAS) in breast cancer cell lines, both increasing its gene transcription and mRNA stabilization (Joyeux, C., Rochefort, H., and Chalbos, D. (1989) Mol. Endocrinol. 4, 681-686). In vitro run-on transcription assays show that RU486, in contrast to progestin, inhibits FAS transcription by 40-50%. Moreover and surprisingly, anti-progestin RU486 also stabilizes FAS mRNA 3- to 4-fold in MCF7 cells as measured by chase experiments in the presence of actinomycin D or cordycepin or after short cell labeling with [3H]uridine. Dexamethasone is inefficient in increasing the half-life of FAS mRNA in MCF7 cells. RU486 had no effect on MDA-MB 231 cells which contain glucocorticoid but no progesterone receptors, indicating that the progesterone receptor is implicated in this regulation. RU486-induced mRNA stabilization allows delayed accumulation of FAS mRNA. These results indicate that the progesterone receptor can be activated separately to stimulate gene transcription or stabilize mRNA.

Cell Line↗
PubMed1981

Monitoring of ovulation induction with HMG-HCG therapy by plasma estrogen and progesterone.

Seventeen patients with anovulation or luteal deficiency were tested with HMG-HCG for 40 cycles. Follicular development was monitored daily by measurement of immunoreactive plasma estrogen. Ovulation was evaluated by determination of plasma progesterone. Ovulation was induced in 16 patients and 37 of 40 cycles (93%). Fourteen pregnancies occurred in 13 patients. Plasma estrogen measurements in ovulatory cycles at the time of HCG injection ranged from 315 to 1,482 pg/ml (mean 764 pg/ml). Mild hyperstimulation occurred in two cycles with preovulatory estrogen values of 720 pg/ml and 784 pg/ml. The highest preovulatory estrogen level which was followed by anovulation was 493 pg/ml. The preovulatory estrogen peak in one triplet pregnancy measured 1,356 pg/ml. Determinants of treatment failure included inadequate follicular stimulation, interruption of HMG therapy for more than 1 day, previous ovarian wedge resection, and congenital anomaly of the uterus. Increase in body weight required higher doses of drug therapy in one case. We conclude that optimal estrogen levels prior to HCG injection range from 500 to 700 pg/ml. The risks for ovarian hyperstimulation and multiple pregnancy may be reduced and ovulation accomplished by daily administration of HMG until the defined estrogen level is reached.

Chorionic Gonadotropin↗
PubMed1976

[The low dosis gestagen therapy (author's transl)].

In young women aged 22-34 years the hormone profile under continuous therapy with 0.5 mg lynestrenol/day have been investigated. Estradiol, progesterone and FSH values have been determined in plasma by the RIA or protein-binding method, whereas LH excretion was daily measured in the urine starting on the 5th day of cycle. The low-dose-gestagen therapy shows all possible hormonal patterns ranging from the ovulatory to anovulatory one. The estradiol-17 B values in half of the patients were higher than in the cycle preceding treatment. In the first few treatment cycles all women showed markedly decreased progesterone values. However, this defect seems to recover and return to normal in later cycles. In order to be able to further explain the alterations occurring during the luteal phase under the treatment with 0.5 mg/day of lynestrenol, ovarian tissues wedge resection of women undergoing gynecological surgery has been examined macroscopically and microscopically. At the same time the hormonal profile has been determined in plasma. These investigations revealed that the morphological alterations in the ovary proceed in an unchanged way under the mentioned treatment. Histologically it could be demonstrated that ovulation is delayed by several days. The histological findings of tubal tissue (from patients who underwent sterilization) showed that the secretional activity of the tubal epithelium is considerably decreased and ciliogenesis increased. In our clinical study neither tablet nor patient failures occurred. With the exception of cycle- and tempo-disturbances no severe adverse reactions were reported. Breakthrough bleedings and spotting as well as amenorrhea in most cases manifested already in the first treatment cycles. It is important that the daily tablet is taken at midday because the maximum effect on the cervical mucus of the mini-pill therapy is most pronounced 4-6 hours after tablet intake. Especially in young patients it is recommended to get written reports on tablet intake. The strict following of these directions mainly guarantees a successful mini-pill therapy.

Adult↗
PubMed1975

Biodegradable polylactate as a steroid-releasing polymer: intrauterine administration of d-norgestrel.

Polylactate film containing 30 per cent or 4.5 mg. of d-norgestrel was fixed around a plain T-IUD and the device was inserted into the uterine cavity. Norgestrel was gradually released into the systemic circulation, blood levels being highest during menstruation. Plasma estradiol and progesterone determinations revealed that cyclic ovarian function was maintained during the intrauterine administration of norgestrel; however, marked local effects on the endometrium resulted. The amount of menstrual bleeding was reduced.

Adult↗
PubMed1991

Morphometric study of the human endometrium following continuous exposure to levonorgestrel released from vaginal rings during 90 days.

The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques. Endometrial biopsies were obtained in the luteal phase of the pretreatment cycle and on day 84-87 of the treatment period. Increased bleeding occurred in most subjects exposed to the LNG-releasing device; the mean number of bleeding and spotting days was 26.4 +/- 8.9 S.D. which exceeded that found in their control cycle. Morphometric analyses of the endometrial biopsies using 9 quantitative indices, revealed highly significant changes in glands and stroma following the use of the LNG-releasing vaginal device. Irrespective of the circulating steroid levels, the administration of LNG significantly diminished the glandular diameter (p less than 0.001), reduced the volume density of the glands (p less than 0.001) and of the glandular epithelium (p less than 0.001). and modified the ratio glandular epithelium: glands (p less than 0.001). It is concluded that levonorgestrel released at a rate of 20 micrograms/24 hrs, induces characteristic changes in the histologic structure of the human endometrium. Although no simple correlation has been found between any of the endometrial indices and the numbers of bleeding/spotting days or bleeding days, the changes as such may represent biochemical alterations which could be predisposing factors for intermenstrual bleeding and spotting. To prove a causal relationship between morphological and biochemical changes and changes in bleeding patterns, further in-depth studies may be required.

Contraceptive Agents, Female↗
PubMed1991

Effects of nomegestrol acetate (5 mg/d) on hormonal, metabolic and hemostatic parameters in premenopausal women.

The effects of nomegestrol acetate on circulating hormone levels, metabolic and hemostatic parameters and blood pressure were studied in 36 premenopausal women. The progestogen was administered from day 7 to 25 of the cycle during six cycles at a dosage (5 mg/d) known to inhibit ovulation. Analysis were performed before and in the third and sixth cycles. Estradiol and progesterone levels decreased significantly (p less than 0.001) during treatment. Body weight, fasting blood glucose and insulin, total HDL and LDL cholesterol, apolipoprotein B, fibrinogen and plasminogen did not change significantly. Triglycerides in the third cycle (p less than 0.05) and apolipoprotein A1 levels (p less than 0.01) in both periods of sampling decreased significantly. There was a significant increase in antithrombin III (p less than 0.01). These results indicate that nomegestrol acetate has no deleterious effect on blood glucose and lipids. The decrease in apolipoprotein A1 and increase in antithrombin III may be related either to the decrease in estradiol levels induced by the treatment or to the effect of the progestogen itself.

Adolescent↗
PubMed1992

Contraception with subdermal implants releasing the progestin ST-1435: a dose-finding study.

A new modified subdermal implant releasing the potent progestin ST-1435 was studied in eleven fertile-aged women. These implants have been developed for contraception and they have a life-time of two years. Three implant lengths of 4, 6 and 8 cm were tested to find the optimal steroid dose for inhibition of ovulation. Serum samples were collected twice per week during a six-week period every six months. The concentrations of serum ST-1435, estradiol and progesterone were determined by RIA. Ovulation was inhibited by all ST-1435 doses tested. The concentration of serum progesterone was below 6 nmol/l in all samples tested showing the absence of luteinization. The concentration of serum ST-1435 increased with increasing ST-1435 dose. Serum estradiol concentrations were quite variable, showing wide range and occasional high peak values typical of progestin treatment; the mean value of serum estradiol concentrations measured did not differ with different ST-1435 doses. The results of steroid determinations led to the conclusion that a single 4 cm subdermal implant is optimal for contraception. With this dosage level, ovulation is inhibited and side effects are minimized. Bleeding control was variable. No hormonal side effects due to the progestin ST-1435 were reported. This method, using a single 4 cm subcutaneous implant releasing the progestin ST-1435 with a life-time of two years, represents a promising alternative for inhibition of ovulation and contraception.

Adult↗
PubMed1987

Coagulation effects of oral contraception.

In Europe and North America, estrogen/progestogen oral contraception has been associated with an increase in venous thromboembolism, myocardial infarction, and stroke. These hazards are found mainly in smokers and in women over the age of 35. Venous thromboembolism appears to correlate with the estrogen dosage, and the arterial complications with both the estrogen and progestogen components. Blood coagulation and vascular thrombosis are intimately related. Estrogen/progestogen oral contraception affects blood clotting by increasing plasma fibrinogen and the activity of coagulation factors, especially factors VII and X; antithrombin III, the inhibitor of coagulation, is usually decreased. Platelet activity is also enhanced with acceleration of aggregation. These changes create a state of hypercoagulability that, to a large extent, appears to be counterbalanced by increased fibrinolytic activity. Studies of the oral contraceptives in current use show that the coagulation effects depend on the dosage of estrogen and the type of progestogen used in combination. Current research is aimed at finding the estrogen/progestogen formulations that induce the least changes in the coagulation system and other physiologic processes. In this respect, the new low-dose formulations are a major step forward and should reduce the risk of vascular thrombotic complications.

Blood Coagulation↗
PubMed1990

Late luteal administration of the antiprogesterone RU486 in normal women: effects on the menstrual cycle events and fertility control in a long-term study.

Twelve regularly cycling women, with contraindications to other methods of contraception, received RU486 (Roussel UCLAF, Romainville, France), once a month as a method of fertility control. The study was designed for 18 consecutive cycles. Each patient recorded basal body temperature, detected urinary luteinizing hormone peak, and collected saliva samples during each luteal phase for progesterone (P) determinations. A single dose of RU486, 600 mg, was given on the day before the expected date of the menses and 8 days later in case of continuing pregnancy after the first dose. Blood samples were collected for estradiol, P, and beta-human chorionic gonadotropin analyses on these two occasions. The compliance was poor and the results of only 137 cycles were obtained. The menstrual cyclicity was not significantly modified during this long-term study. Of the 137 cycles, 22 pregnancies occurred (16%), and 4 (18.2%) were not interrupted by the second dose of RU486. Thus, because of the high failure rate, use of RU486 at the time of the natural P withdrawal cannot be advocated as a "once-a-month" contragestive agent.

Adult↗
PubMed1992

Normative study of age variation in salivary progesterone profiles.

Daily luteal progesterone levels were measured for 124 regularly menstruating women, aged 18-44, by radioimmunoassay of steroid levels in saliva. A consistent pattern of age variation in luteal function was found, with the lowest levels of progesterone in the 18-19-year-old and 40-44-year-old groups, the highest values in the 25-34 year olds, and intermediate values in the 20-24 and 35-39-year-old groups. The striking similarity of this pattern of age variation with empirically and theoretically generated curves of apparent fecundability, suggests that age-related changes in ovarian function may underlie observed age variation in fecundability.

Adolescent↗