Combined effects of Hurricane Katrina and Hurricane Gustav on the mental health of mothers of small children.

Few studies have assessed the results of multiple exposures to disaster. Our objective was to examine the effect of experiencing Hurricane Gustav on mental health of women previously exposed to Hurricane Katrina. A total of 102 women from Southern Louisiana were interviewed by telephone. Experience of the hurricanes was assessed with questions about injury, danger and damage, while depression was assessed with the Edinburgh Depression Scale and post-traumatic stress disorder using the Post-Traumatic Checklist. Minor stressors, social support, trait resilience and perceived benefit had been measured previously. Mental health was examined with linear and log-linear models. Women who had a severe experience of both Gustav and Katrina scored higher on the mental health scales, but finding new ways to cope after Katrina or feeling more prepared was not protective. About half the population had better mental health scores after Gustav than at previous measures. Improvement was more likely among those who reported high social support or low levels of minor stressors, or were younger. Trait resilience mitigated the effect of hurricane exposure. Multiple disaster experiences are associated with worse mental health overall, although many women are resilient. Perceiving benefit after the first disaster was not protective.

Serum human chorionic gonadotropin levels are correlated with body mass index rather than route of administration in women undergoing in vitro fertilization--embryo transfer using human menopausal gonadotropin and intracytoplasmic sperm injection.

OBJECTIVE: To compare subcutaneous (SC) and intramuscular (IM) hCG administration and their association with body mass index (BMI) in women undergoing IVF-ET using hMG and ICSI. DESIGN: Prospective, randomized controlled trial. SETTING: Private infertility clinic. PATIENT(S): Twenty-one ovulatory women, 29-39 years, were enrolled. Treatment of one patient who failed to respond to hMG was canceled. INTERVENTION(S): A standard IVF-ET treatment plan using an initial dose of 300 U of hMG was followed. Patients were randomly assigned to receive 10,000 IU hCG, either IM in the gluteal region or SC in the lower abdomen. Exactly 12 hours later, serum for hCG determination was obtained. All oocytes were fertilized using ICSI technology. MAIN OUTCOME MEASURE(S): Human chorionic gonadotropin levels 12 hours after injection, BMI, and oocyte maturity. RESULT(S): No significant differences in hCG levels were found, with mean levels of 225 +/- 24 mIU/mL for SC injection versus 213 +/- 26 mIU/mL for IM injection. No differences were observed in the percentage of mature oocytes. A significant negative correlation was found between BMI and hCG levels in all patients, regardless of route of administration. CONCLUSION(S): The highest levels of hCG were measured in women with the lowest BMI. Patients' body size, rather than route of hCG delivery, appears to determine circulating levels of hCG.

Pregnancy after treatment with the insulin-sensitizing agent troglitazone in an obese woman with the hyperandrogenic, insulin-resistant acanthosis nigricans syndrome.

OBJECTIVE: To report a case of unassisted pregnancy after 5 months of troglitazone treatment in a severely hyperandrogenic, insulin-resistant woman with acanthosis nigricans (HAIR-AN) previously managed with depot leuprolide acetate (LA) plus oral contraceptive and dexamethasone therapy. DESIGN: Case report. SETTING: Private infertility clinic. PATIENT(S): A 28-year-old African-American woman with excessive obesity (body mass index = 42 kg/m2) and HAIR-AN syndrome. INTERVENTION(S): Androgen suppression with depot LA plus oral contraceptive and dexamethasone therapy, troglitazone treatment resulting in normalization of fasting insulin and testosterone, spontaneous menses, and an unassisted pregnancy. MAIN OUTCOME MEASURE(S): Luteinizing hormone and testosterone concentrations, fasting insulin and glucose levels, insulin-glucose ratios, hCG levels, and ultrasound examinations. RESULT(S): Spontaneous menses followed by an intrauterine pregnancy after 5 months of treatment with troglitazone, an insulin-sensitizing agent, in a woman with severe HAIR-AN syndrome whose hyperandrogenism previously could be normalized only with depot LA plus oral contraceptive therapy and dexamethasone. CONCLUSION(S): Troglitazone treatment resulted in attenuation of both hyperinsulinemia and hyperandrogenism in an obese woman with HAIR-AN and resulted in resumption of menses and a spontaneous pregnancy.

Postmenopausal dehydroepiandrosterone administration increases free insulin-like growth factor-I and decreases high-density lipoprotein: a six-month trial.

OBJECTIVE: To determine the effect of administering 6 months of oral postmenopausal DHEA therapy on serum DHEA, DHEAS, and T levels and on physiologic endpoints including lipoproteins and insulin-like growth factor-I (IGF-I). DESIGN: Randomized, double-blind, parallel trial. SETTING: Academic referral practice. PATIENT(S): Thirteen normal-weight or overweight, healthy, nonsmoking, postmenopausal women. INTERVENTION(S): Administration of oral micronized DHEA (25 mg/d). MAIN OUTCOME MEASURE(S): Monthly fasting 23 hours postdose levels of serum DHEA, DHEAS, T, lipoproteins, IGF-I, IGF binding protein-3 (IGFBP-3), and liver function tests. Morphometric indices by dual-energy x-ray absorptiometry scan (percent body fat; lean body mass), immune indices, and insulin sensitivity. RESULT(S): Levels of DHEA, DHEAS, and T all rose into premenopausal ranges, but after 6 months, levels of DHEA and T did not differ from baseline or placebo. At 3 months, the ratio of IGF-I to IGFBP-3 rose by 36.1% +/- 12.7%, but it fell to placebo values by 6 months. High-density lipoprotein and apolipoprotein A1 levels declined. CONCLUSION(S): Patients appeared to tolerate 6 months of DHEA therapy well. Given the small study size, no statistically significant differences in morphometric indices, immune indices, or insulin-sensitizing properties were observed, but significant attenuation of bioavailability occurred. Supplementation with DHEA increased IGF-I/IGFBP-3 levels at 3 months and decreased high-density lipoprotein and apolipoprotein A1 levels at 6 months.

Effect of postmenopausal estrogen replacement on circulating androgens.

OBJECTIVE: To determine the effect of estrogen replacement therapy (ERT) on serum androgen levels in postmenopausal women. METHODS: We measured serum dehydroepiandrosterone (DHEA), DHEA-sulfate, testosterone, estradiol (E2), LH, FSH, and sex hormone binding globulin in 8:00 AM fasting serum samples from a previous randomized, blinded, placebo-controlled crossover study in which 28 postmenopausal women (27 naturally menopausal) were given 2 mg/day of oral micronized estradiol. The treatment arms were 12 weeks with a 6-week washout. RESULTS: Estrogen replacement therapy raised mean (+/- standard error of the mean [SEM]) serum E2 from 8.7 +/- 1.0 to 117 +/- 18.7 pg/mL (P < .001 from baseline). Concurrently, mean (+/- SEM) DHEA-sulfate fell from 67.3 +/- 9.6 to 52.1 +/- 6.4 micrograms/dL (P < .001), and mean (+/- SEM) testosterone fell from 16.1 +/- 2.4 to 9.4 +/- 1.4 ng/dL (P = .006). Both FSH and LH declined significantly. Sex hormone binding globulin increased by 160% with ERT (P < .001). CONCLUSION: Menopausal ERT decreases serum androgen levels, decreasing DHEA-sulfate and testosterone by 23% and 42%, respectively. Whereas the decline in testosterone is likely due to decreased LH-driven ovarian stromal steroidogenesis, the declining levels of DHEA-sulfate also may imply a direct adrenal effect of estrogen. Bioavailable testosterone likely is reduced even more profoundly because sex hormone binding globulin is increased 160% by estrogen. Thus, menopausal ERT may induce relative ovarian and adrenal androgen deficiency, creating a rationale for concurrent physiologic androgen replacement.

Oral contraceptive therapy for polycystic ovary disease after chronic gonadotropin-releasing agonist administration. Predictors of continued ovarian suppression.

OBJECTIVE: To study the beneficial effects of oral contraceptive (OC) therapy following gonadotropin-releasing hormone agonist (GnRH-a) administration in women with polycystic ovary disease (PCOD). STUDY DESIGN: Twenty-three hyperandrogenic women (aged 15-39) were randomized into two groups; GnRH-a (depot every 28 days) for six months or combination therapy (GnRH-a plus OC "addback") for six months. Following six months of treatment with either therapy, all patients received OC therapy for at least six months. The hormonal state was evaluated at three-month intervals. RESULTS: Hormone levels of luteinizing hormone (LH), testosterone (T) and free T remained suppressed within the normal range in 11 of 17 patients (65%) during the six months of OC only therapy, while the other six patients showed "escape" from suppression, with the LH, T and free T concentrations rising to pre-GnRH-a treatment levels. Use of OC addback therapy did not potentiate the long-acting therapeutic effect of GnRH-a pretreatment; three of six patients in the escape group were pretreated with combination therapy and three with GnRH-a only. CONCLUSION: In the majority of women with PCOD, OC therapy following GnRH-a administration was effective in maintaining ovarian androgen suppression. Failure to maintain ovarian suppression in this patient population was associated with higher elevations of baseline free T concentrations.

PIP: Clinical investigators randomly allocated 24 hirsute women aged 15-39 years with polycystic ovary disease (PCOD) to either the treatment program offering an injection of leuprolide acetate (a highly potent gonadotropin-releasing hormone agonist [GnRH-a]) for depot suspension (3.75 mg) at 28-day intervals for six months or the treatment program offering both the same injection and a combined oral contraceptive (OC) as add-back for six months. At three months, one woman moved out of state and withdrew from the study. After six months of either GnRH-a treatment regimen, all remaining 23 women received only OCs for six more months. Six women did not successfully complete the OC therapy and were excluded from the statistical analyses. The investigators aimed to examine the benefits of OC use in the management of women with PCOD after six months of pretreatment with the GnRH-a. During the OC-only treatment period, 11 (65%) of 17 patients still had suppressed levels of luteinizing hormone (LH), testosterone (T), and free T within the normal range. These levels increased to pre-GnRH-a treatment levels in the remaining six women, indicating escape from ovarian suppression. Three of six women in the escape group received combination therapy for pretreatment, while the other three received only GnRH-a. The women in the escape group had a higher baseline free T concentration than the suppressed group (5.1 vs. 3.3 ng/dl; p = 0.02). The findings revealed that OC therapy following GnRH-a administration effectively maintained ovarian androgen suppression in most women with PCOD. They also indicated that failure to maintain this suppression had a significant association with higher baseline free T concentrations.

Pituitary function is altered during the same cycle in women with polycystic ovary syndrome treated with continuous or cyclic oral contraceptives or a gonadotropin-releasing hormone agonist.

OBJECTIVE: To determine if continuous oral contraceptive (OC) therapy was superior to a cyclic regimen in achieving persistent pituitary suppression of LH in patients with polycystic ovary syndrome (PCOS). DESIGN: Fourteen women (ages 16 to 41 years) with PCOS received one of three treatment groups: continuous OC therapy (30 micrograms ethinyl E2 plus 150 micrograms desogestrel), cyclic OC therapy, or monthly injections of a GnRH agonist (GnRH-a, leuprolide acetate depot 3.75 mg) for 3 months. Basal hormone levels were obtained before initiating therapy, on days 15 to 17 of the 3rd month of treatment (study 1) and again on days 26 to 28 of the 3rd month (study 2). A GnRH stimulation test was also performed during study 1 and study 2. RESULTS: After 3 months of treatment, LH levels were decreased significantly in all groups with less effective suppression observed in the cyclic OC group compared with the continuous OC or GnRH-a groups. A significant rise in LH was found only in the cyclic OC group after 5 to 7 days of placebo treatment (study 1 versus study 2). An increase in T was also observed in the cyclic OC group during study 2, whereas the continuous OC and GnRH-a groups showed continued inhibition of T levels. Although there was no significant difference in LH area under the curve (AUC) measurements after GnRH stimulation in study 1 versus study 2, the LH AUC was significantly greater in both studies in the cyclic OC group compared with the continuous OC or GnRH-a groups. CONCLUSIONS: Increased LH secretion during the week of placebo in the cyclic OC group was associated with a concomitant increase in T. The striking rise in LH secretion after GnRH stimulation in the cyclic OC group may represent increased pituitary sensitivity in patients receiving cyclic OCs regardless of the phase of the treatment cycle, perhaps secondary to increased pituitary stores of LH in these women.

PIP: Clinical researchers recruited 16 women aged 16-41 diagnosed with polycystic ovary syndrome (PCOS) for a study designed to compare their pituitary responsiveness to exogenous gonadotropin releasing hormone (GnRH) stimulation after three months of therapy with either the continuous or cyclic regimen of combined oral contraceptives (OCs). The three treatments included six women on continuous therapy (i.e., every day for 3 months) with an OC containing 30 mcg ethinyl estradiol and 150 mcg desogestrel, six women on cyclic therapy (i.e., 21 days of OC therapy with 7 days of placebo over 3 months) with the same OC formulation, and four women on therapy with a GnRH agonist (GnRH-a), Lupron depot (3.75 mg leuprolide acetate). Luteinizing hormone (LH) levels fell significantly in all groups between baseline and three months treatment (p 0.001). Cyclic OCs exerted a less effective LH suppression than the continuous OC and the GnRH-a, however (88% vs. 99%; p 0.05). Only the cyclic OC group experienced a significant increase in LH after 5-7 days of placebo treatment (126% increase; p 0.008). The percent change in LH levels was significantly different between the cyclic and continuous OC groups (p 0.03) and between the cyclic OC and GnRH-a groups (p 0.01). Similarly, the cyclic OC group had an increase in testosterone levels after 5-7 days of placebo treatment (86% increase), while the other two groups had no change. When both the cyclic and continuous OC groups received their first GnRH stimulation test on days 15-17 of the third 28-day cycle and on days 26-28 (5-7 days of placebo in the OC cyclic group), the LH area under the curve (AUC) measurements were much greater in the cyclic OC group than the continuous OC and the GnRH-a groups (p 0.004). This event suggests increased pituitary sensitivity in patients receiving cyclic OCs regardless of the phase of the treatment cycle; which may be secondary to increased pituitary stores of LH in women with PCOS. These findings support the theory that LH contributes greatly to ovarian testosterone secretion in women with PCOS.

Combination gonadotropin-releasing hormone agonist and oral contraceptive therapy improves treatment of hirsute women with ovarian hyperandrogenism.

OBJECTIVE: To determine if combination GnRH agonist (GnRH-a) and oral contraceptive (OC) therapy was more effective than GnRH-a or OC alone in the treatment of hirsute women with ovarian hyperandrogenism. DESIGN: Thirty-three hirsute women (ages 15 to 39 years) were randomized into three groups: 3.75 mg IM leuprolide acetate (LA) depot every 28 days for 6 months, combination monophasic oral contraceptive for 6 months (OC), or GnRH-a plus OC for 6 months (LA + OC). MAIN OUTCOME MEASURES: Comparative studies of changes in hormonal and hair parameters were performed at baseline, 3, and 6 months after starting therapy. RESULTS: After 6 months, serum T and LH levels were decreased significantly in all groups although reduction was greater in GnRH-a groups than OC alone. The reduction of free T was significantly greater with LA + OC compared with LA or OC alone. This could be a consequence of the significant rise in sex hormone-binding globulin (SHBG) in LA + OC and OC groups compared with LA in which there was no change in SHBG. Reduced facila hair density and decrease in hirsutism score was observed in both GnRH-a groups after 6 months. CONCLUSION: "Add-back" OC therapy used in combination with a GnRH-a increases SHBG and more effectively lowers free T levels in women with ovarian hyperandrogenism. Enhanced suppression of "bioavailable" androgens with combined GnRH-a and OC therapy failed to improve significantly the therapeutic effect of GnRH-a treatment alone on hirsutism.

Sex hormones regulate ABR latency.

In an effort to characterize more completely the influence of sex hormones on auditory brainstem response (ABR) latency, we evaluated the ABRs of normal male and female subjects and women with previously diagnosed endocrinologic syndromes. We describe ABR latency results from the following subjects: five normal males, nine normally cycling females on no hormonal therapy, nine females using oral contraceptive pills, five females with premature ovarian failure (POF) undergoing cyclic estrogen-progesterone replacement therapy, and five hyperandrogenized females with polycystic ovarian disease (PCOD) treated with the gonadotropin-releasing hormone agonist, Lupron depot, to suppress ovarian steroid production. All subjects were between 23 and 40 years of age. Serum levels of estradiol, progesterone, testosterone, prolactic, and gonadotropins (lutienizing hormone and follicle stimulating hormone) were measured to document the hormonal status of each of the subjects at the time of the ABR evaluation. Normal cycling females and females with POF underwent ABR testing during different phases of the same cycle. Male subjects and females using birth control pills were studied four times in the same month at 1-week intervals. Females with PCOD were also studied four times; baseline and then at 2-week intervals after the initiation of Lupron depot therapy. Increased ABR wave V peak latencies were found to be associated with elevated levels of estrogen or testosterone. We have previously reported a lengthening of ABR wave V peak latencies coincident with peak estrogen levels during the female cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance improves in hyperandrogenic women treated with Lupron.

OBJECTIVE: To examine if changes in insulin sensitivity and glucose effectiveness in women with polycystic ovarian disease (PCOD) occurred after ovarian androgen suppression with a GnRH agonist, leuprolide acetate (LA, Lupron; TAP Pharmaceuticals, Deerfield, IL) using the minimal model method. DESIGN: Twelve patients with PCOD were tested in the untreated state (baseline) and after 6 weeks of LA treatment. Subjects were divided into two groups based on the degree of impairment of their baseline insulin sensitivity index (SI; (min-1) (microU/mL-1): mild insulin resistance (SI > 1) or severe insulin resistance (SI < 1). RESULTS: In all patients, serum T was significantly decreased from elevated baseline levels to normal female concentrations after 6 weeks of LA therapy. Insulin sensitivity in PCOD patients with mild insulin resistance significantly improved from baseline after 6 weeks of LA therapy, whereas no change in SI on LA therapy was seen in PCOD women with severe insulin resistance. Glucose utilization independent of increased insulin secretion did not change as a function of LA treatment in either group. CONCLUSION: These findings indicate a significant improvement in SI in mildly insulin-resistant women with PCOD after suppression of ovarian function with LA treatment.

Hormone replacement therapy alters insulin sensitivity in young women with premature ovarian failure.

In this study, we report the effects of cyclic hormone replacement therapy on carbohydrate metabolism in six women with premature ovarian failure. Using tolbutamide-modified iv glucose tolerance tests patients were evaluated during three different intervals of their second treatment cycle: no hormone replacement, estradiol-only (E2-only) replacement, and E2-plus-medroxyprogesterone acetate (MPA) replacement. Insulin sensitivity and glucose effectiveness were derived using insulin and glucose levels obtained from tolbutamide-modified iv glucose tolerance tests and analyzed with the minimal model computer program. The mean insulin sensitivity (x 10(-4)/min/microU.ml) significantly decreased from 4.0 +/- 0.8 during no hormone replacement and 3.8 +/- 0.8 during E2-only replacement to 2.6 +/- 0.5 (x 10(-4)/min/microU/ml) during E2-plus-MPA replacement (P < 0.005). Glucose effectiveness did not change as a function of the phase of hormone replacement therapy. These findings indicate a significant decrease in sensitivity to insulin associated with MPA treatment but no observable change in insulin sensitivity during the E2-only phase of cyclic steroid replacement therapy in young women. Our results support the hypothesis that impairment of insulin-mediated glucose uptake during the luteal phase of the menstrual cycle is due to increased progesterone secretion.

Cyclic steroid replacement alters auditory brainstem responses in young women with premature ovarian failure.

To determine the independent contributions of estradiol and progesterone to the auditory brainstem response (ABR) latency changes associated with the menstrual cycle, we obtained ABRs on young women with premature ovarian failure who were undergoing cyclic hormone replacement therapy (HRT). We evaluated the influence of cyclic HRT on the ABRs of young women in three controlled phases of the same replacement cycles: 1) no steroid replacement, 2) estrogen-only replacement (E2-only), and 3) estrogen-plus-progesterone replacement (E2-plus-P). A significantly lengthening of wave V peak latency and I-V interpeak interval was found during E2-only replacement. Despite equivalent circulating estradiol levels, both wave V peak latencies and wave I-V interpeak intervals significantly decreased during the E2-plus-P replacement phase as compared to the E2-only replacement phase. These findings are compatible with the hypothesis that estradiol potentiates secretion of the inhibitory neurotransmitter gamma-amino-butyric acid (GABA) at auditory nerve synapses, leading to delayed synaptic conduction time. Progesterone is known to blunt E2-potentiated GABA release and may antagonize its prolongation of wave V latency.

Estrogen influences auditory brainstem responses during the normal menstrual cycle.

We evaluated the impact of the menstrual cycle on auditory brainstem response (ABR) latency in nine normally cycling women. Subjects (age 23-40 years) using no hormonal therapy were recruited and underwent ABR testing during four different phases of the same menstrual cycle: early follicular (cycle days 1 to 3); mid-cycle (cycle days 12 to 15); mid-luteal (cycle days 17 to 22), and premenstrual (cycle days 25-27). Cycles were verified by basal body temperature, and serum estrogen (E2), progesterone (P), and gonadotropin levels. A control group of nine women (age 23-40 years) on oral contraceptives (Nordette-28) was also studied four times during a pill cycle. Results show a significant increase in the latency of wave III and wave V peak latencies and in the I-V interpeak interval associated with a high estrogen state at the mid-cycle phase. No statistically significant variations in latency were found in the birth control pill group. These data suggest the existence of brainstem auditory neural pathways that are sensitive to fluctuations in E2 levels during the menstrual cycle.

Does estradiol treatment normalize the hypothalamic-pituitary-adrenal axis in streptozotocin-induced ovariectomized diabetic female rats?

We recently found circulating corticosterone (CS) levels to be significantly lower in diabetic female rats as compared with proestrous control animals. This reduction in CS was correlated with the hypoestrogenic state of the diabetic female. It was the purpose of this study to evaluate basal and corticotropin releasing hormone (CRH)-stimulated CS secretion in ovariectomized (OVX) control (C) and streptozotocin-induced diabetic (D) rats given blank, 5 mcg and 20 mcg estradiol (E2) implants to determine if adrenal CS secretion in the diabetic is normalized by E2 treatment. After 3 weeks of diabetes, pituitary-adrenal function was assessed in rats from each group with a CRH stimulation test. The remaining rats were sacrificed for determination of CS, E2, testosterone and fructosamine in serum. Suppressed CS secretion in OVX female diabetic rats was partially restored with E2 therapy. Basal CS levels were significantly higher in 20 mcg E2 treated C and D rats compared with OVX rats. However, C rats had significantly higher basal CS compared with D rats in similarly E2 treated groups. The CS response to CRH stimulation was not different between OVX female diabetic and control rats. Estrogen enhanced the CS response to CRH stimulation in control animals but not in diabetic animals suggesting altered estrogen action at the pituitary level in diabetic animals.

A short-term comparison of the effects of clomiphene citrate and conjugated equine estrogen in menopausal/castrate women.

An attempt was made to assess the potential role for an antiestrogen in the hormone replacement therapy of menopausal women who have a contraindication to estrogen use. Two groups of menopausal or castrate women were given either conjugated equine estrogen or clomiphene citrate in a cyclic manner for 25 days each month for 3 months. The effects were measured after 3 months and compared with baseline values. Clomiphene lowered FSH slightly, but had no effect on subjective vasomotor symptoms. With respect to bone metabolism, it produced no change in plasma parathyroid hormone level, whereas estrogen lowered it; both compound lowered serum calcium but clomiphene had less effect. The hydroxyproline/creatinine ratio was decreased more by clomiphene than by the estrogen. These findings are consistent with a beneficial effect on bone. Clomiphene had no adverse effects on clotting parameters and showed effects similar to those of conjugated equine estrogens on certain measures of lipid metabolism.

Androgen responses to acutely increased endogenous insulin levels in hyperandrogenic and normal cycling women.

We examined androgen responses in hyperandrogenic (polycystic ovarian disease [PCOD]) and normal women after an acute endogenous insulin elevation. Standard intravenous glucose tolerance tests (IVGTTs), modified to include a tolbutamide injection 20 minutes after IVGTTs, were performed. Polycystic ovarian disease patients were studied in the untreated state, after 6 weeks of ovarian androgen suppression with leuprolide acetate, after a 6-week rest period, and after 6 weeks of antiandrogen therapy with spironolactone. Normal menstruating women were studied during the early follicular, midcycle, and luteal phases of a single cycle. An acute rise in insulin did not alter serum testosterone or androstenedione levels in PCOD or normal women. A significant rise in dehydroepiandrosterone sulfate after modified IVGTTs was found in both hyperandrogenic and normal cycling women. Although these results are not supportive of the theory that insulin acts on the ovary to stimulate androgen production, they may be because of the short time course of insulin elevation that occurs during an IVGTT.

Intravenous glucose tolerance test-derived insulin sensitivity changes during the menstrual cycle.

Using glucose tolerance tests or a glucose clamp some studies report impaired insulin sensitivity during the luteal phase of the menstrual cycle, while others find no change in insulin sensitivity. Tissue sensitivity to insulin and glucose effectiveness can be estimated using the minimal model analysis of an iv glucose tolerance test (IVGTT), but this method has never been applied to evaluate the impact of the menstrual cycle on these parameters. We, therefore, studied eight cycling women using tolbutamide-modified IVGTTs during three different phases of the same menstrual cycle: early follicular, midcycle, and midluteal. Insulin sensitivity (SI) and glucose effectiveness were derived using insulin and glucose levels obtained from tolbutamide-modified IVGTTs and analyzed with the minimal model computer program. The mean SI (x10(-4)/min.microU/mL) decreased in a stepwise fashion from the follicular level of 6.20 +/- 0.91 to a midcycle level of 4.95 +/- 0.73 and was lowest in the luteal phase (3.20 +/- 0.25; P less than 0.007). No change in glucose effectiveness occurred as a function of the menstrual cycle. These findings indicate a significant decrease in insulin sensitivity in the luteal phase of the normal menstrual cycle, but no significant change at midcycle.

The hypothalamic-pituitary axis of streptozotocin-induced diabetic female rats is not normalized by estradiol replacement.

Studies in diabetic rats have found abnormalities at the hypothalamic, pituitary, and/or ovarian level but have not controlled for changes in estrogen levels induced by diabetes. The purpose of this investigation was to study the effect of diabetes on the hypothalamic-pituitary axis in ovariectomized rats treated with estradiol (E2). Ovariectomized 60 day old female rats were assigned to control (C, n = 42), diabetic (D, n = 47) or insulin-treated diabetic (DI, n = 16) groups. Diabetes was induced with an injection of streptozotocin in the D and DI groups. In the C, D, and DI groups, estrogen was replaced by implanting blank, 5 micrograms or 20 micrograms E2 pellets sc. Pituitary LH responsiveness to GnRH was assessed in C and D animals. Anterior hypothalamic and midhypothalamic concentrations of proGnRH and GnRH, pituitary LH and FSH and serum levels of LH, and E2 were measured by RIA. Anterior hypothalamic proGnRH concentrations were decreased in diabetic rats treated with 5 micrograms E2 compared to 5 micrograms E2 control animals (P less than 0.05). Midhypothalamic GnRH concentrations were also reduced in D vs. C animals despite comparable estrogen therapy (P less than 0.004). GnRH-stimulated LH levels were greater in E2-treated diabetic females than in similarly treated control rats (P less than 0.001). D and DI animals were more sensitive than controls to the inhibitory effect of estrogen on basal LH levels. Pituitary LH and FSH content was lower in 20 micrograms E2-replaced animals but was not influenced by the diabetic state. These data demonstrate a diabetes-induced decrease in hypothalamic proGnRH and GnRH concentration which is not corrected with E2 replacement. The hyper-responsiveness of the diabetic rat pituitary to GnRH also suggests a chronic lack of GnRH stimulation from the hypothalamus but a continued ability of the pituitary to respond to GnRH.

Sequential Gn-RH superagonist and medroxyprogesterone acetate treatment of uterine leiomyomata.

A group of 48 women with symptomatic leiomyomata were treated during 6 months with the short-acting Gn-RH superagonist analog buserelin. The first (group C) was followed up for an additional six months of no medication. The second (group M) was treated for 6 additional months with medroxyprogesterone acetate (MPA) at doses decreasing from 200 to 25 mg/day. Buserelin therapy significantly decreased uterine size (P less than 0.001) in all patients, the average final volume being 48.5% of the original (from 262 +/- 147 ml to 127 +/- 85.4 ml). In group C there was a significant (P less than 0.001) re-growth during the post-treatment observation period (from 120 +/- 81.0 ml to 198 +/- 77.2 ml); a significant (P less than 0.01) re-growth was also observed in group M during MPA medication (from 132 +/- 77.2 ml to 170 +/- 96.0 ml). The agonist had also a marked effect on fibroids: on average they decreased from 75.1 +/- 74.3 ml to 24.7 +/- 23.3 ml (P less than 0.025). In group C during the post-buserelin period of observation without treatment, there was a significant re-growth from 23.7 +/- 21.6 ml to 47.7 +/- 27.5 ml (P less than 0.001), whereas in group M treatment with MPA prevented any significant re-growth (from 25.6 +/- 24.8 to 30.6 +/- 32.9 ml; P greater than 0.3).