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Biomedical subjects

D R Mishell

Publications and source records attributed to D R Mishell.

At least 109 records · Page 6Linked to original sources
PubMed1982

Correlation of ultrasonic measurement of ovarian follicle size and serum estradiol levels in ovulatory patients following clomiphene citrate for in vitro fertilization.

Ovarian follicle development was investigated in 38 normally cycling women who received clomiphene citrate, 150 mg per day for 5 days, to maximize follicular development. Ultrasonic determination of follicle growth was performed on a daily basis with a real-time sector scanner and correlated with daily concentrations of estradiol (E2) in the peripheral serum as measured by rapid radioimmunoassay. Human Chorionic gonadotropin was given to induce ovulation, and the day of injection was considered day 0. Mean concentrations of E2 reached a maximum of 1,150 +/- 65 pg/ml on day 0. Mean diameter of the dominant follicle increased to 22.1 +/- 0.4 on day 0. When peripheral concentrations of E2 were correlated with diameter and total follicular volume it was found that plasma E2 levels varied, depending on the number of follicles seen on ultrasound examination, with a mean E2 value of 459 +/- 18.9 pg/ml per follicle per day. Multiple growth of follicles occur with artificial induction of ovulation; therefore, the use of ultrasound is an important parameter to assess follicular maturation and the timing of ovulation more precisely.

Adult↗
PubMed1982

Changes in unbound sex steroids and sex hormone binding globulin--binding capacity during oral and vaginal progestogen administration.

Four groups of five cycling women each received either a contraceptive vaginal ring containing a combination of either levonorgestrel or norethindrone with estradiol or oral contraceptives containing a combination of either dl-norgestrel or norethindrone with ethinyl estradiol. Pretreatment as well as 2- and 7-week treatment serum samples were assayed for sex hormone binding globulin-binding capacity (SHBG-BC), estradiol, non-SHBG-bound estradiol, testosterone, and non-SHBG-bound testosterone, d-norgestrel, non-SHBG-bound d-norgestrel, and norethindrone. SHBG-BC was significantly increased in the norethindrone oral contraceptive group, unchanged in the norgestrel oral contraceptive group, and significantly reduced in both contraceptive vaginal ring groups. These findings indicate that the positive effect of oral ethinyl estradiol on SHBG-BC offsets the suppressive effects of d-norgestrel on SHBG-BC, while the estradiol in the d-norgestrel or norethindrone contraceptive vaginal rings is insufficient to alter the suppressive effect of d-norgestrel or norethindrone on SHBG-BC. In contrast, the ethinyl estradiol in the norethindrone oral contraceptive overcame the suppressive effect of norethindrone on SHBG-BC, resulting in a significantly increased SHBG-BC level. Although total circulating estradiol was significantly decreased in the contraceptive vaginal ring groups, the percentage of unbound serum estradiol was significantly increased in both contraceptive vaginal ring groups and significantly reduced in the norethindrone oral contraceptive group. Although total circulating testosterone was significantly reduced only in the norgestrel oral contraceptive group, the percentage and mass of unbound testosterone were significantly decreased in the norethindrone oral contraceptive group, while the percentage of unbound testosterone was significantly reduced in the norgestrel oral contraceptive group and significantly increased in the norethindrone contraceptive vaginal ring group. As levels of unbound (biologically active) steroid differ markedly from levels of total steroid, it is essential to measure levels of non-SHBG-bound estradiol and testosterone in order to determine effects of steroidal contraceptives on physiologically active circulating endogenous steroids.

Adult↗
PubMed1982

Copper intrauterine contraceptive device event rates following insertion 4 to 8 weeks post partum.

There is a consensus in the literature that intrauterine contraceptive devices (IUDs) should not be inserted within 8 weeks post partum because of reported greater rates of pregnancy, expulsion, and perforation. This greater incidence of event rates was observed in certain clinics that used large plastic IUDs, mainly the loops. In an effort to determine whether the interval from delivery to insertion of a copper-bearing IUD caused altered event rates, an analysis of studies of parous women who were using five different copper-bearing IUDs was undertaken. During the time of these studies, 411 women had an IUD inserted between 4 and 8 weeks post partum, whereas 1,197 women had the IUD inserted more than 8 weeks after a term delivery. At the end of 1 and 2 years of use, there were 4,164 and 6,816 woman months of experience, respectively, in the women with postpartum insertion, and 11,647 and 19,733 woman months of experience with insertion more than 8 weeks post partum. There were no uterine perforations in this experience, and there were no significant differences in the termination rates of any event between the two groups. This retrospective analysis indicates that copper IUDs can be inserted at the time of the routine postpartum examination without concern that the rate of accidental pregnancy, expulsion, or removal for bleeding and/or pain will be increased in comparison with a later insertion.

Female↗
PubMed1982

Noncontraceptive health benefits of oral steroidal contraceptives.

Prospective and retrospective epidemiologic studies involving oral contraceptives have been reviewed to determine the existence and extent of their benefits other than prevention of pregnancy. There is less menstrual blood loss, which reduces the risk of iron deficiency anemia by about 50%. The incidence of menorrhagia, irregular menses, and intermenstrual bleeding is also significantly reduced in users of oral contraceptives. Studies have shown an approximate 50% reduction in risk of endometrial cancer in oral contraceptive users, as well as a significant reduction in various types of benign breast disease. Because oral contraceptives inhibit ovulation, functional ovarian cysts are nearly eliminated, and the incidence of dysmenorrhea and premenstrual tension is significantly reduced. Oral contraceptives also protect women from developing ovarian carcinoma, rheumatoid arthritis, and salpingitis. From this review we conclude that the benefits of oral contraceptives in young healthy women for far outweight their more widely publicized, infrequent risks.

Adult↗
PubMed1982

The effect of gonadotropin-releasing hormone on ovarian estradiol secretion.

The present study was undertaken to determine if more than one dose of GnRh is necessary to induce luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion that is sufficient to cause a significant increase in circulating estradiol (E2) levels. Thirty-four women were studied. Of these, eight control women were studied in the early follicular phase (baseline E2, 48 +/- 4.5 pg/ml); eight patients had secondary amenorrhea caused by hypothalamic dysfunction (baseline E2, 52.0 +/- pg/ml), seven had secondary amenorrhea caused by hypothalamic pituitary failure (baseline E2, 21 +/- 2.5 pg/ml), and 11 women had amenorrhea, galactorrhea, and hyperprolactinemia (baseline E2, 16.5 +/- 3 pg/ml and baseline prolactin, 443 +/- 98 ng/ml). An initial intravenous bolus of 150 microgram of gonadotropin-releasing hormone was followed 2 hours later by a smaller dose of 50 microgram. Thirty minutes following the first and second doses of GnRH, plasma LH and FSH increased significantly in all subjects. The initial increase of LH and FSH did not result in an increase in the plasmma E2 levels in any of the subjects. However, following the second gonadotropin peak, a significant increase in plasma E2 values was observed at 4 hours in all subjects (P less than 0.01). It can be concluded that (1) GnRH can be used to induce ovarian stimulation in normal women as well as in amenorrheic patients with low or normal baseline E2 levels as long as a sequential increase in LH and FSH can be elicited and (2) hyperprolactinemia does not interfere with ovarian E2 synthesis.

Adolescent↗
PubMed1982

The effects of estrogen on adrenal androgens in oophorectomized women.

The serum levels of adrenal androgens (aa) are lower in oophorectomized (OO) than in ovulating (OV) women. This study was carried out in an effort to further investigate these findings and to study the effects of administration of estrogen on the levels of aa in OO women. Ten OO and seven OV women participated in this study in which aa were measured basally and after stimulation with adrenocorticotropic hormone (ACTH), both before and 4 weeks after conjugated estrogens (CE). Seven women received 0.625 mg of CE, and five received 2.5 mg of CE. Compared to OV women, OO women had significantly lower levels of androstenedione (Adione), dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), testosterone (T), delta 5-androstenediol (Adiol), and 17 beta-estradiol (E2) (p less than 0.01). In response to ACTH, OO women had smaller responses to Adione (p less than 0.05), DHEA (p less than 0.005), DHEA-S (p less than 0.01), 17-OH progesterone (17 Prog) (p less than 0.01), and 17-OH pregnenolone (17 Preg) (p less than 0.1). Furthermore, after ACTH, the ratio of 17 Prog/Adione was significantly higher in OO women (p less than 0.01), thus suggesting reduced 17,20-demolase (17,20D?) activity. Similarly, OO women had higher ratios of 127 Preg/17 Prog (p less than 0.1), DHEA/Adione (p less than 0.01), and Adiol/T (p less than 0.01), thereby suggesting reduced 3 beta ol dehydrogenase-isomerase (3 beta ol) activity. In response to CE, there was a dose-related increase in aa and cortisol. After 2.5 mg of CE, aa were significantly higher and similar to those levels in OV women. despite the known increases in sex hormone binding globulin-finding capacity and transcortin after estrogen, unbound T increased slightly, as did urinary free cortisol in women treated with 2.5 mg of CE. After treatment with estrogen, there was a dose-related change in the ACTH-stimulated steroid ratios that indicated and increase in 17,20D and 2 beta ol activities. In women who were gien 2.5 mg of CE, these enzyme activities were similar to those in OV women.

Adrenal Glands↗
PubMed1982

Termination of early gestation with 9-deoxo-16,16-dimethyl-9-methylene prostaglandin E2.

Vaginal suppositories containing 9-deoxo-16,16-dimethyl-9-methylene prostaglandin E2 were administered to 40 subjects in an attempt to induce an early abortion. All subjects were 49 days or less from their last menstrual period. Ten subjects (Group A) received the 75-mg suppository followed in 6 hours by a 30-mg suppository, ten subjects (Group B) received the 30-mg suppository followed in 2 hours by the 75-mg suppository and twenty subjects (Group C) received a 30-mg suppository followed in 3 hours by a second 30-mg suppository and in three more hours, at the discretion of the principal investigator, they could receive a third 30-mg suppository. Twenty-seven subjects (68%) had a successful termination of their pregnancy using the multiple vaginal prostaglandin suppository regimens. Seven subjects from Group A, 6 subjects from Group B, and 14 subjects from Group C successfully aborted. One subject in Group B and one subject in Group C were lost to follow-up and the remaining 11 subjects (28%) failed to abort. Twenty-six subjects reported side effects which included nausea, emesis, diarrhea, and uterine cramping requiring analgesia. Thirty-four subjects experienced hyperpyrexia of 99.6 degrees or greater and 12 subjects had their body temperature reach 101 degrees or higher. The use of vaginal suppositories containing 9-deoxo-16,16-dimethyl-9-methylene prostaglandin E2 did not significantly increase the overall abortifacient efficacy of this method from the 60% rate we previously observed with (15S)-15-methyl-prostaglandin F2 alpha methyl ester suppositories.

16,16-Dimethylprostaglandin E2↗
PubMed1982

A decade's experience with an individualized clomiphene treatment regimen including its effect on the postcoital test.

During a 10-year period, 428 women received clomiphene citrate according to a graduated therapeutic regimen in which the dose of clomiphene and the laboratory studies were individualized according to each patient's history, examination and response. Of the 428 patients, 85.3% ovulated and 42.8% conceived. The great majority of those who conceived did so during the first three ovulatory cycles. There was no evidence that clomiphene therapy was associated with the induction of another cause of infertility. Overall, 88.2% of those with no other causes for infertility who ovulated also conceived. However, only 7.8% of those who had one or more factors in addition to anovulation became pregnant. There was no evidence that clomiphene adversely affected the postcoital test, as only 15% of the patients had poor cervical mucus. The low rate of complications of this treatment, 5.1% cyst formation as well as the 14% abortion rate and the 2.6% congenital anomaly rate and the excellent gestational outcome in those who conceived support the use of this treatment regimen.

17-Ketosteroids↗
PubMed1982

An extended regimen of clomiphene citrate in women unresponsive to standard therapy.

An extended regimen of clomiphene consisting of 250 mg of clomiphene for 8 days followed by the administration of 10,000 IU of human chorionic gonadotropin (hCG) 6 days later was administered to 13 oligomenorrheic women who had previously failed to ovulate when treated with 250 mg of clomiphene for 5 days and hCG. Eight of these 13 women ovulated. Their postovulatory mean progesterone (P) level 7 days after hCG was 16 +/- 2 ng/ml. Three pregnancies occurred during 25 treatment cycles. Posttreatment estrogen levels were higher when women were treated for 8 days than for 5 days. Women ovulating after 8 days of treatment had increased concentrations of luteinizing hormone (LH) and testosterone (T) prior to hCG administration and higher pretreatment levels of estrogen and T, compared with women who did not ovulate. Changes in the timing of hCG administration may induce ovulation in some women who fail to ovulate when hCG is given on day 14. Because this 8-day regimen of clomiphene and hCG was successful in more than 50% of women failing to ovulate after 5 days, this regimen should be used prior to human menopausal gonadotropin (hMG) therapy.

Chorionic Gonadotropin↗
PubMed1982

The modulating role of obesity and 17 beta-estradiol (E2) on bound and unbound E2 and adrenal androgens in oophorectomized women.

17 beta-Estradiol (E2) pellet replacement therapy for oophorectomized women has been shown to be safe and effective. Some investigators have advocated the addition of testosterone (T) pellets for oophorectomized women. This study was carried out to measure the level of androgens in oophorectomized women with and without E2 pellets. The possible modulating role of E2 upon adrenal androgens was investigated as well as the effects of obesity on bound and unbound serum levels of E2 and T. Seven obese patients and eight nonobese normal patients with E2 pellets were compared to nine oophorectomized age- and weight-matched control women not receiving estrogen. Obese patients had higher levels of androstenediol (Adiol) and androstenedione (A) than nonobese patients, yet compared to oophorectomized controls, nonobese patients had higher levels of dehydroepiandrosterone sulfate (DHEA-S) and Adiol. As a group, patients with E2 pellets had higher levels of DHEA-S, Adiol A, and unbound T compared to oophorectomized controls, and their Adiol and total and unbound T levels were similar to those of premenopausal females. Obese patients had lower levels of total E2, yet a higher percentage of unbound E2, resulting in unbound E2 levels which were similar to those of the nonobese women. Unbound T was higher in obese patients compared to the nonobese women and oophorectomized controls. In conclusion, these data suggest that 1) there may be a modulating role of E2 on adrenal androgens exemplified by an increased serum level of delta 5-3 beta-ol androgens in women with E2 pellets, 2) supplemental T implants for oophorectomized women may not be necessary, and 3) obese women with pellets have higher levels of Adiol, A, and unbound T then nonobese women and therefore have a higher ratio of androgen to estrogen.

Adult↗
PubMed1982

Clinical and laboratory predictors of clomiphene response.

A prospective study was carried out on 158 anovulatory women for the purpose of finding parameters that might predict the clomiphene dose at which ovulation would occur. Both body weight and obesity were positively correlated with the dose required to achieve ovulation (P less than 0.05). Once ovulation occurred, obesity did not affect the ability to conceive. Fifty-eight women who ovulated with various doses of clomiphene, including six women who failed to ovulate, had hormonal measurements performed prior to treatment. Compared with normally ovulating controls, serum luteinizing hormone (LH), the ratio of LH to follicle-stimulating hormone (FSH), serum androgens, unbound testosterone, and unbound estradiol were elevated and sex hormone binding globulin-binding capacity (SHBG-BC) significantly lower in women receiving clomiphene. Although the ovulatory dose of clomiphene was positively correlated with both weight and obesity, neither weight nor any laboratory parameter could accurately predict the clomiphene response.

Androgens↗
PubMed1981

Functional capacity of the gonadotrophs during pregnancy and the puerperium.

The nature of secretion of gonadotropin during pregnancy and the puerperium was determined by measuring plasma levels of beta-subunit luteinizing hormone (GnRH) during the first, second, third trimesters of pregnancy, and at 10 days post partum in lactating and nonlactating women. The nonlactating subjects were divided into two groups according to whether hormonal suppression of lactation was used. Baseline and response levels of beta-LH and FSH after GnRH were below the limits of assay sensitivity (less than 0.5 ng/ml and less than 1.5 mlU/ml, respectively) in all pregnant subjects. In contrast, postpartum lactating and nonlactating subjects who received no hormonal treatment for suppression of lactation had a small but significant increase in FSH after GnRH. In lactating women, FSH increased from 1.5 +/- 0.3 mlU/ml to 2.7 +/- 0.3 mlU/ml (p less than 0.05); and in nonlactating subjects, FSH increased from undetectable levels to 2.0 +/- 0.4 mlU/ml (p less than 0.001). Patients who received estrogenic compounds for suppression of lactation had undetectable FSH baselines and no response after GnRH. beta-LH in both lactating and nonlactating women had a variable but not a significant response to one administration of GnRH. In conclusion, our findings indicate that the functional capacity of the gonadotrophs recovered earlier (at 10 days) than previously reported (less than 14 days) after term pregnancy, and the recovery of FSH secretion occurs earlier and is more consistent than the recovery of beta-LH.

Female↗
PubMed1981

Longitudinal evaluation of patients with untreated prolactin-secreting pituitary adenomas.

A group of 43 patients with galactorrhea, hyperprolactinemia, and radiographic evidence of pituitary adenomas were followed from 3 to 20 years. Initial polytomography and computerized tomographic (CT) scans revealed no evidence of extrasellar extension. Serum levels of prolactin (PRL) were measured at 6 month intervals, and visual fields were assessed annually. Polytomograms and CT scans were repeated every 9 to 36 months. During the period of follow-up, CT scans (but not polytomograms) indicated tumor enlargement in two patients, both of whom underwent selective transsphenoidal removal of the tumor. Polytomograms and CT scans did not show any change in the other 41 patients, and three of them have resumed normal menses, are no longer lactating, and have normal PRL levels. The initial results of this ongoing study indicate that most patients with small pituitary adenomas can be followed with annual CT scans with or without medical therapy, and that surgical treatment should be reserved for those patients with large tumors, those with visual-field loss, and those who show signs of enlargement of the tumor.

Adenoma↗
PubMed1981

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. II-Subjective and objective measures of effects. An international comparative trial.

Comparative clinical trials of 2 sizes of contraceptive vaginal rings and of an oral contraceptive were undertaken at 8 investigational sites (9 clinics). More than 500 women enrolled on each of the 3 study regimens. Side effects of the rings and of Nordette, the oral contraceptive, were evaluated by noting spontaneous complaints, by recording medications taken and by physical examination. Inquiries about changes in the frequency of specific conditions were made at the end of the subjects participation in the first year of the study. The incidence of spontaneous complaints was similar among users of the 2 different-sized rings and of the pill.

Adolescent↗
PubMed1981

A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. III-Menstrual patterns. An international comparative trial.

Menstrual events among users of contraceptive vaginal rings (CVRs), releasing levonorgestrel and estradiol, were studied in comparison with a combined oral contraceptive, Nordette, in multicentered trials. CVRs were made with outside diameters of 50 and 58 mm and released about 250 micrograms and 290 microgram of levonorgestrel and 150 microgram and 180 microgram of estradiol per day, respectively. The CVRs were used continuously for 3 weeks and then removed for 1 week. Both the CVRs and Nordette were perceived to reduce menstrual flow and days of menstrual bleeding. Twenty to 25% of CVR users perceived increased intermenstrual bleeding or spotting. Diaries indicate, however, that on average, CVR users experienced about 1 day per month of bleeding or spotting with the ring in place. CVRs and Nordette produced approximately the same total number of bleeding and spotting days during 6 cycles of use, 27-29, but the small (50-mm OD) ring was associated with somewhat more spotting. This ring was also associated with somewhat more prolonged bleeding and spotting runs and with more prolonged nonbleeding intervals than reported by users of the larger (58-mm OD) ring or of Nordette. Differences among regimens, however, tended to be small even when statistically significant. Evidence from menstrual diaries indicates that these CVRs, and in particular 58-mm ring, provide control over the menstrual cycle comparable to the Nordette.

Adolescent↗