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Biomedical subjects

H G Burger

Publications and source records attributed to H G Burger.

At least 91 records · Page 5Linked to original sources

Age and follicular phase estradiol are better predictors of pregnancy outcome than luteinizing hormone in menotropin ovulation induction for anovulatory polycystic ovarian syndrome.

OBJECTIVE: To examine the relationship of baseline and preovulatory serum E2, P, and LH levels and age with pregnancy outcome in polycystic ovarian syndrome (PCOS) patients undergoing hMG ovulation induction. DESIGN: Retrospective analysis of all available data over 2 years. SETTING: Tertiary referral ovulation induction clinic. SUBJECTS: Forty-four anovulatory PCOS patients with 25 ovulatory nonconception and 50 conception cycles after hMG ovulation induction. MAIN OUTCOME MEASURES: Ovulation (midluteal serum P > 25 nmol/L [7.86 ng/mL]); pregnancy (serum beta-hCG > 30 mIU/mL 16 days after ovulating injection); pregnancy outcome: pregnancy termination < 20 weeks' or > or = 20 weeks' amenorrhea. RESULTS: Of the endocrine parameters considered, none was significantly different in nonconceptive and conceptive ovulatory cycles. Miscarriage was associated with low basal serum E2: median value for pregnancies ending < 20 weeks, 105 pmol/L (28.6 pg/mL) and for > or = 20 weeks 150 pmol/L (40.9 pg/mL). It was also significantly associated with age. For patients > 29.5 years of age, (29.5 years, population mean age) a baseline E2 < or = 140 pmol/L (38.2 pg/mL) had sensitivity 92%, specificity 54%, positive predictive value 65%, and negative predictive value 87% for the prediction of miscarriage. The nature of the previous cycle, the day of the cycle on which therapy commenced, and a past history of miscarriage were not related either to pregnancy outcome or to basal serum E2.

Abortion, Spontaneous↗

Evidence for a negative feedback role of inhibin in follicle stimulating hormone regulation in women.

The pituitary--ovarian axis describes a regulatory system in which pituitary gonadotrophins stimulate ovarian folliculogenesis and the production of both steroid and protein hormones, which in turn exercise feedback control on the pituitary and hypothalamus. The availability of a radioimmunoassay for serum inhibin has allowed exploration of inhibin's role in the regulation of follicle stimulating hormone (FSH). This gonadotrophin stimulates ovarian inhibin secretion within the physiological dose range, both after exogenous administration and during endogenous rises, as are seen during puberty and the mid-cycle FSH surge. No direct evidence of FSH suppression by inhibin administered to human subjects has been obtained. During periods of endogenously raised inhibin levels, however, FSH is suppressed, as seen during the luteal phase of the menstrual cycle (luteinizing hormone drives inhibin production at that time), during pregnancy and in patients with inhibin-secreting granulosa cell tumors of the ovary. In contrast, decreased inhibin levels in the presence of intact hypothalamo-pituitary function result in increased FSH concentrations--as in early childhood, during the luteal-follicular transition and during reproductive ageing. After the menopause inhibin levels are normally undetectable, with FSH being markedly elevated. These observations are compatible with a role for endogenous inhibin in the regulation of FSH, though the contribution of oestradiol is in most instances impossible to dissect out separately.

Feedback↗

Clinical and pathophysiological aspects of inhibin.

Inhibin is a peptide hormone normally produced by the ovary. We have previously reported that serum inhibin concentrations are elevated in patients with granulosa cell tumours of the ovary. The aim of this study was to measure serum inhibin in a prospective, consecutive series of 200 patients admitted for suspected ovarian cancer. The serum inhibin radioimmunoassay had a sensitivity of 77 mu/l. The median effective dose was 640 mu/l, while within- and between-assay coefficients of variation in the region of maximal assay precision were 4.3% and 4.3%, respectively. The average effective doses (10 and 90%) in 35 consecutive assays were 211 and 1908 mu/l, respectively. We designated a serum inhibin concentration of > or = 130 mu/l as pathological in castrate or functionally agonadal women. Serum inhibin concentrations were elevated in 12 of 13 post-menopausal patients with mucinous cystadenocarcinoma of the ovary. By contrast, elevated serum inhibin values were found in only nine of 65 women with non-mucinous epithelial ovarian cancers. All patients showed a fall in serum inhibin levels to below 130 mu/l by 1 week after surgery. In post-menopausal women (n = 54) with proven ovarian cancer, serum inhibin concentrations correlated negatively with serum FSH and the clinical stage of their disease (P < 0.05). By contrast, serum inhibin correlated positively with serum oestradiol and progesterone (P < 0.001) but there was no correlation between serum inhibition and serum CA-125 values. We conclude that serum inhibin concentrations are typically elevated in patients proven to have mucinous cystadenocarcinoma of the ovary.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗

Follicle-stimulating hormone induces dose-dependant stimulation of immunoreactive inhibin secretion during the follicular phase of the human menstrual cycle.

To determine whether FSH is a physiological regulator of the serum immunoreactive inhibin (INH) concentration during the follicular phase of the normal menstrual cycle, purified FSH (Metrodin) was administered in doses of 100 IU (n = 6), 150 IU (n = 5), and 200 IU (n = 5) to normal, regularly cycling volunteers between days 3-7 of the menstrual cycle. A control group (n = 5) received normal saline. There was a linear dose-related increase in serum INH (and in serum FSH) in response to the three doses of FSH, with 200 IU leading to a 107% increase in INH and a 68% increase in FSH. Serum estradiol rose in response to the two higher doses of FSH. There was a significant correlation between the actual increases in INH and estradiol (r = 0.53; P < 0.01). It was concluded that FSH stimulates INH in the follicular phase of the normal menstrual cycle, consistent with a physiological role for FSH in the regulation of granulosa cell production of inhibin.

Adult↗

Clinical review 46: Clinical utility of inhibin measurements.

New and specific assays, probably based on two-site assay technology, for various forms of circulating gonadal peptides are likely to be available within the next few years and these in turn should open up a range of potential clinical applications, particularly in andrology, management of ovulatory disorders, and especially ovarian and perhaps other malignancies. Current inhibin assays are already proving to be of great value in ovarian cancer management. The recent demonstration that inhibin subunits and dimeric activin are present in the human adrenal also raises the possibility that measurement of inhibin and activin may ultimately be applicable to the study of adrenal disorders.

Activins↗

Does gonadotropin suppression result in follicular development in premature ovarian failure?

It was hypothesized that premature ovarian failure is a self-perpetuating problem and that suppression of the endogenously raised gonadotropin levels may allow synchronization of follicular growth, so that when the suppression is removed, follicular development may be stimulated by the rapid rise in follicle stimulating hormone (FSH) levels. Microgynon (ethinylestradiol, 30 micrograms and levonorgestrel, 150 micrograms) was administered to eight women with premature ovarian failure for 12 weeks. Serum samples were collected weekly for radioimmunoassay of FSH, luteinizing hormone (LH), estradiol, progesterone and inhibin. On stopping Microgynon, ovarian ultrasonography was carried out, in addition to blood sampling, to monitor any follicular growth. Both FSH and LH levels declined to the normal follicular-phase range after 5 weeks of Microgynon treatment (mean +/- SD: FSH, 6.5 +/- 1.2 IU/l; LH, 8.9 +/- 1.6 IU/l). Both hormone levels rose rapidly after stopping treatment and were above the normal follicular-phase range by the 1st week. FSH reached pretreatment levels by 3 weeks, but LH did not reach the previously high levels until 7 weeks after stopping Microgynon administration. Estradiol and immunoreactive inhibin levels in serum were undetectable throughout the study. No follicular growth was seen on ultrasound scanning. Therefore, gonadotropin suppression in premature ovarian failure does not result in a resumption of follicular activity.

Adult↗

Body weight, body mass index, and age: predictors of menotropin dose and cycle outcome in polycystic ovarian syndrome?

Whereas the dose of hMG is significantly correlated with both BMI and BW, commencing the more obese patient on higher hMG doses is not justified in view of the cancellation of cycles from over-responsiveness in the more obese patients started on higher hMG dosage regimens. If the more obese patient is slow to respond, however, a greater degree of clinical freedom may be exercised to increase the dose. The ultimate outcome of the cycle is not related to BMI, BW, or the dose of hMG used.

Aging↗

Inhibin as a marker for granulosa cell tumor.

In order to determine whether serum-immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with granulosa cell tumor. Six series were tested in retrospect. From these, three came from patients who had been treated with an abdominal hysterectomy and bilateral salpingo-oophorectomy. In the 2 patients with residual or recurrent disease, inhibin was elevated, 4 and 20 months respectively before clinical manifestations of recurrence became evident; it reflected the effects of secondary therapy. Inhibin remained undetectable in one patient who was free of disease during 11 years of follow-up. Inhibin concentrations were also inappropriately increased in 2 of 3 women with amenorrhea and infertility resulting from small granulosa cell tumors. After removal, inhibin concentrations became normal and fertility resumed. Fertility also returned in the third patient. There was a significant negative correlation between the serum inhibin and FSH concentrations, consistent with autonomous production of inhibin by granulosa cell tumors. It is concluded that granulosa cell tumors have the capacity to produce inhibin. In retrospect, inhibin proved to be a marker for both primary and also recurrent and residual disease.

Adult↗

Vaginal progesterone administration in physiological doses normalizes raised luteinizing hormone levels in patients with polycystic ovarian syndrome.

A raised luteinizing hormone (LH) level is a typical finding in the polycystic ovarian syndrome (PCOS). This inappropriate elevation of LH is thought to interfere with normal follicular development and ovulation. The resulting chronic anovulation is associated with the absence of the luteal phase increase in secretion of progesterone and inhibin. Progesterone can exert both a positive and negative feedback action on LH secretion, but inhibition is thought to occur following prolonged exposure to progesterone. Therefore, the aim of this study was to see if exogenously administered progesterone in physiological doses would normalize circulating LH concentrations in patients with PCOS. Vaginal progesterone was administered twice daily in a dose of 100 mg, at 12 h intervals, to ten women with PCOS. Serum samples were taken on alternate days for radioimmunoassay of follicle stimulating hormone (FSH), LH, estradiol, progesterone and inhibin. To determine the effect of progesterone on LH secretory dynamics in PCOS, LH pulse studies were carried out prior to treatment, and on day 10 of progesterone administration in four of the ten subjects. Mean serum progesterone concentrations reached 51 nmol/l by 4 days after exogenous progesterone treatment, and remained in the mid-luteal phase range, as established in 12 normal cycles, during the use of the vaginal suppository. The mean serum LH concentration had fallen significantly (p < or = 0.01) after 8 days of treatment, and continued to fall progressively until the end of progesterone administration. Serum LH concentrations had fallen into the normal follicular phase range by 14 days (mean 5.5, range 3.4-10.9 IU/l; normal follicular phase range 1.8-10.0 IU/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Estradiol↗

Update on endocrinology.

Endocrinology covers diverse groups of organs and diseases. In this article, advances in the investigation of thyroid dysfunction, the management of Paget's disease of bone and the investigation and management of polycystic ovary syndrome are discussed.

Calcitonin↗

Young's syndrome (obstructive azoospermia and chronic sinobronchial infection): a quantitative study of axonemal ultrastructure and function.

The ultrastructure and function of nasal cilia and sperm tails were examined in 23 men with Young's syndrome and compared with data previously collected from 10 normal subjects. Quantitative electron microscopic assessment showed that sperm tails from patients with Young's syndrome contained significantly fewer central pair microtubules, radial spokes, and inner dynein arms, and their cilia contained less inner dynein arms than normal subjects. The Young's syndrome patients had normal in vitro ciliary beat frequency (11.4 +/- 0.9 Hz), and 12 of the 23 had normal nasal mucociliary clearance (15.0 +/- 5.0 minutes). However, the remaining 11 had markedly abnormal nasal mucociliary clearance in vivo. In these patients, the deficiency of ciliary inner dynein arms did not appear to affect ciliary function in vitro but may under mucus loading lead to abnormal in vivo ciliary function. The consistent abnormalities shown in cilia and sperm tails, though apparently minor, constitute a common factor in both the reproductive and respiratory tracts which may, in combination with abnormalities in the in vivo environment, lead to the features of Young's syndrome.

Adult↗

Elevation of follicular phase inhibin and luteinizing hormone levels in mothers of dizygotic twins suggests nonovarian control of human multiple ovulation.

OBJECTIVE: To determine whether multiple ovulation in mothers of spontaneous dizygotic (DZ) twins is because of higher hypothalamic stimulation or is in response to lower serum levels of ovarian inhibin. DESIGN: Serum hormone levels were measured at five times throughout the cycle in a sample of eight mothers of DZ twins and paired controls. On day 12, ovarian ultrasonography was performed. SETTING: Blood samples were collected in participants' homes except on day 12 when they were collected at the ultrasonography clinic. PATIENTS, PARTICIPANTS: Human volunteers who had at least one set of spontaneous DZ twins were paired with controls matched for age and parity. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum inhibin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on approximate cycle days 1,2,8,12, and 21. RESULTS: Serum inhibin levels were elevated throughout the cycle (significantly on day 1) in mothers of DZ twins. Also elevated were early follicular FSH levels, LH levels throughout the follicular phase (significantly on days 1,2, and 8), and early to midfollicular E2 (significantly on day 8) in DZ mothers, indicative overall of greater follicular activity. CONCLUSION: It is concluded (1) that the primary cause of multiple ovulation in humans is not a decrease in inhibin secretion from the ovary; (2) the increased secretion of FSH and LH may be caused by elevated secretion of, or sensitivity to gonadotropin-releasing hormone; and (3) the elevated inhibin and E2 levels are a response to increased gonadotropin release.

Female↗

Circulating levels of inhibin in pregnant women at term: simultaneous disappearance with oestradiol and progesterone after delivery.

Circulating levels of immunoreactive inhibin (ir-inhibin) and its disappearance after delivery of the placenta were determined in seven pregnant women at term. Serum oestradiol (E2) and progesterone (P4) levels were measured simultaneously and served as comparisons. Fetal contributions of ir-inhibin were assessed by determining concentrations in the umbilical artery (UA) and vein (UV). Relative changes in circulating levels of ir-inhibin, E2, and P4 were compared to levels found in nonpregnant women during the early follicular phase (EFP) and mid-luteal phase (MLP) of the normal menstrual cycle. In pregnant women, ir-inhibin levels at delivery were 15- and 3-fold higher than EFP and MLP values respectively. The disappearance of all three hormones after removal of the placenta followed a bi-exponential curve with an initial, rapid component and a second, slower component. There was a highly significant positive correlation between the disappearance curves of all three placental hormones (r = 0.97, P less than 0.0001). Concentrations of ir-inhibin in the cord blood were about half that in maternal serum and without significant difference between levels in UA and UV.

Adolescent↗

Ovarian sensitization to gonadotrophins by human growth hormone. Persistence of the effect beyond the treated cycle.

OBJECTIVE: To document the persistence of a sensitizing effect of human growth hormone on the ovarian responsiveness to human menopausal gonadotrophin in anovulatory patients resistant to standard gonadotrophin doses. DESIGN: We performed an open study of three patients given 4, 12 or 24 IU recombinant growth hormone on alternate days for 5-7 doses, concomitantly with gonadotrophin, and assessed gonadotrophin dose requirements before, during and after the cycle of growth hormone therapy. PATIENTS: We studied two with isolated gonadotrophin deficiency and primary amenorrhoea and one with a pituitary tumour and hyperprolactinaemia which normalized with bromocriptine but in whom there was persisting secondary amenorrhoea. MEASUREMENTS: We measured body mass index, FSH, LH, prolactin, growth hormone, insulin-like growth factor I (IGF-I), oestradiol and inhibin at baseline and growth hormone, IGF-I, oestradiol and inhibin during treatment. In addition we noted the numbers of ampoules (75 IU) and the last pre-hCG dose of gonadotrophin used before, during and after growth hormone therapy. RESULTS: Baseline growth hormone levels were low but IGF-I levels were normal. IGF-I increased by 20% in the subject given 4 IU growth hormone, and by 50-100% in the other two. Pretreatment daily gonadotrophin dosage of 8-11 ampoules pre-hCG was reduced to 3-6 ampoules during growth hormone and 3-4 post growth hormone. This effect persisted for 4 cycles over 7 months in one subject. CONCLUSION: Growth hormone causes persisting ovarian sensitization to gonadotrophin and may produce a substantial lowering of gonadotrophin requirement for ovulation induction in patients with large dosage needs.

Adult↗