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Biomedical subjects

I Schiff

Publications and source records attributed to I Schiff.

At least 91 records · Page 5Linked to original sources

The effects of progestins on vasomotor flushes.

For patients with severe vasomotor flushes who require therapy but for whom estrogens are contraindicated, progestins can be tried. These drugs appear to offer the benefit of a reduction of vasomotor flushes without such unwanted side effects as the increased risk of contracting endometrial cancer. However, progestins cannot replace estrogens universally since there is no evidence that they prove effective against osteoporosis-related fractures and genital atrophy. Nonetheless, as more physicians begin to add medroxyprogesterone acetate to the estrogen regimen to reduce the risk of endometrial hyperplasia, it might be that a lower dose of estrogen will be necessary to relieve flushes. We hope that this additive effect exists, although it has not yet been shown. Whether or not the addition of medroxyprogesterone will carry risks or counteract the beneficial effects of estrogens on such disorders as osteoporosis remains to be elucidated. What is clear from the medroxyprogesterone and estrogen studies is that whenever these drugs are discontinued, the vasomotor flushes can recur, albeit with less intensity and less frequency.

Administration, Oral↗

Objective evidence that placebo and oral medroxyprogesterone acetate therapy diminish menopausal vasomotor flushes.

The vasomotor flush (VMF) is the most common reason for menopausal women to seek hormonal therapy, but the evaluation of therapeutic regimens has been hampered by the observation that placebo therapy can decrease VMF and, until recently, by a lack of objective criteria of measurement of the VMF. Using the objective criteria of temperature elevations (TEs) and luteinizing hormone (LH) pulses, we evaluated the effect of placebo and medroxyprogesterone acetate (MPA) on VMF. MPA and possibly also placebo were found to reduce not only the subjectively noted VMF but also the frequency of TEs recorded. In addition, MPA, but not placebo, significantly reduced the frequency and amplitude of LH pulses. Possible mechanisms of action of MPA and placebo therapy are discussed.

Body Temperature↗

Ovarian failure in long-term survivors of childhood malignancy.

The frequency and causes of ovarian failure among 182 long-term survivors of childhood cancer were examined. Twenty-two patients (12%) had ovarian failure. Ovarian failure was found in 17 of 25 patients (68%) who had both ovaries within abdominal radiotherapy fields, in five of 35 patients (14%) whose ovaries were at the edge of the treatment field, and in none of 122 patients with one or both ovaries outside of an abdominal treatment field (p < 10(-4)). The odds for ovarian failure in patients with both ovaries in the field are 19.7 higher than those for other irradiated patients (95% confidence interval, 5.3 to 72.8). Covariate and multivariate analyses of tumor type, age at diagnosis, duration of follow-up, abdominal tumor surgery, abdominal radiotherapy, number of chemotherapeutic agents administered, and cumulative doses of several drugs revealed that the location of the ovaries relative to radiation treatment fields was the only risk factor for subsequent ovarian failure.

Abdominal Neoplasms↗

Relationship among estrogen-induced psychophysiological changes in hypogonadal women.

Estrogen treatment of 16 hypogonadal women showed lessening of gonadotrophins, vasomotor symptoms, psychometrically measured aggression, and average sleep latency, but more Rapid Eye Movement sleep in a 100-day cross-over, double-blind comparison with placebo treatment. Of eight insomniac subjects, four showed decreased, but four showed increased insomnia scores and sleep latencies. Clinical rank of psychological intactness correlated with sleep latency and with total sleep time during the estrogen condition. Although estrogen altered both physiological and psychological states, such effects were characterized by different time courses and different degrees of consistency among the subjects.

Affect↗

Plasma estriol and its conjugates following oral and vaginal administration of estriol to postmenopausal women: correlations with gonadotropin levels.

A study was designed to compared the metabolic fate and the biologic effects of 4 mg of estriol (E3) administered either orally or vaginally to six postmenopausal women. Blood samples were collected every hour for 6 hours and five different estriol fractions as well as gonadotropins were measured. Vaginal E3 administration resulted in a decline of 45% in luteinizing hormone (LH) levels and 17% in follicle-stimulating hormone (FSH) levels at 6 hours after treatment (p < 0.05). In contrast, the administration of 4 mg of E3 orally did not produce a decline of LH and FSH, despite the fact that the serum levels of E3-3-sulfate, E3-3-sulfate-16-glucosiduronate, estriol-3-glucosiduronate, and estriol-16-glucosiduronate were all fourfold to 24-fold higher after oral administration than after vaginal estriol administration. However, since the levels of unconjugated E3 were higher after the vaginal than after the oral administration of estriol, we conclude that only unconjugated E3 suppresses gonadotropins.

Administration, Oral↗

Oral medroxyprogesterone in the treatment of postmenopausal symptoms.

A double-blind crossover study was designed to compare the effects of placebo and medroxyprogesterone acetate, 20 mg, on vasomotor flushes and blood hormones in 27 postmenopausal women. In women receiving placebo, vasomotor flushes were decreased by 25.9% during the last four weeks of treatment compared with baseline, and a further decrease of 34.5% was achieved by the last four weeks after patients were given medroxyprogesterone. In women who initially took medroxyprogesterone, there a 73.9% decline by the last four weeks in the number of vasomotor flushes. However, when these women were given placebo, an immediate worsening of their symptoms occurred. The drug produced a decline of 27% and 29% in serum levels of follicle-stimulating hormone and luteinizing hormone, respectively, while the serum prolactin level rose slightly. Thus, medroxyprogesterone can be used to treat the vasomotor flushes of postmenopausal women when estrogen use is undesirable.

Administration, Oral↗

Interactions of oestrogens and hours of sleep on cortisol, FSH, LH, and prolactin in hypogonadal women.

The effects of conjugated oestrogens 0.625 mg and placebo on adrenal and pituitary hormones were compared in 10 postmenopausal women during their sleep by means of double blind prospective crossover study. On placebo, the women had nocturnal variations in LH, prolactin and cortisol concentrations. However, oestrogen administration selectively blunted LH and prolactin changes, but not the rise in cortisol.

Adult↗

Abnormal adrenal responses to adrenocorticotropic hormone in hyperandrogenic women.

The plasma concentrations of testosterone (T), dehydroepiandrosterone (D), androstenedione (A), pregnenolone (delta 5P), progesterone (P), 17-hydroxypregnenolone (17-delta 5P), 17-hydroxyprogesterone (17-P), 11-deoxycortisol (S), and cortisol (F) were measured before, and 30 and 60 minutes after, a bolus intravenous injection of 25 units of adrenocorticotropic hormone (ACTH) in nine normal women and in fifteen patients with a variety of manifestations of androgen excess. Patients with androgen excess demonstrated significantly higher mean baseline levels of T, D, A, delta 5P, 17-delta 5P, and 17-P. After a bolus intravenous injection of 25 units of ACTH, higher-than-normal increments were noted for the following steroids: delta 5P (one patient), 17-delta 5P (one patient), D (two patients), P (one patients), 17-P (two patients), and S (two patients). Following ACTH injections, the ratios of increments in plasma steroid pairs were computed to estimate the efficiency of several adrenal enzymes, and evidence suggesting partial deficiency of 3 beta-hydroxysteroid dehydrogenase delta 4-5 isomerase (five patients) and 11 beta-hydroxylase (five patients) was found. In addition, 6 of the 15 patients with androgen excess exhibited an abnormally high increment in D relative to the increment in F. The data show that apparent abnormalities in adrenal steroid biosynthesis are a frequent occurrence in patients with hyperandrogenism.

17-alpha-Hydroxypregnenolone↗

Characterization of hyperandrogenism with insulin-resistant diabetes type A.

The characterization of the hyperandrogenism of two sisters with type A insulin-resistant diabetes and hirsutism is presented. Testosterone (T) and androstenedione levels were elevated in peripheral serum. These were not markedly affected by infusion of adrenocorticotropic hormone. In patient 1 glucocorticoid suppression decreased T levels by 50% and androstenedione levels by 30% but had no effect on them in patient 2. Estrogen-progestin suppression markedly reduced testosterone levels in both patients. The blood production of T in patient 1 was 0.8 mg/day and in patient 2 was 4.5 mg/day, both of which are elevated. Selective venous catheterization in patient 2 revealed markedly elevated testosterone levels in the ovarian veins, and polycystic ovaries were found at subsequent laparotomy. These endocrine studies have shown that the source of excessive testosterone in these patients is excessive production by the ovaries, and it can be suppressed by oral contraceptives.

Adolescent↗

The effect of varicocelectomy on sperm count, motility, and conception rate.

One hundred and eighty-seven male partners of involuntarily infertile couples were evaluated and found to have dilatation of the left spermatic vein. One hundred and forty-nine underwent varicocelectomy and achieved a statistically significantly improved conception rate as compared with the nonoperated group. Although 70.5% of men whose wives subsequently conceived had improved semen count and motility postoperatively, no parameter distinguished these men from other patients with similar improvement who remained infertile.

Female↗

The use of constant infusion of unlabeled dehydroepiandrosterone for the assessment of its metabolic clearance rate, its half-life, and its conversion into estrogens.

We have exploited the feasibility of utilizing constant infusion of unlabeled dehydroepiandrosterone (DHEA) for calculating its MCR, its half-life (t1/2), and its conversion ratio into estrogens. In nonpregnant women, results obtained by infusion of unlabeled DHEA were similar to those obtained by the infusion of either labeled steroid or a mixture of labeled and unlabeled steroid. An increase of 3-fold in the infusion rate did not change any of these results, indicating that enzyme availability was not a limiting step in the production of estradiol (E2) from DHEA. When compared to the nonpregnancy state, term pregnancy was not associated with a change in plasma DHEA concentrations, but the MCR of DHEA of 76.8 +/- 18.8 (SE) liters/kg.day was 2.5-fold higher and the t1/2 of 22.5 +/- 3.6 min was 2-fold lower. The conversion ratio of DHEA into E2 increased during pregnancy by 500-fold, and DHEA contributed 9% of maternal circulating E2. In the first postpartum day, the MCR of DHEA and its t1/2 were not significantly different from those of term pregnancy, suggesting that the increased MCR of DHEA in pregnancy was not solely due to increased clearance of DHEA by the placenta.

Adult↗

Suppression of prolactin and gonadotropin secretion in post-menopausal women by 2-hydroxyestrone.

An infusion of 2-hydroxyestrone given to estrogen primed post-menopausal women resulted in a rapid and total suppression of serum prolactin. Serum LH responded with an initial rise followed by a 30% decrease below baseline values. Serum FSH exhibited a significant suppression below preinfusion levels. The catechol estrogen had no effect on serum LH, FSH and PRL in post-menopausal women who were not pretreated with estrogens. This impact of 2-hydroxyestrone on pituitary hormone secretion provides for the physiological role of this non-uterotropic estrogen in the neuroendocrine mechanisms of the human.

Estrone↗

The intraovarian sites of androgen and estrogen formation in women with normal and hyperandrogenic ovaries as judged by in vitro experiments.

The status of oocytes, the follicular fluid concentrations of steroids, and the in vitro steroidogenic capacities of stromal tissue, thecal tissue, and granulosa cells from a 15-yr-old girl with primary amenorrhea, ovarian hyperandrogenism, insulin-resistant diabetes mellitus, and acanthosis nigricans were compared to those from normal adult human ovaries. Most oocytes (95%) in the antral follicles recovered from the hyperandrogenic ovaries were degenerative, and the antral fluid levels of testosterone were 30- to 200-fold higher than those in normal ovaries. Granulosa cells from the hyperandrogenic ovaries produced mainly estradiol as did those from normal healthy follicles. The thecal tissues produced 2- to 6-fold more androgen than similar tissues from normal ovaries. However, the stroma from the hyperandrogenic ovaries produced 49- to 250-fold more testosterone than that generated by normal tissues. These data suggest that the removal of stromal tissue as well as follicular tissue from patients with certain types of hyperandrogenism may sometimes contribute to a reduction in androgen secretion.

Adolescent↗