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Pituitary and gonadal function during the use of progesterone- or progesterone-estradiol-releasing vaginal rings.

Six women used polysiloxane vaginal rings impregnated with progesterone, or progesterone and estradiol. Nineteen 3-week treatment cycles were studied. Subjects kept records of bleeding. Plasma progesterone, estradiol, and gonadotropins were measured by radioimmunoassay. The patient acceptance was poor. None of the subjects experienced regular withdrawal bleedings during the treatment-free week. Fifty-three percent of the cycles were ovulatory as judged by plasma progesterone, but the plasma concentration of progesterone was low during the luteal phase. However, no pregnancies were discovered during the study period. Several high estradiol peaks were present during the treatment. Plasma LH fluctuated in the range of the normal menstrual cycle. Some suppression of plasma FSH was observed. The combination of estradiol and progesterone in the rings caused stronger suppression of FSH, but no diminution in the rate of ovulations or in disturbances of bleeding were observed in comparison to rings impregnated only with progesterone. Rings released the same amounts of progesterone in vitro and produced plasma concentrations which varied between 0.4 and 1.9 ng/ml.

Adult↗

Overview of the biological aspects of the fertile period.

The fertile period of the human menstrual cycle consists of those days on which sexual intercourse can result in a pregnancy. Its duration is determined by the functional life span of the gametes within the female reproductive tract. Various mechanisms control gamete transport and survival in the reproductive tract of the human female. The ovarian hormones estradiol and progesterone have an important role in regulating these mechanisms. The nature of cervical mucus and its governing influences on sperm transport and survival following coitus are of prime importance in defining the fertile days of the menstrual cycle. Man's early concepts of the fertile period were often based on erroneous theories of the female reproductive cycle. It is only since the late 1920's that a true understanding of ovulation and the menstrual cycle has evolved. Current approaches in natural family planning to recognizing the fertile and infertile days of the menstrual cycle are discussed and evaluated.

Cervix Mucus↗

Ovulation detection in the human.

The importance of predicting human ovulation for either optimizing or avoiding conception has been considered from an endocrine, morphological and clinical view point. Of the biochemical markers in peripheral blood, a knowledge of the LH peak is the most clearly defined, with a two to four fold increase above baseline levels for a relatively short 24-30 hour preovulatory period. Ovulation is considered to occur 28-36 hours after the beginning of the LH rise or 8-20 hours after the LH peak. Daily assessment of the rise in preovular oestrogen reflects Graafian follicle development but the rise is less distinct and spread over 3-4 days with marked day to day fluctuations. LH induces a marked reduction in oestrogen production some 12 hours prior to ovulation and at the same time induces a two to three fold increase in progesterone production above baseline levels. While these changes in themselves are not great enough for day to day discrimination, a knowledge of their reciprocal relationship may be. The preovular rise in FSH is relatively small compared to LH and the radioimmunoassay technique has not generally been refined to be as rapid and reliable. Monitoring the day to day growth of the preovular follicle ultrasonically is both linear and potentially predictable but there is a wide range of its final diameter (17-26 mm) prior to ovulation making prediction inaccurate. With further refinements in ultrasonic resolution, detection of intrafollicular changes of the cumulus oophorus and granulosal cell layer configuration and thickness may give a closer prediction of the time of ovulation. At a clinical level a knowledge of menstrual cycle length in association with body messages which herald ovulation are useful and may forewarn that ovulation in terms of days is approaching. Such markers as preovulation pain, the detection of periovular cervical mucus and the change in physical character and position of the cervix are reliable signs of preovulation for many well motivated and informed women for either promoting or avoiding conception. A knowledge of the basal body temperature is not a prospective guide to ovulation, but once the thermal shift is established in association with loss of periovular mucus symptoms, the fertile period can be considered to have passed. Because we do not have a precise and simple marker of human ovulation, it is necessary that the most suitable marker of pre- or postovulation is chosen for the particular need in a given individual.

Body Temperature↗

[Effect of large doses of progesterone on pregnancy, lactation and morphology of the corpora lutea].

Cells of the corpora lutea of albino rats were examined histochemically after the administration of high perogesteron doses at various periods of pregnancy and lactation. Before the prepartum exogenous progesteron failed to influence the fetal development, during the prepartum--led to prolongation of the periods of pregnancy, and by the 25th day--to the intrauterine death of the fetuses in 100% of cases. Progesteron administration during the lactation increased the lactic acid function. Saturation of the organism with exogenous progesteron was accompanied by depression of the secretory activity of the lutein cells without any functional changes in the interstitial cells. Metabolic processes were disturbed in the lutein cells, this being expressed in the interruption of formation of the secretory vacuoles, reduction of the plate complex of Golgi function and a sharp depression of the lipid synthesis. Mitochondria are subject to disintegration. A comparative morphofunctional analysis of the corpus luteum cells under conditions of directed changed hormonal balance confirmed the concept on the separate production of progestins and estrogens by two types of the secretory cells.

Alkaline Phosphatase↗

Perturbations of the human menstrual cycle by oxymetholone.

The luteolytic activity of oxymetholone, and anabolic steroid, has been evaluated in 10 women. Administration early in the follicular phase of the cycle inhibited ovulation and prolonged the duration of the cycles in 2 of 3 subjects, but treatment beginning on Day 10 (3 subjects) did not prevent ovulation, although subsequent plasma progesterone concentrations were reduced. Treatment after ovulation (4 subjects) suppressed progesterone levels by 50 to 80 per cent and shortened cycle length by 6 to 8 days. Side effects were weight gain and bromosulfophthalein retention. The most likely mechanisms producing these perturbations are the inhibition of luteinizing hormone release early in the cycle and, later, inhibition of progesterone biosynthesis.

Administration, Oral↗

Serum levels of d-norgestrel, luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone in women during and following ingestion of combination oral contraceptives containing dl-norgestrel.

Three formulations of dl-norgestrel were administered daily to groups of three women for five consecutive days. The serum levels of d-norgestrel were related to the dosage of dl-norgestrel ingested. Peak concentrations in the circulation of synthetic gestagen were attained a half hour to three hours after oral administration, followed by a rapid and sharp decline in levels until the next dose. Three women received 500 micrograms of dl-norgestrel and 50 micrograms of ethinyl estradiol for 21 days followed by six to seven days of no medication for two consecutive cycles. The gonadotropins remained suppressed for four to six days when therapy was discontinued. The daily concentrations of estradiol varied from less than 5 to 81 pg. per milliliter, and there was no difference in estrogen values during the nontreatment and treatment days. Due to the long half life of norgestrel, the one-week pill-free interval is not long enough for the complete recovery of the reproductive axis from the inhibition of oral contraceptives.

Adult↗

Studies on the mechanism of action of oral contraceptives with regard to fibrinolytic variables.

Evidence is provided that the fibrinolytic capacity in plasma is strongly dependent on circulating concentrations of tissue plasminogen activator rather than on concentrations of plasminogen activator inhibitor. Thus a decrease in plasma tissue plasminogen activator concentrations, as is the case in oral contraceptive users, may result in a decrease in plasma fibrinolytic capacity despite a parallel decrease in plasminogen activator inhibitor levels. It is now clear that the presence of specific intracellular receptors and a given motif in the genome are essential to mediate hormone-dependent regulation of gene expression. A computer search revealed potential estrogen and glucocorticoid-progesterone-responsive elements in the genes coding for tissue plasminogen activator, plasminogen activator inhibitor, and some other fibrinolytic variables. No convincing evidence for the presence of sex steroid receptors in endothelial cells was found, but liver cells clearly contain estrogen and androgen receptors. However, neither endothelial cells nor hepatocytes cultured in vitro showed a change in tissue plasminogen activator or plasminogen activator inhibitor synthesis on incubation with sex steroids (10(-9) to 10(-6) mol/L) for 3 days. An alternative explanation for the observed decreases in tissue plasminogen activator and plasminogen activator inhibitor concentrations in the plasma of oral contraceptive users is discussed.

Contraceptives, Oral, Combined↗

Hormonal consequences of missing the pill during the first two days of three consecutive artificial cycles.

The hormonal effects of the deliberate omission of a low-dose combined oral contraceptive pill (30 micrograms ethinyl estradiol + 150 micrograms levonorgestrel) during the first two days of three consecutive artificial cycles were studied in 10 women. The plasma levels of estradiol, progesterone, levonorgestrel and--whenever justified--of LH were measured three times weekly (Mondays, Wednesdays and Fridays) throughout a 90-day period, and the ovarian reaction to the prolongation of the pill-free period from 7 to 9 days was assessed. One subject (with a premature LH surge) showed a marked follicular and an inadequate luteal activity in 2 of 3 cycles. The remaining cycles were characterized by a varying degree of follicular activity associated with the absence of any luteal function. None of the subjects exhibited peripheral steroid levels indicating a normal ovulatory cycle. The results are interpreted as suggesting that repeated prolongation of the pill-free period from 7 to 9 days might result in a gradual increase in ovarian activity.

Adult↗