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Biomedical subjects

H L Judd

Publications and source records attributed to H L Judd.

At least 55 records · Page 3Linked to original sources

The effects of combining norethindrone with a gonadotropin-releasing hormone agonist in the treatment of symptomatic endometriosis.

Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRH-a) is associated with side effects secondary to the induced hypoestrogenic state. In an effort to ameliorate these symptoms, 10 patients with symptomatic endometriosis self-administered the GnRH-a [D-His6(Imbzl)-Pro9-NET]-GnRH in combination with norethindrone daily for 24 weeks. Painful symptoms were significantly suppressed after therapy (P less than 0.005). Objective review of photographs taken at laparoscopy before and after therapy demonstrated significant reduction of visible implants (P less than 0.005). Vasomotor symptoms were minimized when compared with a group of 16 patients previously treated with GnRH-a alone. Bone mineral density of the distal radius assessed by single photon absorptiometry was not reduced during therapy, although lumbar spine bone density assessed by quantitative computerized tomography was minimally but reversibly reduced. No metabolic derangements were detected. The combination of norethindrone with GnRH-a is a well tolerated and effective means of treating symptomatic endometriosis.

Adult↗

Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist plus medroxyprogesterone acetate.

Highly potent agonists of gonadotropin-releasing hormone (GnRH) have been shown to reduce pelvic pain due to endometriosis and the size and number of implants seen at laparoscopy. The accompanying symptoms and problems associated with the hypoestrogenism induced by the agonist have reduced its acceptability and raised questions about its safety. In an attempt to optimize this form of therapy, we treated eight women with endometriosis with daily subcutaneous injections of a potent agonist of GnRH plus a daily oral dose of 20-30 mg of medroxyprogesterone acetate for 24 weeks. Ovarian estrogen secretion was reduced to levels seen in castrated women throughout the course of treatment. Markers of hypoestrogenism, such as hot flashes and loss of calcium from bone, were diminished with this regimen compared with previous findings with GnRH agonist alone. Blinded evaluation of laparoscopic photographs failed to reveal improvement or suppression of active endometriosis. The results of this pilot study indicate that the addition of medroxyprogesterone acetate decreases the hypoestrogenic effects of GnRH agonist alone but fails to affect pain or endometriotic implants.

Adult↗

Effects of gonadotropin-releasing hormone (GnRH) agonist on pituitary and ovarian responses to pulsatile GnRH therapy in polycystic ovarian disease.

Nine clomiphene citrate-resistant polycystic ovarian disease (PCOD) patients received intravenous gonadotropin-releasing hormone (GnRH) pulses before and immediately after 1 month of GnRH agonist (GnRH-a) therapy. Circulating gonadotropin and ovarian steroid levels, as well as follicular development, were measured throughout therapy. Results were compared with those obtained from five hypogonadotropic patients treated with GnRH pulses only who ovulated during six of seven treatment cycles. Only two PCOD patients ovulated normally with GnRH pulses before GnRH-a therapy. Aberrant gonadotropin and ovarian steroid secretory patterns were noted in the others. After GnRH-a, gonadotropin and ovarian steroid hormone levels were similar to those of the hypogonadotropic patients. Subsequent secretory responses to GnRH pulses were partially normalized. However, only two additional PCOD patients ovulated.

Amenorrhea↗

Recovery of hormone secretion after chronic gonadotropin-releasing hormone agonist administration in women with polycystic ovarian disease.

Persistent suppression of gonadotropin and ovarian steroid production can be achieved in women with polycystic ovarian disease (PCO) by daily administration of a long-acting GnRH agonist (GnRHa). This study was designed to determine the patterns of recovery of clinical responses and hormonal secretion after chronic GnRHa administration in women with PCO. Six women with PCO were treated with daily sc injections of [D-His6(imBzl),Pro9-NEt]GnRHa (100 micrograms) for 6 months. Blood samples were obtained at the time of and three times weakly for 90 days after discontinuation of agonist therapy. In five women who did not ovulate, the suppressed serum FSH levels rose to pretreatment values within 10 days. In contrast, a gradual and progressive increase in serum LH (as measured by bioassay and immunoassay) was apparent by day 18. The LH increase coincided with progressive increases in serum estrone (E1), androstenedione, and testosterone. Serum estradiol (E2) began to rise on day 28. All hormones returned to their pretreatment baseline values within the 90-day recovery interval, with the exception of E2. Trend analysis of the slopes of recovery revealed that the incremental secretion patterns of E1, E2, androstenedione, and testosterone differed significantly from that of FSH, but not from those of bioactive or immunoactive LH. Serum progesterone, dehydroepiandrosterone sulfate, and cortisol did not change after withdrawal of GnRHa. One woman ovulated spontaneously on day 52 before which her hormone secretion patterns were indistinguishable from those of the other women. In summary, 1) during recovery after discontinuation of chronic GnRH agonist therapy the patterns of FSH and LH release suggested resumption of endogenous GnRH action on the pituitary with greater release of FSH than LH, a pattern that would be expected in the absence of ovarian steroid influence; 2) the lack of early estrogen production despite the increase in serum FSH concentrations suggests inadequate FSH secretion, abnormal ovarian responsiveness to FSH, or impaired FSH bioactivity; 3) androgen secretion was provoked by the increase in LH secretion; 4) per unit LH measured by bioassay, greater ovarian androgen secretion was stimulated in PCO than ovulatory women; and 5) the likelihood of spontaneous ovulation during recovery was minimal.

Adult↗

Prediagnostic serum hormones and the risk of prostate cancer.

Serum samples were obtained from 6860 men during their study examination from 1971 to 1975. After a surveillance period of about 14 years, 98 incident cases of prostate cancer were identified. Their stored sera and that of 98 matched controls from the study population were tested for the following: testosterone, dihydrotestosterone, estrone, estradiol, and sex hormone globulin. There was a suggestion that serum dihydrotestosterone levels were lower and the testosterone/dihydrotestosterone ratios were higher in the prostate cancer cases compared with their controls. However, none of these associations or that of the other hormones was strongly significant. Further work is needed to clarify the relationship between sex hormones and prostate cancer risk.

Estrogens↗

Preoperative localization of androgen-secreting tumors: clinical, endocrinologic, and radiologic evaluation of ten patients.

A series of 10 patients with benign androgen-secreting neoplasms is presented. Nine tumors were ovarian, and one adrenal. In an attempt to correctly diagnose the presence of tumor and to accurately localize the lesion to a specific gland, steroid hormones in peripheral, ovarian, and adrenal vein serum were analyzed by radioimmunoassay. Little correlation was made in this series with those levels of testosterone (greater than 2 ng/ml) or dehydroepiandrosterone sulfate (greater than 7000 ng/ml) that have been widely used to predict the presence of such tumors. Peripheral testosterone levels were less than 2 ng/ml in 50% of our patients, and the dehydroepiandrosterone sulfate level was greater than 7000 ng/ml in only a single patient with an ovarian lipoid cell tumor. Pelvic ultrasonography was found to be of limited value in evaluating nonpalpable tumor because of the small size (less than 2 cm3) of the majority of these neoplasms. The use of selective retrograde venous catheterization to demonstrate significant effluent-peripheral vein androgen gradients served to accurately localize androgen-secreting tumors in all six patients in which it was used. Our data emphasize the potential pitfalls that exist in the preoperative evaluation of patients with these fascinating neoplasms and the importance of a high degree of suspicion on the part of the physician caring for these women.

Adrenal Gland Neoplasms↗

TeBG- and CBG-bound steroid hormones in rabbits are available for influx into uterus in vivo.

The metabolic clearance rate (MCR) of gonadal or adrenal steroid hormones in rabbits often does not bear the expected inverse relationship with hormone binding to testosterone-binding globulin (TeBG) or corticosteroid-binding globulin (CBG). This suggests TeBG or CBG may not impede steroid hormone delivery to tissues. The effects of rabbit plasma proteins on the influxes of 3H-labeled steroids from the circulation into the rabbit uterus were measured in vivo using a tissue sampling single-injection technique. In the absence of plasma proteins, estradiol (E2) and testosterone (T) were freely diffusible through the uterine microvasculature (i.e., extraction greater than 80%). The extractions of dihydrotestosterone (DHT) and corticosterone (B) ranged from 60 to 72%, while that of cortisol (F) was reduced at 40%. Rabbit serum exerted no inhibition of the influxes of the steroids tested. The influxes of T and B greatly exceeded the rates that would be expected if only the free and albumin-bound fractions estimated in vitro were diffusible in vivo. However, the extraction of [3H]corticosteroid-binding globulin or bovine [3H]albumin were low, consistent with little, if any, extravascular uptake of the plasma proteins. The results indicate both albumin-bound and globulin-bound steroid hormone are available for transport into the uterus in the rabbit in vivo without significant exodus of the plasma protein, per se.

Animals↗

New issues in geriatric care.

The rapid growth of the elderly population has increased the need for improved geriatric care and prevention of disability. For example, the prevalence and severity of osteoporosis can be reduced significantly by the use of estrogen, with or without added progestin, in postmenopausal women. A common and devastating problem of frail elderly persons is urinary incontinence, most cases of which can be classified without referral for urologic services. Appropriate treatment can improve nearly half of all cases of persistent incontinence. Comprehensive geriatric assessment is effective in guiding the treatment of frail elderly patients and leads to significantly improved outcomes under appropriate conditions. The advent of the teaching nursing home has shed light on the medical problems of elderly residents of nursing homes, including malnutrition, dysregulation of water and electrolyte balance, falling, cognitive and affective illnesses, behavior disturbances, infections, and pathogenic drug use. The future application of advanced technology may revolutionize nursing home care.

Aged↗

Blood coagulation in postmenopausal women given estrogen treatment: comparison of transdermal and oral administration.

The responses of the blood coagulation and related systems were studied in 23 postmenopausal women, all of whom received, in randomized order, therapy with conjugated oral estrogens (0.625 and 1.25 mg daily) and transdermally administered estradiol in doses of 25, 50, 100, and 200 micrograms/24 hr. Neither plasma fibrinopeptide A determinations nor plasma fibrinogen chromatographic findings were altered; thus there is no evidence of accelerated fibrinogen turnover with either form of therapy. However, alpha 1-antitrypsin and plasminogen concentrations were significantly increased with the higher dosage of oral but not with transdermally administered estrogen. Similarly, ceruloplasmin concentration was significantly elevated with both oral doses but was unchanged by transdermal therapy.

Administration, Cutaneous↗

Selective availability of protein bound estrogen and estrogen conjugates to the rat kidney.

Estrogen glucuronides are selectively cleared by the kidney as compared to estrogen sulfates. The selective trafficking of circulating serum estrogen conjugates to kidney and urine may arise from differential transport properties of the various estrogen conjugates in the renal microcirculation. In the present study, the effects of glomerular and peritubular permeability barriers, and plasma protein binding on the influx of unconjugated and conjugated estrogens into rat kidney were studied. Experiments were carried out utilizing an in vivo double isotope, single injection, timed tissue sampling technique. The extractions of these steroids by the renal cortex were examined utilizing inulin as the reference substance, as it is freely permeable through the glomerular and tubular capillary permeability barriers, but not extracted by tubular epithelial cells. The method was validated by studying the extraction of para-amino hippuric acid (PAH) before and after probenecid treatment. In the absence of plasma proteins, all the estrogens and estrogen conjugates readily diffused through both the glomerular and peritubular capillary permeability barriers and were extracted by tubular epithelia. The addition of 4% albumin to the injection solution led to significant inhibitions of extraction of estradiol (E2) and estrone sulphate (E1-S) only. The extraction of E1-S was reduced to a value less than that of inulin; the extraction of E2 was less than that of control value but significantly more than that of inulin. The addition to the injection solution of human pregnancy sera containing sex hormone binding globulin and albumin was associated with a reduction in the extraction of all estrogens and estrogen conjugates except estriol and E1-S to values approximating that of inulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Hyperemesis gravidarum in relation to estradiol levels, pregnancy outcome, and other maternal factors: a seroepidemiologic study.

Two studies were conducted to assess factors associated with increased risk of hyperemesis gravidarum during pregnancy with data and serum samples collected from participants in the Collaborative Perinatal Study. In the case-control study, 419 pregnant women with hyperemesis gravidarum were matched on medical center, date of study registration, and race with 836 pregnant women who did not vomit during the index pregnancy. Younger age, nulliparity, and high body weight were significantly associated with increased risk of hyperemesis. Women with hyperemesis had significantly reduced risk of fetal loss; however, their infants had higher risk of central nervous system malformations. In the second study, first-trimester pregnancy hormones were measured in the serum of 35 women with hyperemesis and 35 control women who were individually matched to cases on age, parity, and medical center. After adjusting for length of gestation, mean levels of total estradiol were 26% higher and mean levels of sex hormone binding-globulin binding capacity were 37% higher in patients with hyperemesis gravidarum than in control subjects. These differences were statistically significant. Although human chorionic gonadotropin concentrations were higher in control pregnancies, the differences were not statistically significant. The average amount of estradiol that was nonprotein bound (adjusted for length of gestation) was also higher in patients than in control subjects. These results are consistent with the hypothesis that elevated estrogen levels are responsible for excessive vomiting in pregnancy.

Adult↗

The effects of membrane permeability and binding by human serum proteins on steroid influx into the rabbit uterus.

The effects of capillary membrane permeability and binding by human plasma proteins on the influxes of tritium-labeled steroids from the circulation into the uterus were measured in vivo in anesthetized rabbits with a tissue-sampling, single injection technique, and the results were compared with similar studies involving rats. Rabbits were used in this study because this species, unlike the rat, has a sex steroid-binding protein. The impact of capillary membrane permeability markedly varied with different steroids and did not completely parallel the lipid solubility of these compounds. The addition of plasma proteins to the injection vehicle had varied inhibitory effects on the in vivo extractions by the uterus. These in vivo extraction values could not be predicted from in vitro studies of steroid binding to plasma proteins and the results underscore the importance of performing in vivo studies so that we may have a better understanding of the bioavailability of steroids to tissues.

Animals↗

Suppression of the ovary using a gonadotropin releasing-hormone agonist prior to stimulation for oocyte retrieval.

Five women with prior suboptimal ovarian stimulation for in vitro fertilization and embryo transfer (IVF-ET) were pretreated with a long-acting gonadotropin-releasing hormone (GnRH) agonist beginning in the midluteal phase of the preceding menstrual cycle. The four women with normal luteal function had castrate estrogen levels following regression of the corpus luteum, whereas one woman with an abnormal luteal phase and perimenopausal levels of gonadotropins had an agonistic response. In the three women with adequate stimulation, 20 oocytes were obtained and one women became pregnant. Initiation of GnRH agonist therapy during the luteal phase of a normal menstrual cycle may be an efficient way of obtaining ovarian suppression without an agonistic response.

Embryo Transfer↗

Oestrogen replacement therapy: physiological considerations and new applications.

The total impact of the menopause on the health of women and the ultimate benefit/risk ratio of oestrogen replacement therapy are yet to be defined completely. Until these are accomplished, broad general guidelines for the use of oestrogen replacement therapy in all patients cannot be given. Treatment should be individualized to the patient's specific needs. Use of appropriate dosages of oestrogen in combination with progestin administration should reduce risk and enhance benefits for those subjects requiring its use. The development of new non-oral methods of administration should also help.

Breast Neoplasms↗

Dietary calcium intake and rates of bone loss in women.

We measured bone mineral density (BMD) at the midradius and lumbar spine in 106 normal women, ages 23-84 yr (61 were postmenopausal). Three to nine measurements (median, four) were made over 2.6 to 6.6 yr (mean, 4.1 yr). The correlation between calcium intake (range, 260-2,035 mg/d) and rate of change in BMD was not significant at the midradius (r = 0.06) or lumbar spine (r = 0.08), even after adjusting for age, menopausal status, and serum estrogen levels by multiple regression analysis. Women in the lower (mean, 501 mg/d) and in the upper (mean, 1,397 mg/d) quartiles of dietary intake had similar rates of change in BMD (%/yr [mean +/- SE], at midradius, -0.78 +/- 0.24 and -0.91 +/- 0.17 for lower and upper quartiles, respectively; at lumbar spine, -1.06 +/- 0.24 and 0.98 +/- 0.24). These data do not support the hypothesis that insufficient dietary calcium is a major cause of bone loss in women.

Adult↗

Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease.

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic GnRHa administration results in apparently complete persistent suppression of ovarian steroid secretion; 2) adrenal steroid secretion is not influenced directly or indirectly; and 3) its use may be helpful in the treatment of endometrial hyperplasia and ovarian androgen excess in women with PCO.

Androgens↗

Treatment of endometriosis with a long-acting gonadotropin-releasing hormone agonist.

Sixteen women with endometriosis were treated with daily subcutaneous injections of a potent agonist of gonadotropin-releasing hormone (GnRH) for six months. Ovarian estrogen secretion was reduced to castrate levels during most of the course of treatment. Blinded evaluation of laparoscopic photographs confirmed marked suppression of visually apparent disease, but biopsy specimens showed occult, inactive endometriosis in most cases. Marked pain relief was noted by all patients. As a result of this "medical oophorectomy," the women experienced severe hot flashes, and many had insomnia and emotional disturbances. Vaginal cytology showed menopausal changes but related symptoms were generally mild. Calcium excretion rose to menopausal levels. High-density lipoprotein and total cholesterol remained unchanged. These results indicate that GnRH agonist administration has impressive effects on endometriotic implants, and these actions may be enhanced with longer therapy. Further development of this new form of therapy should involve either use of lesser degrees of ovarian suppression or adjunctive therapy to counter the side effects of "medical oophorectomy."

Adult↗