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Biomedical subjects

H S Jacobs

Publications and source records attributed to H S Jacobs.

At least 109 records · Page 6Linked to original sources
PubMed1992

11 beta-hydroxyandrostenedione in plasma, follicular fluid, and granulosa cells of women with normal and polycystic ovaries.

OBJECTIVE: To investigate the role of 11 beta-hydroxylase/11 beta-hydroxyandrostenedione (11-OHA) in the ovarian metabolism of androgens in women with polycystic ovaries (PCO) and its associated syndrome (PCOS). DESIGN: Prospective observational study examining the plasma and follicular fluid (FF) concentrations of 11-OHA, testosterone (T), androstenedione (A), and cortisol from women with PCOS and normal women in spontaneous and stimulated cycles. SETTING: The study was carried out in an infertility department and an endocrine research laboratory of a university hospital. PATIENTS: Five groups of women were studied. Blood was taken from 53 women with PCOS and 13 normal controls. Follicular fluid and blood was obtained from 51 women with stimulated cycles undergoing in vitro fertilization embryo-transfer (IVF-ET), 27 of whom had PCO and 24 had normal ovaries. Follicular fluid alone was also taken from 13 women with normal ovaries undergoing laparoscopies. INTERVENTIONS: Clear FF was obtained for analysis during oocyte collection. Granulosa cells (GCs) were obtained from seven women with PCO undergoing IVF-ET and were incubated with radiolabeled substrates. RESULTS: Circulating concentrations of T and 11-OHA were higher in women with PCOS compared with women with normal ovaries. In women with PCO receiving exogenous gonadotropin, only 11-OHA concentrations were higher. Concentrations of all steroids measured were higher in FF than plasma, with plasma 11-OHA concentrations 4 to 12 times higher in FF. Significantly lower concentrations of 11-OHA were found in the FF of women with PCO compared with women with normal ovaries. There was no evidence of 11 beta-hydroxylation of A by GCs. CONCLUSIONS: Although the raised plasma concentrations of 11-OHA may reflect hyperandrogenism in PCOS and lower 11-OHA concentrations in FF in women with PCO suggest abnormal androgen metabolism, neither can be regarded as a marker for this syndrome.

Androstenedione↗
PubMed1992

Creutzfeldt-Jakob disease in recipients of human growth hormone in the United Kingdom: a clinical and radiographic study.

In the past 3 years there have been five further cases, in addition to one case reported in 1985, of Creutzfeldt-Jakob disease in recipients of human growth hormone in the United Kingdom. The clinical findings of two of these cases are described, demonstrating a typical presentation with a predominantly cerebellar syndrome at onset which is not commonly a presenting feature of sporadic Creutzfeldt-Jakob disease. In one case a 99mTc hexamethylpropylenamine single photon emission tomographic scan showed marked impairment of tracer uptake in the basal ganglia and cerebral cortex at a time when the clinical picture was predominantly cerebellar. This technique may be useful in early diagnosis. In the other case post mortem examination of the brain showed prominent amyloid deposition in the cerebellum, which has not been described previously in pituitary-hormone related Creutzfeldt-Jakob disease. The previously published cases of growth hormone-related Creutzfeldt-Jakob disease are reviewed and reasons for the particular clinical pattern seen are discussed.

Adult↗
PubMed1992

Cotreatment with growth hormone for induction of spermatogenesis in patients with hypogonadotropic hypogonadism.

OBJECTIVE: To induce spermatogenesis by cotreatment with growth hormone (GH) and gonadotropin therapy in patients with hypogonadotropic hypogonadism who had failed to respond adequately to conventional treatment. DESIGN: Cotreatment with GH (4 IU) and human menopausal gonadotropin, 150 IU of follicle-stimulating hormone and 150 IU of luteinizing hormone (LH), three times a week, and human chorionic gonadotropin, 2,500 IU, two times a week for 24 weeks after unsuccessful treatment for 12 weeks with either pulsatile LH-releasing hormone or gonadotropins. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Seven patients, four of whom had failed to respond adequately to the conventional treatment. MAIN OUTCOME MEASURES: Serum testosterone (T), estradiol, and sperm production, testicular and semen volume, and serum insulin-like growth factor-I and inhibin concentrations. RESULTS: Of the four patients who received cotreatment with GH, three increased T secretion (greater than 11 nmol/L) within a relatively short period of time, two produced adequate amount of sperm (13 and 12 x 10(6)/mL), and one of them impregnated his wife. One patient did not respond. CONCLUSION: The results offer a new approach to the problem of induction of spermatogenesis in patients who respond poorly to conventional treatment because cotreatment with GH enhanced T secretion and sperm production in a relatively short period of time.

Adult↗
PubMed1991

The determination of 11 beta-hydroxyandrostenedione in human follicular fluid and plasma.

The development of a chromatographic/immunoassay method is presented for the measurement of 11 beta-hydroxyandrostenedione (11 beta-OH-A4) in ovarian follicular fluid (FFL) and plasma from women undergoing embryo transfer for in vitro fertilization. This method incorporates high-performance liquid chromatography (HPLC) and permits the simultaneous measurement of other steroids from a single sample in order to assess the intraovarian environment. Authenticity of 11 beta-OH-A4 in follicular fluid was confirmed using selected ion monitoring (SIM) gas chromatography/mass spectrometry (GC/MS). Our results demonstrate a mean concentration of 18.6 nmol/l in follicular fluid compared with 3.2 nmol/l in plasma. The origin of 11 beta-OH-A4 in follicular fluid requires further investigation but these findings supports the hypothesis of ovarian 11 beta-hydroxylase activity on C19 steroids.

Adrenal Glands↗
PubMed1991

CV 205-502--effectiveness, tolerability, and safety over 24-month study.

Twenty hyperprolactinemic women (median prolactin [PRL] 2,989 mU/L, range 1,149 to 11,910 mU/L), previously unsuccessfully treated with bromocriptine, were treated in a prospective study, for 3 to 24 months with the new, nonergot, long-acting, dopamine agonist, CV 205-502. Treatment resulted in normalization of PRL in 14 patients, in one daily dose of 0.075 to 0.150 mg of the drug. Three patients were treated in doses above 0.150 mg up to 0.300 mg, but PRL was not normalized during the study. Menstrual function was restored in 15 of 18 amenorrheic patients. Galactorrhea, present in 7 patients, disappeared in 5. Four patients became pregnant and gave birth to healthy children. In conclusion, we found CV 205-502 effective in one daily dose, with good tolerability; it is safe and provides a valuable alternative to the dopamine agonist drugs in use today.

Adult↗
PubMed1991

Polycystic ovarian syndrome: safety and effectiveness of stepwise and low-dose administration of purified follicle-stimulating hormone.

OBJECTIVE: An attempt to induce ovulation with a single dominant follicle in polycystic ovarian syndrome (PCOS) patients. DESIGN: Comparing ultrasound and estradiol (E2) measurements during treatment with a low-dose protocol (using purified follicle-stimulating hormone, starting with 75 IU/d and increasing every 7 days by 37.5 IU/d) with those obtained following treatment with a conventional protocol using the same drug. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS PARTICIPANTS: Eight PCOS patients of whom six had failed to respond adequately to the conventional protocol. MAIN OUTCOME MEASURE: Rate of cancellation of cycles, number of leading follicles, and serum E2 concentration at the time of ovulation. RESULTS: Treatment with the low-dose protocol resulted in a significant reduction in the number of leading follicles (P less than 0.04), serum E2 concentrations (P less than 0.0002), and a higher rate of ovulation. As a result, five patients conceived compared with none in the conventional protocol. CONCLUSION: Using the low-dose protocol permitted induction of ovulation safely and successfully in a selected group of PCOS patients who were previously difficult to treat with the conventional ovulation induction protocol.

Adult↗
PubMed1991

Is it possible to run a successful ovulation induction program based solely on ultrasound monitoring? The importance of endometrial measurements.

OBJECTIVE: To attempt the monitoring of ovulation induction solely with ultrasound (US). DESIGN: Using serial US measurements to monitor ovulation induction using human menopausal gonadotropin and human chorionic gonadotropin (hCG), in comparison with estradiol (E2) concentrations that became available at the end of each cycle. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients. MAIN OUTCOME MEASURE: Follicular growth, uterine measurements, endometrial thickness, and serum E2 concentrations. RESULTS: Follicular growth, uterine measurements, and endometrial thickness correlated strongly with E2 concentrations (P less than 0.0001). The endometrium on the day of hCG administration was significantly thicker (P less than 0.01) in the conception (n = 27) compared with the nonconception cycles (n = 87), whereas no significant difference were observed in serum E2 concentrations. No pregnancy was observed when hCG had been administered when the endometrial thickness was less than or equal to 7 mm. Midluteal endometrial thickness of greater than or equal to 11 mm was found to be a good prognostic factor for detecting early pregnancy (P less than 0.008). CONCLUSIONS: Serial US examinations used alone have proven to be safe and highly efficient. It also has a unique ability to detect pregnancy in the midluteal phase.

Adult↗
PubMed1991

Results of ovulation induction using human menopausal gonadotropin or purified follicle-stimulating hormone in hypogonadotropic hypogonadism patients.

OBJECTIVE: To compare ovarian performance and hormonal levels, after ovulation induction, in patients with isolated hypogonadotropic hypogonadism, using two different gonadotropin drugs. DESIGN: Patients were treated during consecutive cycles, using the same stimulation protocol, with human menopausal gonadotropin (hMG) in the first treatment cycle and purified follicle-stimulating hormone (FSH) in the second one. SETTING: Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS: Nine patients with isolated hypogonadotropic hypogonadism. MAIN OUTCOME MEASURE: Duration of stimulation, number of leading follicles, serum estradiol (E2) concentration and endometrial thickness at the time of human chorionic gonadotropin administration, and the occurrence of ovulation. RESULTS: Compared with hMG, treatment with purified FSH required significantly more ampules of drug (P less than 0.04) but resulted in a significant reduction in the number of leading follicles (P less than 0.05), serum E2 concentrations (P less than 0.002), endometrial thickness (P less than 0.02) and the occurrence of ovulation (P less than 0.05). CONCLUSION: This study in isolated hypogonadotropic hypogonadism patients is consistent with the two-cell two-gonadotropin hypothesis, that both gonadotropins are required to accommodate their synergistic action for appropriate steroidogenesis. In treating this group of patients, the superior efficacy of hMG compared with purified FSH preparation is beyond question.

Adult↗
PubMed1991

Cotreatment with growth hormone, after pituitary suppression, for ovarian stimulation in in vitro fertilization: a randomized, double-blind, placebo-control trial.

OBJECTIVE: To explore the effect of cotreatment with growth hormone (GH) for ovarian stimulation after pituitary suppression. DESIGN: A randomized, double-blind, placebo-controlled study. SETTING: Specialist Reproductive Endocrine and In Vitro Fertilization (IVF) Unit. PATIENTS, PARTICIPANTS: Twenty-five IVF patients who had responded suboptimally in a previous treatment cycle. A subgroup of 18 patients were found to have ultrasound (US) findings of polycystic ovaries (PCO). MAIN OUTCOME MEASURE: The amount of gonadotropin used, development of follicles greater than or equal to 14 mm, number of oocytes collected, fertilized, cleaved and replaced, serum and follicular fluid (FF) insulin-like growth factor I (IGF-I) concentrations. RESULTS: Cotreatment with GH was associated with a significant reduction in gonadotropins requirement (P less than 0.05). In patients with US-diagnosed PCO more follicles developed (P less than 0.05), more oocytes were collected (P less than 0.03), fertilized (P less than 0.004), and cleaved (P less than 0.02). A significantly higher FF IGF-I concentrations were found in patients receiving cotreatment with GH compared with those who received placebo (P less than 0.04). CONCLUSION: We believe that there may be a place for GH treatment in selected IVF cycles after pituitary suppression but what the role of IGF-I should further be investigated.

Adult↗
PubMed1991

Co-treatment with growth hormone of sub-optimal responders in IVF-ET.

Several growth factors augment the ovarian response to gonadotrophins and growth hormone is known to regulate the production of insulin-like growth factor-1. With this in mind, 20 women who had previously responded sub-optimally to standard ovarian stimulation regimens for in-vitro fertilization and embryo transfer (IVF-ET) were recruited into a randomized trial to study the effect of co-treatment with growth hormone (Norditropin, Novo Nordisk Gentofte A/S). Intramuscular injections of growth hormone (24 IU) or placebo were given on alternate days concurrently with the same daily dosage of gonadotrophin as administered in the patient's pretreatment cycle. Overall, there was no improvement in the ovarian response to the growth hormone-augmented regimen of stimulation although there was a tendency for the development of more follicles (P = 0.06). When the results from the patients with ultrasound-diagnosed polycystic ovaries were analysed separately, however, more follicles developed (P = 0.04), more oocytes were collected (P = 0.03) and there was a trend towards higher urinary oestrogen production following growth hormone therapy. There was no improvement in the ovarian response in patients with normal ovaries. The treatment was not associated with any adverse effects. We conclude, therefore, that in a subgroup of patients who respond sub-optimally to standard ovarian stimulation regimens for IVF-ET and who have ultrasound-diagnosed polycystic ovaries, systemic growth hormone is an effective adjunctive therapy.

Clomiphene↗
PubMed1991

The hormonal profile of women with acne and polycystic ovaries.

Most women with acne are found to have polycystic ovaries on high resolution pelvic ultrasonography, but most of these women do not manifest the other classical clinical characteristics of the polycystic ovary syndrome. We have compared the endocrinological profile of women with acne who were found to have polycystic ovaries with that of women with polycystic ovaries who presented to an endocrine clinic with hirsutes or non-dermatological manifestations of the polycystic-ovary syndrome. The group of women with acne had normal serum hormonal concentrations. Unlike other women with polycystic ovaries, they did not have significantly elevated serum concentrations of luteinizing hormone or testosterone. By clinical and endocrinological criteria, patients with acne who have polycystic ovaries appear to be a distinct sub-population of women with polycystic ovaries.

Acne Vulgaris↗
PubMed1991

The pathogenesis of the ovarian hyperstimulation syndrome (OHS): a possible role for ovarian renin.

Two patients with severe ovarian hyperstimulation syndrome are described. Increased plasma concentrations of immunoradiometrically determined total renin are shown, together with greatly increased plasma levels of active renin and aldosterone. These very high values for total renin, renin activity and aldosterone were not suppressed when extracellular compartments were greatly expanded; the values subsequently declined to normal levels, despite the use of diuretics. This suggested that the renin was of non-renal origin since its production was apparently unaffected by influences which control juxtaglomerular secretion. The high concentrations of the renin-angiotensin-aldosterone system suggest that it contributes to the genesis of the ovarian hyperstimulation syndrome.

Adult↗
PubMed1991

Serum and follicular fluid insulin like growth factors I and II during growth hormone co-treatment for in-vitro fertilization and embryo transfer.

OBJECTIVE: We wished to assess the changes in serum IGF-I and IGF-II concentrations during gonadotrophin treatment alone or with additional GH treatment and to compare follicular fluid IGF-I and IGF-II concentrations in the two treatment groups. DESIGN: We performed an open study of co-treatment with GH and subsequently a randomized double blind comparison of addition of placebo or GH to clomiphene citrate and gonadotrophins. PATIENTS: We studied previously poor responders to superovulation regimens for in-vitro fertilization and embryo transfer, six women in an open study, four of whom had ultrasound diagnosed polycystic ovaries, and 17 women in a double blind study, 12 of whom had polycystic ovaries. MEASUREMENTS: We measured serum IGF-I and IGF-II concentrations throughout treatment cycles. Follicular fluid concentrations were measured at the time of oocyte recovery. RESULTS: Neither serum IGF-I nor IGF-II concentrations were altered by gonadotrophin treatment alone. However, co-treatment with GH led to a significant rise in serum IGF-I concentrations in women with ultrasound diagnosed polycystic ovaries. Concentrations of IGF-I and IGF-II in follicular fluid were lower than in serum, although follicular fluid IGF-I concentrations were higher in women receiving GH than in those receiving placebo. CONCLUSIONS: Poor responders to superovulation regimens may have an abnormality of growth factor response. GH co-treatment leads to an increase in circulating IGF-I concentrations in women with polycystic ovaries but our results do not support the hypothesis that GH stimulates IGF-I production in the human ovary.

Adult↗
PubMed1991

Combined growth hormone and gonadotropin treatment for ovulation induction in patients with non-responsive ovaries.

Four anovulatory patients who did not respond to large doses of hMG over 18-33 days were co-treated in subsequent cycles with human growth hormone. Treatment with growth hormone markedly raised serum insulin-like growth factor concentrations. Two patients had a dramatic ovarian response within 7 days of co-treatment; two menopausal patients did not respond. This combined therapy may be of practical value for ovulation induction in non-menopausal patients with non-responsive ovaries.

Addison Disease↗
PubMed1990

Hypersecretion of luteinising hormone, infertility, and miscarriage.

The relation between prepregnancy follicular-phase serum luteinising hormone (LH) concentrations and outcome of pregnancy was investigated prospectively in 193 women with regular spontaneous menstrual cycles. The group included 26 nulliparous and 167 multiparous women with various obstetric histories. Of the 147 women with LH concentrations of less than 10 IU/l (normal LH group) 130 (88%) conceived, whereas only 31 (67%) of the 46 women with LH values of 10 IU/l or more (high LH group) did so. In the high LH group, 20 (65%) of the pregnancies ended in miscarriage, whereas only 15 (12%) of pregnancies in the normal LH group did so. The adverse effect of a high prepregnancy LH concentration on fertility and outcome of pregnancy was seen in primigravidae, women with previously successful pregnancies, and women with a history of recurrent miscarriage. These data indicate an important role for hypersecretion of LH before conception in miscarriage. This finding offers the possibility of a simple predictive test for women before pregnancy, and could also be used to identify patients with an endocrine abnormality that can be remedied.

Abortion, Habitual↗
PubMed1990

Bone mineral loss in young women with amenorrhoea.

OBJECTIVE: To examine the impact of amenorrhoea on bone mineral density in women of reproductive age. DESIGN: Cross sectional study of 200 amenorrhoeic women compared with normally menstruating controls. SETTING: Teaching hospital outpatient clinic specialising in reproductive medicine. SUBJECTS: 200 Women aged 16-40 with a past or current history of amenorrhoea from various causes and of a median duration of three years, and a control group of 57 age matched normal volunteers with no history of menstrual disorder. MAIN OUTCOME MEASURE: Bone mineral density in the lumbar spine (L1-L4) as measured by dual energy x ray absorptiometry. RESULTS: The amenorrhoeic group showed a mean reduction in bone mineral density of 15% (95% confidence interval 12% to 18%) as compared with controls (mean bone mineral density 0.89 (SD 0.12) g/cm2 v 1.05 (0.09) g/cm2 in controls). Bone loss was related to the duration of amenorrhoea and the severity of oestrogen deficiency rather than to the underlying diagnosis. Patients with a history of fracture had significantly lower bone density than those without a history of fracture. Ten patients had suffered an apparently atraumatic fracture. CONCLUSIONS: Amenorrhoea in young women should be investigated and treated to prevent bone mineral loss. Menopausal women with a past history of amenorrhoea should be considered to be at high risk of osteoporosis.

Absorptiometry, Photon↗