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Biomedical subjects

H L Judd

Publications and source records attributed to H L Judd.

At least 127 records · Page 7Linked to original sources
PubMed1982

Biologic effects of various doses of ethinyl estradiol in postmenopausal women.

To determine which dosage of estrogen might provide physiologic replacement while minimizing adverse effects, 20 postmenopausal women were studied before and after oral administration of ethinyl estradiol. Twenty premenopausal women studied in the early and late follicular phases of the menstrual cycle were presumed to reflect normal physiologic function. Variable responses of the different biochemical and biologic markers to the actions of ethinyl estradiol were observed. Liver protein synthesis was the most sensitive measure of the action of ethinyl estradiol. In comparing the relative potencies of ethinyl estradiol with previously reported results observed with the usage of conjugated equine estrogens, the actions of 10 micrograms ethinyl estradiol were approximately equivalent to the biologic effects of 1.25 mg conjugated estrogens. The results suggest that ethinyl estradiol is far more potent than previously believed and that the daily administration of 10 micrograms, a dose lower than currently available commercial preparations, may be adequate for relief of symptoms of vaginal atrophy and may provide protection from the occurrence of osteoporotic fractures.

Administration, Oral↗
PubMed1982

Estrogen levels in postmenopausal women with hot flashes.

Following menopause, some women are troubled by hot flashes (episodes of flushing and perspiration), whereas others do not experience the symptom. To determine whether the extent of estrogen deficiency influences the occurrence of the disturbance, the authors measured the levels of estradiol (E2), estrone (E1), and sex-hormone binding globulin (SHBG), and the percent and total non-SHBG-bound E2 in 24 women with frequent hot flashes and 24 women who had never experienced the symptom. Significantly lower levels of E2 (P less than .002), E1 (P less than .05), percent non-SHBG E2 (P less than .05), and total non-SHBG-bound E2 (P less than .01) were found in the symptomatic women. Similar differences were confirmed in 18 subject pairs matched for age, years since menopause, and presence or absence of ovaries. The finding of a significantly (P less than .05) lower percent ideal body weight in the women with hot flashes suggests that the known effects of body weight on the rate of extraglandular estrogen production and the level of SHBG in postmenopausal women may be important variables determining the occurrence of hot flashes.

Age Factors↗
PubMed1982

Origin of serum estradiol in postmenopausal women.

In postmenopausal women, the circulating levels of estrone (E1) and estradiol (E2) may be of clinical importance. The origin of E1, but not of E2, has been defined. To examine the source of the latter, the serum concentrations, metabolic clearance rates, conversion ratios, and production rates of testosterone (T), androstenedione (A), E2, and E1 were measured in 20 postmenopausal subjects. For E2, the mean +/- SE CRTE2 was 0.0014 +/- 0.0005; thus, the contribution of circulating T to the circulating E2 pool was minimal (2.5%). The contribution of circulating A to E2 was also insignificant, whereas the CRE1E2 was appreciable (0.065 +/- 0.011), accounting for 21.5% of the E2 pool. For E1, the major contribution was the peripheral conversion of A, accounting for 24.6% of circulating E1. The contribution of peripheral conversion of T (unmeasurable) and E2 (2.9%) to the E1 pool were minimal. These data are consistent with the concept that in postmenopausal women the major contribution of peripheral conversion to the circulating E2 pool is from E1, which in turn is the product of peripheral aromatization of circulating A.

Androstenedione↗
PubMed1982

In vivo effects of delta 1-testololactone on peripheral aromatization.

To evaluate the in vivo effect of delta 1-testololactone on peripheral aromatization, studies were performed on seven postmenopausal women with metastatic breast cancer. Analysis of variance indicated that there were significant increases of circulating androstenedione (p less than 0.05) and estradiol (p less than 0.001) during administration of different doses of testololactone. Androstenedione levels were increased with all doses of testololactone tested (50, 100, 250, and 500 mg every 6 hr for 14 days each), while estradiol rose with only the 250- and 500-mg dosages. With administration, there was a significant decrease of estrone (p less than 0.001) with the mean level falling from 26 +/- 3 (S.E.) to 11 +/- 2 pg/ml. The addition of adrenal suppression (dexamethasone, 1 mg nightly at 11 p.m.) significantly lowered androstenedione (p less than 0.05) but had no effect on estrone or estradiol levels. Long-term therapy (up to 6 months) with the 250-mg dosage showed continual suppression of estrone with no escape being observed. Studies to determine the reason for the increase of estradiol with testololactone suggested cross-reactivity of the antibody with in vivo metabolites of the drug. However, these possible metabolites did not bind to uterine cytosol estrogen receptors. The decrease in estrone with testololactone administration presumably explains its antitumor properties.

Aged↗
PubMed1982

Effect of clonidine on hot flashes in postmenopausal women.

The effectiveness of clonidine in suppressing the occurrence of postmenopausal hot flashes was examined using a dose-response study design and objective recordings of hot flashes. Patients with frequent flashes were studied before and after oral administration of placebo and 0.1, 0.2, and 0.4 mg of clonidine daily for 2 weeks at each dose level. Finger temperature and skin resistance were recorded as indices of hot flash episodes. Four of 10 subjects beginning the study withdrew because of drug-related side effects. Clonidine was found to reduce significantly the frequency of hot flashes as compared with baseline (P less than .005) and with effects of the placebo (P less than .05). At the maximum dosage the mean rate of hot flash occurrence decreased 46%. It was concluded that clonidine does reduce the frequency of postmenopausal flashes.

Body Temperature↗
PubMed1981

Association of waking episodes with menopausal hot flushes.

To examine the possible relationship between the occurrence of menopausal hot flushes and waking episodes, a study was conducted of nine postmenopausal women with severe hot flushes and five asymptomatic premenopausal women. Measurement of simultaneous changes of finger temperature and skin resistance over the sternum was used as an objective marker of hot flushes. During cumulative sleep 47 objectively measured hot flushes occurred, and 45 were associated with a waking episode measured by polygraphic techniques. In eight of nine subjects, a significant correlation was observed between the occurrence of hot flushes and waking episodes. A similar association was not observed in premenopausal subjects. Estrogen administered to symptomatic patients resulted in significant reductions of both hot flushes and waking episodes. These data suggest the menopausal flushes are associated with a chronic sleep disturbance, and both can be improved by estrogen therapy.

Age Factors↗
PubMed1981

Effect of megestrol acetate on flushing and bone metabolism in post-menopausal women.

To avoid the risks of oestrogen therapy in post-menopausal women, we have examined the effects of a progestin, megestrol acetate (MA), on hot flushes and bone metabolism. Ten normal post-menopausal women were studied before and after the oral administration of 20, 40 and 80 mg of MA daily for 4 wk at each dose level. Finger temperature and skin resistance were recorded for 8 h as objective indices of flushing and perspiration, respectively. The fasting ratios of urinary calcium: creatinine (Ca/Cr) and hydroxyproline: creatinine (OHPr/Cr) were used as indices of bone resorption. A reduction (P less than 0.01) of flushing episodes was noted on all dose levels of MA, with 56, 11, 6 and 1 flushes occurring on 0, 20, 40 and 80 mg of medication. A decrease (P less than 0.05) of Ca/Cr was noted only with 80 mg of MA, whereas OHPr/Cr remained unchanged. We conclude that progestin therapy may provide an alternative mode of treatment for post-menopausal hot flushes. Definitive demonstration of an effect on post-menopausal bone resorption will require a long-term study of bone density.

Bone and Bones↗
PubMed1981

Effect of cimetidine on serum prolactin in normal women and patients with hyperprolactinaemia.

In normal women, intravenous injection of the H2-antihistamine, cimetidine, provoked a 3-4 fold rise in serum prolactin, without changes in serum growth hormone, thyrotrophin, or gonadotrophins. Hyperprolactinaemic patients with pituitary tumours, idiopathic hyperprolactinaemia or hypothalamic lesions demonstrated little or no rise in serum prolactin (expressed as a percentage increment) in response to cimetidine; these responses were significantly more blunted than the prolactin responses to intravenous TRH in the same subjects. Post-partum women also demonstrated blunted percentage prolactin responses to cimetidine, although responses to TRH were, in most patients, normal. Dynamic testing of prolactin secretion with cimetidine is no more useful than TRH in distinguishing tumourous from non-tumourous hyperprolactinaemia.

Adolescent↗
PubMed1981

Free estradiol in postmenopausal women with and without endometrial cancer.

To assess the role of biologically active estradiol in the development of endometrial cancer, 25 patients with endometrial tumors and a similar number of control subjects matched for age and body size were studied. No differences between the 2 groups were found for levels of total estradiol, sex hormone-binding globulin (SHBG), non-SHBG-bound estradiol, and absolute free estradiol. Body size correlated positively with levels of total, non-SHBG-bound, and absolute estradiol and negatively with SHBG levels. The obese postmenopausal women had higher total circulating levels and proportionally greater concentrations of free estradiol than nonobese subjects, suggesting a dual risk for the cellular action of circulating estradiol. These factors could contribute to the association of obesity and the occurrence of this tumor in susceptible women.

Body Weight↗
PubMed1981

Objectively recorded hot flushes in patients with pituitary insufficiency.

A study was conducted of 2 young adult women with pituitary insufficiency and complaints of hot flushes. Both underwent continuous recordings of skin temperature of the finger and skin resistance over the sternum as objective indices of flushing episodes. Frequent blood samples were also obtained during the recordings for the measurement of serum LH and FSH levels. During the 10 h of recording, 12 subjective hot flushes occurred and each was associated with a rise of finger temperature of greater than 1 C. Eighty-five percent of the temperature rises were associated with measurable decreases in skin resistance. The mean interval between flushes, the magnitude of the skin temperature and resistance changes, and the relationship of these changes to the onset of subjective flushes were identical to those observed in symptomatic postmenopausal women. Circulating gonadotropin levels were in the low to low normal range in comparison to values observed in premenopausal women and showed minimal pulsatile release. There were no significant correlations between finger temperature changes and LH levels in either subject. These results suggest that the previously described association of pulsatile LH release and the occurrence of hot flushes in postmenopausal women cannot be attributed to augmented LH secretion per se and, therefore, may be due to hypothalamic factors responsible for pulsatile LH release.

Adult↗
PubMed1981

Steroid secretion by masculinizing and "feminizing" Hilus cell tumors.

The clinical course, histology, and steroid secretion observed in two patients with hilus cell tumors are presented. One patient had signs of virilism and the other had estrogenic signs only. Steroid secretion was examined by measuring peripheral and ovarian venous gradients and pre- and postoperative levels of hormones to explain the profound differences in the biological effects exerted by the neoplasms. In the patient with virilism, the tumor's major secretory product was testosterone (T), and the dominant biosynthetic pathway was pregnenolone (Pe) leads to 17-hydroxypregnenolone leads to 17-hydroxyprogesterone leads to androstenedione (delta) leads to T. In the patient with estrogenic signs, the major secretory product was delta, derived from a similar pathway of pregnenolone leads to 17-hydroxypregnenolone leads to 17-hydroxyprogesterone leads to delta. Circulating estrone and estradiol levels were elevated, but the tumor showed limited aromatase activity, as reflected by 60- to 1500-fold larger peripheral-ovarian venous gradients of delta and T than estrone and estradiol. The high circulating estrogen levels mainly arose from the peripheral aromatization of the increased secretion of delta by the tumor. It was concluded that a similar steroidogenic pathway was employed by both tumors. The predominant secretion by the neoplasm of either T of delta was determined by the presence and the oxidation reduction equilibrium of the 17 beta-dehydrogenase enzyme. The action of this enzyme resulted in profound differences in the biological effects exerted by these tumors.

Aged↗
PubMed1981

Estrogen replacement therapy.

The use of estrogen replacement therapy in postmenopausal women is under close scrutiny. The indications and side effects of replacement therapy are reviewed, and recommendations regarding its use are made. Hot flashes, atrophy of the vaginal epithelium, and prevention of osteoporosis have been established as indications for estrogen replacement therapy. Prevention of cardiovascular disease, aging changes of skin, and the occurrence of mental illness have also been suggested as indications, but beneficial effects of estrogen replacement therapy for these problems have not been clearly established. Studies have shown that side effects of estrogen replacement therapy include endometrial cancer, hypertension, gallbladder disease, and angina pectoris. Breast cancer may also be a risk factor, but a consensus of opinion has not been established. Pulmonary embolism, cerebral vascular accident, or myocardial infarction has not been associated with estrogen replacement therapy. The use of progesterone with estrogen replacement therapy has been shown to reduce the occurrence rate of endometrial carcinoma, but it does not prevent all the actions of estrogen. Oral administration of estrogen is the preferred route despite misgivings about portal absorption and liver metabolism. Further studies must examine this question. Various agents have been shown to be effective in treating some climacteric symptoms. These include progesterone for hot flashes and calcium for the prevention of osteoporosis. Other agents may also be effective but have not been tested critically.

Aged↗