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Radioimmunoassay of progesterone in saliva: application to the assessment of ovarian function.

We report a specific radioimmunoassay that has the required sensitivity (7 pg per assay tube) for determining progesterone concentrations in 400 microL of mixed saliva collected from normal women. The assay is precise: intra and inter-assay variation (CV) never exceeded 11.0 and 8.0%, respectively. The assay was used to determine progesterone in saliva samples collected daily for not less than 28 days by normal women and by patients having abnormal ovarian function. Four normal women provided matched saliva and plasma samples for accurate dating of the menstrual cycle by plasma progesterone, estradiol, lutropin, and follitropin. Nine further subjects collected saliva samples only, and from these data a provisional "normal range" was established. Progesterone concentrations in saliva during the follicular phase of the cycle were low (less than 100 pmol/L) but rose beginning on day 12 to reach peak values of 230-550 pmol/L on day 21. Thereafter, progesterone concentrations in saliva declined to values generally less than 170 pmol/L at the commencement of menses. Saliva samples from three patients attending an infertility clinic were also studied to assess ovarian function.

Adult↗

[Hypophyseal reaction state during oral contraceptiva (author's transl)].

In 5 normocyclic women, firstly taking a conventional oral contraceptive, Neogynon (50 mcg EE + 250 mcg levo-norgestrel) for 6 months, the levels of LH, 17 beta-E2 and progesterone did not rise after changeover to a dose-reduced pill, Microgynon 30 (30 mcg EE + 150 mcg levo-norgestrel). This fact indicates maintained central suppression. Examination of the hypothalamic-hypophyseal axis by the Gn-RH test (50 mcg) with Microgynon 30 showed negative results during the first treatment cycle in 13 out of 18 women. In the 6th treatment cycle only 7 Gn-RH non-reactive women were observed and after stimulation with 100 mcg Gn-RH only 5 women remained with negative Gn-RH tests. Of the 20 women who took conventional oral contraceptives over a period of 6 months to 6 years (7 took Eugynon: 50 mcg EE + 500 mcg D,L-norgestrel, 5 Lyndiol: 75 mcg mestranol + 2.5 mg lynoestrenol, 8 Neogynon, only one from the Neogynon group showed a positive result. On the other hand there was a positive reaction in 4 out of 7 women using the two step dose-reduced preparation Sequilar (11 tablets of 50 mcg EE + 50 mct levo-norgestrel and 10 tablets of 50 mcg EE + 125 mcg levo-norgestrel).

Adult↗

[The importance of subsequent contraception in reducing unwanted pregnancies].

The most established hormonal method of subsequent contraception is the so-called Yuzpe-method; another important method is placement of a copper coil. Hormonal subsequent contraception has no health-hazardous side effects, so there is nothing to prevent its use but a known pregnancy. More information about subsequent contraception and easier distribution are seen as important means of decreasing unwanted pregnancies as well as abortions.

Abortion, Induced↗

The rise and fall of the British Drug Houses, Ltd.

Steroid research at BDH began in earnest in 1946-1948, when Hartley and Petrow joined the company. With the need to find new progestational agents to replace ethisterone and progesterone, the company began work. They were the first to discover the vital importance of 6-methylation in enhancing the hormonal effects of steroid hormones. Their progestational studies led them to work on antifertility agents and the development of ovulation inhibitors, the mini-pill, and preliminary studies on the postcoital pill. Their search for new steroids additionally resulted in synthesis for biological evaluation of new corticoids, anabolic agents, estrogens, and mineralocorticoids. In 1968 the company, then known as The BDH Group Ltd., was incorporated into the Glaxo Group and company research terminated.

Adrenal Cortex Hormones↗

Progesterone and estradiol receptors in the cytosol of the human uterine artery.

The binding of progesterone and estradiol to their specific cytoplasmic receptors was studied in cytosols of uterine arteries from 33 women undergoing hysterectomy. Twenty-five patients were premenopausal and one of them was pregnant. The regularly menstruating women were operated on at different phases of the menstrual cycle. Eight patients were postmenopausal with their last menstruation 4 to 30 years ago. Both progesterone and estradiol receptor concentrations were highest during the follicular phase. Decline in both receptors was observed during the early luteal phase, and this decline coincided with the luteal rise of serum progesterone. Significant correlations between steroid receptors and serum estradiol and progesterone levels were not found. The highest amounts of both receptors were found in the youngest patients. The concentrations decreased with age to undetectable levels. The decrease in progesterone receptor concentration after the menopause was statistically significant. Myometrial biopsies were taken as control material from eight women. No association could be observed between myometrial and arterial receptor concentrations.

Adult↗

Preventing ruptured ectopic pregnancy with a single serum progesterone.

Retrospective data on patients with documented ectopic pregnancies have demonstrated the potential usefulness of serum progesterone in decreasing the time to diagnosis. We report a prospective trial utilizing serum progesterone in the emergency department of a large city-county hospital. Sixty-seven ectopic pregnancies were document in the 582 patients screened; 54 (80.6%) had a progesterone level less than 15 ng/ml. Only one (1.5%) ruptured ectopic pregnancy was associated with a progesterone level greater than 25 ng/ml. There were 387 documented or presumed normal intrauterine pregnancies, 41 (10.6%) had progesterone concentrations of less than 15 ng/ml and 236 (61%) had a progesterone level greater than 25 ng/ml. We decreased minimum time of diagnosis from 48 to 72 hours to less than 24 hours by use of a progesterone screening protocol. During this time the percentage of ruptured ectopic pregnancies decreased from 79.2% to 38.8% (p less than 0.05). Because of its simple interpretation and 24-hour maximum delay, we conclude that the determination of serum progesterone should be used for ectopic pregnancy screening in all patients at risk for ectopic pregnancy, or at any time when the diagnosis is in question.

Algorithms↗

Subdermal norethindrone pellets -- a method for contraception?

The mode of action of compressed pellets containing 85 per cent norethindrone (NET) and 15 per cent cholesterol was studied. Four pellets were inserted subcutaneously, in each of five healthy volunteers and left in place for 200--229 days. The NET content of the pellets varied between 23.9 mg and 25.6 mg; and the cholesterol content between 4.2 mg and 4.5 mg. Plasma levels of NET, estradiol and progesterone were determined by radioimmunoassays. Plasma levels of NET varied mostly between 1--2 ng/ml the first month after insertion. After two months plasma levels of NET ranged between 0.5 ng/ml and 1 ng/ml in all volunteers and there was a gradual decrease of the plasma NET levels throughout treatment. Pronounced day-to-day variations in plasma NET levels were recorded. The release rates of NET was calculated to be between 187 micrograms/day and 243 micrograms/day among the five volunteers. Ovulations occurred in four out of five subjects during treatment. This study indicates that the release of gestagen from four NET pellets was only initially high enough to completely inhibit ovulation and that to accomplish full contraceptive efficacy, a higher dose, i.e. more pellets, would have to be inserted.

Adult↗

Low-level, progestogen-releasing vaginal contraceptive devices.

Silicone rubber vaginal contraceptive devices of four different formulations, which release predetermined, controlled doses of three progestogens at four distinct levels, were designed and fabricated, and tested in 90-day clinical trials. Data obtained with 70 of the devices indicated that in vivo release rates (microgram/day +/- S.D.) for the formulations were: progesterone, 1400 +/- 30; norethindrone (two levels), 49.4 +/- 2.4, 196 +/- 21; d-norgestrel, 21.6 +/- 1.4. Clinical studies with these devices indicate that the women usually ovulate (with the exception of the high-dose norethindrone-releasing devices) while sperm penetration of the cervix was inhibited by all four fromulations, most consistently by the norgestrel-releasing devices.

Contraceptive Devices↗

Long-lasting ovulation inhibition with a new injectable progestagen ORG-2154.

A new long-acting injectable progestagen was tested in 15 women who volunteered for the study. The occurrence of ovulation was assumed by the elevation of progesterone levels above 2ng/ml following a pre-ovulatory estradiol peak. Following a 200mg injection, ovulation was inhibited in all 15 women for five to ten months. In four subjects the interval between the injection and the first progesterone peak was five months. For eight, the interval was six to eight months. In the other three women, ovulation occurred more than eight months following injection. Bleeding episodes, similar to menstruation, occurred in most patients. Bleeding intervals lasting longer than 45 days occurred in nine subjects but more prolonged amenorrhea lasting longer than 60 days was reported by only five subjects. Blood chemistry which included blood cell counts, cholesterol, glucose, alkaline phosphatase, transaminases, urea nitrogen and creatinine remained within normal limits throughout the treatment.

Adult↗

Assessment of a new low-dose once-a-month injectable contraceptive.

Norethisterone (NET) in combination with mestranol (ME), in a macrocrystalline aqueous suspension that provides sustained release of steroids, was assessed as a once-a-month injectable contraceptive in ten healthy women of reproductive age. The ovarian function was studied before and after the intramuscular administration of 12mg NET plus 1.2mg ME, delivered as crystals of 150 micron average size. Serial blood samples were taken throughout the injection intervals in all women to measure serum progesterone (P), estradiol (E2), and NET. The NET/ME preparation effectively inhibited ovulation in 23 out of the 25 injection intervals studied. The administration of this formulation induced in some women a small degree of follicular maturation not followed by luteal activity. The endometrial bleeding patterns after each injection showed a bleeding-free period of two to three weeks. The overall data demonstrate that the parenteral administration of a macrocrystalline steroid preparation of NET/ME can bring about a sustained release contraceptive system at a substantially lower dose than those currently employed in once-a-month injectable contraception.

Adult↗