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Biomedical subjects

H L Judd

Publications and source records attributed to H L Judd.

At least 37 records · Page 2Linked to original sources
PubMed1993

The influence of luteinizing hormone and insulin on sex steroids and sex hormone-binding globulin in the polycystic ovarian syndrome.

OBJECTIVE: To examine the relationship between hyperinsulinemia, sex hormone-binding globulin (SHBG), and body mass index (BMI) on LH-induced hyperandrogenemia in patients with polycystic ovarian syndrome (PCOS). DESIGN: Insulin responses during an oral glucose tolerance test (OGTT) were assessed in 25 consecutive women with PCOS and 20 control women matched for BMI. Insulin responses and sensitivity (SI) were also determined using a frequently sampled intravenous glucose tolerance test (IVGTT). SETTING: The clinical research center at a university medical center. MAIN OUTCOME MEASURES: Serum LH, SI, and basal, peak, and area under the curve (AUC-insulin responses) were determined and correlated with SHBG, androstenedione (A), T, and free T concentrations. RESULTS: Compared with controls, the AUC-insulin response during OGTT was greater in PCOS, with an average increase of 44%. During IVGTT, AUC-insulin response was also significantly higher in PCOS versus controls, with an average increase of 53%. In addition, SI was reduced in PCOS versus controls with an average decrease of 53%. The average differences in oral- and intravenous-glucose-induced hyperinsulinemia and in insulin sensitivity between PCOS and controls were relatively constant across the entire physiological range of BMI. In PCOS, baseline LH showed strong positive correlations with baseline A and T. However, there were no significant correlations between either basal, peak, or AUC-insulin response during OGTT and IVGTT with basal T or A concentrations or between insulin and androgen levels measured at 30-minute intervals throughout the OGTT. However, basal, peak, and AUC-insulin responses during OGTT were strongly correlated with fasting SHBG binding capacity. CONCLUSIONS: These data are consistent with the hypothesis that hyperinsulinemia in PCOS influences the biologically active component of T by lowering SHBG concentrations while having little apparent impact on LH-induced secretion of androgens in vivo.

Administration, Oral↗
PubMed1993

The menopause: health implications and clinical management.

OBJECTIVE: To review the anatomy, physiology, clinical symptoms, long-term health effects, and treatment of the menopause and climacteric syndrome, with a special emphasis on features, such as incontinence, particularly relevant to geriatric medicine. DATA SOURCES: English-language publications on menopause and the climacteric. STUDY SELECTION: Articles and books containing recent information pertinent to the topics covered. Studies in human subjects were given priority, but primate studies that amplify physiologic concepts are included. DATA SYNTHESIS: Due to increased longevity, the average US woman will spend one-third of her life as a postmenopausal individual. Anatomic and physiologic changes associated with the peri- and postmenopausal state include hot flushes, genitourinary atrophy, and bone loss. Possible correlates of the menopausal transition and postmenopause include affective changes and unfavorable alterations in lipoproteins and other cardiac risk factors. Clinical correlates of these changes can include incontinence, sexual dysfunction, increased risk of fracture, dysphoric mood, and increased risk of cardiovascular disease. Formal indications for estrogen therapy are hot flushes, genital atrophy, and osteoporosis prevention; other common clinical uses are reviewed. Non-contraceptive estrogens can be administered orally, transdermally, vaginally, or by injection. Each route and preparation has some unique features with respect to actions and side effects. Progestins, in adequate doses, protect against the unwanted side effect of endometrial hyperplasia; alternatives to progestin use are presented. Non-hormonal alternatives for some peri- and postmenopausal symptoms are described. CONCLUSIONS: A discussion of the menopause and the benefits and risks of hormone therapy should be part of the routine health care of older women. Since the use of hormone therapy is elective, health care providers must elicit the goals, needs, and preferences of each patient, supply her with relevant information, and serve as a facilitator of her individual decision.

Cardiovascular Diseases↗
PubMed1993

Long-term effects of transdermal estradiol with and without medroxyprogesterone acetate.

OBJECTIVE: To study the long-term biological and metabolical effects of estradiol (E2) administered by transdermal therapeutic systems with and without the addition of medroxyprogesterone acetate (MPA). DESIGN: Open, randomized, comparative trial. SETTING: The reproductive endocrine unit of a tertiary care university-affiliated hospital. PATIENTS: Fifty-seven postmenopausal women were given E2 transdermally, whereas 28 were randomized to take MPA by mouth. Fifteen premenopausal women were studied for comparison. INTERVENTIONS: Estradiol, 0.1 mg, was administered by a transdermal therapeutic system for 24.5 of 28 days and was cycled for 96 weeks. Medroxyprogesterone acetate, 10 mg, was given for days 13 to 25 of each 28-day cycle (E+P group), whereas the remainder received E2 only. MAIN OUTCOME MEASURES: Serum E2, estrone (E1), luteinizing hormone, follicle-stimulating hormone, low-density, high-density, very low-density, and total cholesterol, triglycerides, blood pressure, renin substrate, plasma renin activity, and serum aldosterone levels were measured in all subjects at baseline and in the postmenopausal women every 24 weeks until the end of study. RESULTS: Mean +/- SE levels of E2 rose significantly from baseline at 24 weeks to 426 and 355 pmol/L for the E only and E+P groups, respectively. Smaller increases of estrone (E1) were observed to 263 and 244 pmol/L for the same respective groups. As expected, baseline levels of both gonadotropins were elevated, fell significantly with E2 administration, but remained increased in comparison with values observed in younger women. Decreases of total and low-density lipoprotein (LDL) cholesterol were observed in both groups that reached statistical significance at 48 weeks or later with the exception of LDL cholesterol in the E only group. No significant change of high-density lipoprotein or very low-density lipoprotein cholesterol or triglycerides was observed. There were reductions of mean systolic and diastolic blood pressures in both groups that reached significance at 72 weeks. Mean baseline plasma renin substrate, plasma renin activity, and serum aldosterone levels were within the ranges observed in younger, healthy women and did not change significantly with E2 administration in either group. CONCLUSION: These data support the long-term efficacy and safety of this form of replacement therapy, particularly in combination with MPA, in women with a uterus.

Administration, Cutaneous↗
PubMed1993

Effects of sodium etidronate in combination with low-dose norethindrone in patients administered a long-acting GnRH agonist: a preliminary report.

OBJECTIVE: To assess the efficacy of combining sodium etidronate with low doses of the 19-nor-testosterone progestin norethindrone or using high doses of norethindrone alone as prophylaxis against the vasomotor instability and bone density loss induced by GnRH agonists alone. METHODS: Eleven patients enrolled in this randomized study received the long-acting GnRH agonist leuprolide acetate 3.75 mg intramuscularly every 4 weeks for 24 weeks. Six patients (group I) self-administered sodium etidronate 400 mg/day orally for 14 days followed by calcium carbonate 500 mg/day orally for the next 42 days during three 56-day cycles. This regimen was supplemented by norethindrone 2.5 mg/day orally. Five patients (group II) self-administered norethindrone 10 mg/day orally. Two sets of controls were used. Group III consisted of ten previously reported patients who received the same GnRH agonist only. Group IV comprised 12 regularly cycling untreated controls. Bone mineral density, vasomotor symptoms, circulating estrogens, and lipids were assessed serially. RESULTS: The significant vasomotor instability (P < .01) and bone mineral density loss (-4.8 +/- 0.9%; P < .05) experienced by patients in group III was prevented in those in groups I and II despite maintenance of a persistent hypoestrogenic state. Bone density changes in groups I and II were similar to those in untreated controls (group IV). Persistent decreases in high-density lipoprotein (HDL) cholesterol (P = .005) and increases in the low-density lipoprotein-to-HDL ratio (P < .05) were noted only in group II patients receiving supplemental high-dose norethindrone. CONCLUSION: These preliminary data suggest that the addition of cyclic sodium etidronate in combination with low-dose norethindrone to GnRH agonists is an effective means of ameliorating the hypoestrogenic side effects induced by GnRH agonist alone.

Bone Density↗
PubMed1992

Treatment of postmenopausal osteoporosis with transdermal estrogen.

OBJECTIVE: To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures. DESIGN: Double-blind, randomized, placebo-controlled clinical trial lasting 1 year. SETTING: Referral-based outpatient clinic. PATIENTS: Seventy-five postmenopausal women, 47 to 75 years of age, with one or more vertebral fractures due to osteoporosis. INTERVENTIONS: Thirty-nine women received dermal patches delivering 0.1 mg of 17 beta-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle. Another 39 women received placebo. MEASUREMENTS: Bone turnover assessed by biochemical markers and iliac bone histomorphometry; bone loss assessed by serial measurement of bone density; and vertebral fracture rate. RESULTS: Compared with the placebo group, the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine (5.3 compared with 0.2; P = 0.007), femoral trochanter (7.6 compared with 2.1; P = 0.03), and midradius (1.0 compared with -2.6, P less than 0.001) but showed no significant difference at the femoral neck (2.6 compared with 1.4; P = 0.17). Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration (median change, -0.35 compared with 0.02 nmol/L; P less than 0.001). Histomorphometric evaluation of iliac biopsy samples confirmed the effect of estrogen on bone formation rate per bone volume (median change, -12.9 compared with -6.2% per year; P = 0.004). Also, 8 new fractures occurred in 7 women in the estrogen group, whereas 20 occurred in 12 women in the placebo group, yielding a lower vertebral fracture rate in the estrogen group (relative risk, 0.39; 95% CI, 0.16 to 0.95). CONCLUSIONS: Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis.

Administration, Cutaneous↗
PubMed1992

Is caffeine consumption a risk factor for osteoporosis?

High caffeine consumption has been proposed as a risk factor for osteoporotic fracture, but the evidence associating high caffeine intake with low bone density is inconsistent. We therefore examined the influence of caffeine consumption on bone mineral at six skeletal sites in an age-stratified random sample of white women residing in Rochester, Minnesota. After age adjustment, there was no association between overall caffeine consumption and bone mineral at five of the six sites. In the femoral shaft, however, there was a statistically significant interaction between age and caffeine consumption so that high caffeine intake was associated with slight reductions in bone mineral among elderly subjects but with modestly increased bone mineral at younger ages. When caffeine intake was categorized by source, no consistent influence of coffee, tea, or other caffeinated beverage consumption could be detected on bone mineral. Caffeine intake was, however, positively associated with cigarette smoking and alcohol consumption. After adjusting for age, caffeine consumption was not correlated with biochemical indices of bone turnover, circulating concentrations of estradiol and estrone, or other dietary and musculoskeletal variables. These data suggest that caffeine intake in the range consumed by a representative sample of white women is not an important risk factor for osteoporosis. Among elderly women, however, in whom calcium balance performance is impaired, high caffeine intake may predispose to cortical bone loss from the proximal femur.

Adult↗
PubMed1992

Gonadotropin-releasing hormone agonists: strategies for managing the hypoestrogenic effects of therapy.

Gonadotropin-releasing hormone agonists have been shown to be comparable with danazol for the treatment of endometriosis. These results are important because danazol is associated with a significant number of side effects, particularly androgenic effects, such as weight gain and acne. Although gonadotropin-releasing hormone agonists are associated with hypoestrogenic side effects, such as hot flashes and reversible bone density loss, recent studies suggest that the risk of these side effects may be modified when gonadotropin-releasing hormone agonists are combined with a progestin. These findings suggest that such regimens may further enhance the clinical usefulness of gonadotropin-releasing hormone agonist therapy for endometriosis and other estrogen-mediated diseases.

Bone Density↗
PubMed1992

Long-term administration of gonadotropin-releasing hormone agonist and dexamethasone: assessment of the adrenal role in ovarian dysfunction.

OBJECTIVE: To examine the possible impact of abnormal adrenal steroidogenesis on the ovarian dysfunction seen in polycystic ovarian disease (PCOD). DESIGN: Prospective analysis of blood sampling monthly for 6 months, then three times weekly for 90 days. SETTING: Tertiary institutional outpatient care. PARTICIPANTS: Six anovulatory women with a diagnosis of PCOD. INTERVENTION: Six-month suppression with gonadotropin-releasing hormone agonist (GnRH-a) followed by suppression with dexamethasone (DEX) for 90 days. MAIN OUTCOME MEASURES: Serum levels of testosterone (T), androstenedione (A), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), cortisol, estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and bioactive LH. RESULTS: Gonadotropin-releasing hormone agonist administration suppressed greater than 60% of the circulating levels of T and A, suggesting an ovarian origin. Minimal changes of DHEA, DHEAS, and cortisol were seen. With the addition of DEX, there was greater than 90% suppression of the total circulating A, T, DHEA, DHEAS, and cortisol, supporting the adrenal origin of the non-GnRH-a suppressible androgens. Excessive ovarian T and A secretion returned during the 90-day recovery study period in spite of rises of FSH concentrations that changed the ratio of FSH to LH in all subjects. Four of the six women failed to ovulate. In comparison of the women who did and did not ovulate during recovery, no differences in absolute levels or changes in concentrations of steroids or gonadotropins could be detected. CONCLUSIONS: Using sequential and simultaneous administration of GnRH-a and DEX, we were able to delineate the contributions of the ovaries and adrenals to the abnormal steroidogenesis seen in PCOD. Despite prolonged suppression of ovarian and then adrenal steroidogenesis, ovarian dysfunction, evidenced by abnormal androgen production, returned with cessation of agonist administration.

Adrenal Glands↗
PubMed1992

A prospective randomized comparison of luteal phase versus concurrent follicular phase initiation of gonadotropin-releasing hormone agonist for in vitro fertilization.

OBJECTIVE: To compare the effects of gonadotropin-releasing hormone agonist (GnRH-a) initiation either preceding or concurrent with controlled ovarian hyperstimulation (COH) in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). DESIGN: Fifty-five patients were prospectively randomized to receive either GnRH-a on cycle day 21 before COH until ovarian suppression was achieved (group I) or GnRH-a concurrently with COH commencing on cycle day 3 (group II). MAIN OUTCOME MEASURES: Serum gonadotropin and ovarian steroid hormone levels, as well as fertilization, spontaneous abortion, and live birth rates. RESULTS: Twenty-six patients in group I and 29 patients in group II underwent COH for IVF-ET. Patients in group II had significantly higher serum luteinizing hormone, progesterone, and testosterone levels during stimulation with human menopausal gonadotropins (hMG) before oocyte retrieval (P < 0.05). Despite similar fertilization, biochemical, and clinical pregnancy rates, the spontaneous abortion rate was higher in group II (5/6) compared with group I (1/7) (P < 0.05). Thus, the live birth rate/retrieval for group I was 6 of 24 (25%) as compared with that of group II, which was 1 of 26 (3.8%) (P < 0.05). CONCLUSIONS: The initiation of GnRH-a in the follicular phase concurrently with hMG is associated with evidence of premature luteinization, hyperandrogenemia, and poorer pregnancy outcome compared with luteal phase administration of GnRH-a before hMG for IVF-ET.

Adult↗
PubMed1992

Reduction of vasomotor symptoms and bone mineral density loss with combined norethindrone and long-acting gonadotropin-releasing hormone agonist therapy of symptomatic endometriosis: a prospective randomized trial.

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to suppress symptomatic endometriosis effectively but to elicit vasomotor symptoms and loss of bone mineral density. The role of norethindrone as a supplement to GnRHa in eliminating such side effects was assessed by enrolling 20 patients with symptomatic endometriosis diagnosed laparoscopically in a randomized, prospective, double-blinded trial. All patients received the long-acting GnRHa leuprolide acetate 3.75 mg im every 4 weeks for 24 weeks. Ten patients self-administered norethindrone 5 then 10 mg by mouth daily, whereas the remainder self-administered placebo tablets. Results of this study showed that combination therapy was as effective as GnRHa alone in significantly reducing circulating gonadotropin and estrogen levels (P less than 0.01), extent of visible endometriotic implants (P less than 0.01), and painful symptoms (P less than 0.01). Marked vasomotor and vaginal symptoms experienced by patients given GnRHa alone were minimized in those receiving GnRHa with norethindrone. Lumbar spine bone mineral density loss, measured by dual energy x-ray absorptiometry, was significantly reduced and more completely reversed in patients receiving combination therapy (P less than 0.05). A reversible decrease in high density lipoprotein-cholesterol and increase in low density lipoprotein:high density lipoprotein ratio was noted only in the patients receiving combination therapy, but not in those receiving GnRHa only. The addition of norethindrone to GnRHa is an effective means of treating symptomatic endometriosis while ameliorating side effects induced by GnRHa alone.

Bone Density↗
PubMed1992

Insulin and insulin-like growth factor-I responsiveness in polycystic ovarian syndrome.

OBJECTIVE: To assess insulin and insulin-like growth factor I (IGF-I) action in women with polycystic ovarian syndrome (PCOS). DESIGN: Hyperinsulinemia was determined by measuring the insulin responses during a 2-hour oral glucose tolerance test (OGTT). Quantification of in vivo insulin action was determined by a frequently sampled intravenous (IV) OGTT with minimal modeling analysis. In vitro sensitivity to insulin at physiological and supraphysiological concentrations and to IGF-I was assessed by examining colony formation of two hematopoietic cell populations, burst-forming units of the erythroid line (BFU-E) and human leukemia virus immortalized T-cell lines. (The proliferative responses of BFU-E, a primary tissue explant, are presumably conditioned by factors in the immediate blood-borne environment, whereas proliferative responses of T-cell lines are presumed to reflect intrinsic target-cell hormone sensitivity.) SETTING: Tertiary care research institution. PATIENTS: Eight patients (4 obese and 4 nonobese) with PCOS and three healthy women for reference controls. RESULTS: Nonobese (P less than 0.04) and obese patients with PCOS (P less than 0.01) both demonstrated significant hyperinsulinemia after OGTT. In vivo insulin resistance was observed in both nonobese (P less than 0.03) and obese PCOS subjects (P less than 0.01) using frequently sampled IV OGTT. Both nonobese (P less than 0.03) and obese patients with PCOS (P less than 0.01) had blunted in vitro clonal responses of BFU-E, with normal T-cell line clonal responsiveness to physiological levels of insulin and normal BFU-E and T-cell line clonal responses to IGF-I. CONCLUSIONS: These findings demonstrate the following in both nonobese and obese patients with PCOS: (1) there is in vivo hyperinsulinemia and resistance to insulin action on glucose disposal; (2) with BFU-E, there is in vitro resistance to the mitogenic action of insulin but normal responsiveness to IGF-I; and (3) there is normal in vitro mitogenic responsiveness of T-cell lines to both insulin and IGF-I. The intrinsically normal mitogenic responsiveness to insulin and, especially to IGF-I, whether or not under the influence of the bloodborne milieu, provides a mechanism whereby hyperinsulinemia could directly contribute to the ovarian abnormalities that characterize PCOS.

Adult↗
PubMed1992

Menopause: new indications and management strategies.

Postmenopausal women may benefit from estrogen replacement. In addition to the well-established treatment indications of vasomotor symptoms, genitourinary atrophy, and osteoporosis, studies also suggest improvement in psychologic well-being and prevention of coronary heart disease. The potential cardioprotective effects of estrogen do not appear to be solely from alterations in lipid metabolism. Major risks of estrogen replacement including breast cancer continue to be a concern. Strategies of management including continuous estrogen and progestin regimens are reviewed. There exists an increasing body of evidence that successful treatment for estrogen-dependent tumors including endometrial carcinoma is not a contraindication to estrogen replacement therapy. The potential use of tamoxifen to relieve symptoms and prevent bone loss in women with breast cancer is suggested.

Affect↗
PubMed1992

Long-term transdermal estradiol therapy: effects on endometrial histology and bleeding patterns.

Sixty postmenopausal women were enrolled in a 2-year randomized unmasked trial to determine the long-term safety of estradiol (E2) administration by a transdermal therapeutic system. Group I subjects received 0.1 mg of transdermal E2 for 24.5 days of each 28-day cycle for 96 weeks. Group II subjects received the same dosage of transdermal E2 plus 10 mg of medroxyprogesterone acetate, given orally from days 13-25 of each cycle. Vaginal bleeding patterns and endometrial histology were characterized. The subjects recorded bleeding patterns daily. Endometrial biopsies were performed during scheduled follow-up visits at 48 and 96 weeks or as needed to evaluate abnormal bleeding. Data were analyzed by intention to treat. Ten and four subjects dropped out of the study from groups I and II, respectively. A total of 575 and 627 treatment cycles were observed in the same respective groups. Vaginal bleeding was observed in 980 cycles: 381 of 575 cycles in group I (66.3%) and 599 of 627 cycles in group II (95.5%). Bleeding onset, duration, and quantity were similar for both groups. The incidence of hyperplasia was 42 and 4% for groups I and II, respectively, over the 96-week study period. All cases of hyperplasia in group I were treated with sequential medroxyprogesterone acetate for 12 weeks, followed by rebiopsy. In ten of 11 cases, the progestin therapy converted the hyperplasia to a normal endometrium. In one case, the endometrium became hyperplastic again at 96 weeks, but reverted to normal with 12 weeks of medroxyprogesterone acetate.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1991

Comparison of continuous versus sequential estrogen and progestin therapy in postmenopausal women.

A pilot study was performed comparing the efficacy and safety of continuous versus sequential schedules of the two most commonly prescribed medications for ovarian hormone replacement, conjugated equine estrogens and medroxyprogesterone acetate. Bleeding patterns, endometrial histology, and metabolic parameters were studied in 48 postmenopausal women prospectively randomized to a continuous schedule (daily estrogen and progestin) or a sequential schedule (conjugated estrogen on days 1-25, medroxyprogesterone acetate on days 16-25). Doses studied were 0.625 and 1.25 mg of conjugated estrogens and 10 mg of medroxyprogesterone acetate. Significantly greater bleeding was observed with the 1.25-mg dosage of conjugated estrogens. Bleeding patterns were similar between schedules, with the exception that amenorrhea was more prevalent in the women using the 1.25-mg dosage of estrogen and the continuous progestin schedule. More frequent endometrial atrophy was observed with the continuous schedule, supporting the concept that prolonged use of this schedule may promote amenorrhea in most patients. Both doses and schedules were associated with modest and insignificant increases in high-density lipoprotein cholesterol. Sequential therapy did not prevent the estrogen-induced decrease of low-density lipoprotein cholesterol, whereas the continuous schedule did, particularly with 0.625-mg dosage of conjugated estrogens. Significant increases of triglycerides were also seen with the continuous but not with the sequential schedule. Because of reports that the continuous schedule using the 2.5-mg dosage of medroxyprogesterone acetate does not elicit these actions on circulating lipids, attention should be directed toward examining the long-term effects of this lower dosage given continuously.

Drug Administration Schedule↗
PubMed1991

No acute effect of physiological insulin increase on dehydroepiandrosterone sulfate in women with obesity and/or polycystic ovarian disease.

Conflicting information concerning the acute effect of hyperinsulinemia on circulating adrenal androgens, specifically DHEAS, is available. The effect of PCOD or obesity on this response is unclear. We prospectively examined the acute response of circulating DHEAS to the physiological rise in serum insulin after an OGTT in 10 women with PCOD (5 obese and 5 normal weight) and 10 ovulatory euandrogenic women (5 obese and 5 normal-weight). All underwent a standard 75-g 2-hour OGTT. Insulin and DHEAS were measured before and after OGTT. To control for the potential dilutional effects induced by hyperinsulinemia or hyperglycemia on intravascular tonicity, DHEAS levels were correlated to serum protein. As expected, the 2-hour insulin levels were significantly greater than baseline. No significant changes in circulating DHEAS or in the DHEAS to protein ratio was observed in any patient group 2 hours after glucose-induced hyperinsulinemia. The power of this study was greater than 89% for an alpha error of 0.05 and an expected change in DHEAS of 25%. In summary, it appears unlikely that acute increases in insulin within the physiological range are important in the regulation of circulating DHEAS in either PCOD or euandrogenic women, independent of obesity.

Administration, Oral↗
PubMed1991

Induction of hypothalamic opioid activity with transdermal estradiol administration in postmenopausal women.

The effects of estradiol (E2) administered by a transdermal system on the induction of hypothalamic opioid activity was examined in 18 postmenopausal women. Women were given 25, 50, 100, or 200 micrograms/d dosages of E2 for 28 days each. Naloxone at a dosage of 2 mg/h was infused intravenously for 4 hours, and serum was obtained every 15 minutes for 6 hours. With increasing doses, rises of serum E2 and estrone were elicited across the range seen in premenopausal women. A stepwise reduction of luteinizing hormone (LH) levels was observed with increasing dosages of E2. The naloxone infusions resulted in significant increases of LH when E2 was being given but not during the pretreatment studies. These data indicate E2, in physiological concentrations, induces hypothalamic opioid activity.

Administration, Cutaneous↗
PubMed1990

Relationship between serum intact parathyroid hormone concentrations and bone remodeling in type I osteoporosis: evidence that skeletal sensitivity is increased.

To define the role of parathyroid gland function in the pathophysiology of bone loss in type I (postmenopausal) osteoporosis, we measured serum intact parathyroid hormone (PTH) concentration by immunoradiometric assay (IRMA) and by multisite immunochemiluminometric assay (ICMA) in 63 postmenopausal osteoporotic women (PMOp) with vertebral compression fractures and in 75 age-comparable postmenopausal normal women (PMNl). Also, tetracycline-based histomorphometric indices in cancellous bone were assessed in iliac biopsy samples from 61 PMOp and 28 PMNl women. Serum PTH concentrations by IRMA were similar in PMOp and PMNl (medians, 3.92 and 3.77 pmol/l; NS) but were significantly lower in PMOp by the more sensitive ICMA (medians, 2.82 and 3.14 pmol/l; P less than 0.01). By multiple linear regression analysis, serum PTH was directly related (P less than 0.001) to activation frequency, bone resorption rate, bone formation rate, and the calculated rate of bone loss. For each unit (pmol/l) increase in serum PTH by ICMA, activation frequency increased by 1.3%/year more (P = 0.01), bone resorption rate increased by 3.9%/year more (P = 0.003), and the rate of cancellous bone loss was 2.8% greater (P = 0.0003) in the PMOp women compared with the PMNl women. Concentrations of serum estradiol, but not serum estrone, had a weak opposing effect to PTH, especially for bone formation rate. These data suggest that in PMOp the bone has increased sensitivity to the biologic effects of PTH. This may represent one of the fundamental pathophysiologic defects in PMOp and, in the setting of estrogen deficiency, may explain, in part, their greater rate of bone loss.

Aged↗