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Biomedical subjects

N E Reame

Publications and source records attributed to N E Reame.

At least 19 recordsLinked to original sources
PubMed2000

Concentrations of follicle-stimulating hormone correlate with alkaline phosphatase and a marker for vitamin K status in the perimenopause.

Serum alkaline phosphatase (ALP), a gross marker of bone turnover, has been reported to be elevated after menopause, a period characterized by hallmark increases in follicle-stimulating hormone (FSH). Whether the ALP rise coincides with the perimenopausal transition when changes in FSH, estrogen levels, and menstrual cycles are first apparent is not known. The purpose of this cross-sectional study was twofold: (1) to characterize the influence of the perimenopausal transition on ALP activity and (2) to correlate ALP activity with more precise markers for bone, osteocalcin (OC), and vitamin K status assessed with undercarboxylated osteocalcin (ucOC). Thirty-eight studies of hourly FSH were conducted on cycle day 6 of the follicular phase in perimenopausal women volunteers, aged 40-54 years (mean body mass index [BMI] = 24.2 +/- 0.5). Mean FSH was used to define the perimenopausal stage (early perimenopausal, mean FSH </= 15 IU/L, n = 27; late perimenopausal, mean FSH > 15 IU/L, n = 11). As expected, late perimenopausal women had irregular and longer menstrual cycles, lower estradiol (E(2)) and estrone (E(1)) levels, and a lower frequency of ovulations vs. the early group. ALP was higher (76.5 +/- 8.3 vs. 58.3 +/- 2.7 IU/L, p = 0.045) compared with the early perimenopausal group. In a subsample (n = 10), OC was associated with ALP (r = 0.69, p < 0.03), FSH was positively related to ucOC concentrations (r = 0.7, p < 0.03), and women with E(1) concentrations <40 pg/ml had double the percentage of ucOC compared with those where E(1) was >40 pg/ml (46.3% +/- 6.6% vs. 22.0% +/- 3. 1%, p < 0.006). Clinical markers of the perimenopause are associated with a nonspecific but inexpensive marker of enhanced bone turnover (i.e., higher ALP) and correlate well with more precise markers of bone activity. These findings suggest that health-promotion strategies for preserving bone should be instituted well before the last menstrual period.

Adult↗
PubMed1998

A two-site chemiluminescent assay for activin-free follistatin reveals that most follistatin circulating in men and normal cycling women is in an activin-bound state.

Follistatin (FS) is a monomeric protein that binds and regulates the bioavailability of activin. Previously, we found circulating levels of total FS to be similar in men and cycling women. Because relative amounts of activin-bound and free FS are important considerations in determining activin bioavailability, we asked here whether the relative proportions of these two changed during different physiologic states. For this, we developed a two-site, solid-phase, immunochemiluminescent assay for free FS. The assay recognizes the 288 or 315 amino acid variants of human FS and has a detectable limit of 1 ng/mL. Inhibin, transforming growth factor-beta, or alpha-2-macroglobulin do not cross-react or interfere in this assay. Preincubation of FS with activin results in dose-dependent loss of immunoreactivity, confirming specificity of the assay for free FS. Human follicular fluid, pituitary extract, and serum with added FS dilute parallel with the recombinant human FS-288 standard. Recovery of recombinant human FS-288 from serum is quantitative. Using this assay, we found circulating concentrations of free FS to be at or below the detection limit of the assay throughout the menstrual cycle. Comparison of circulating total and free FS levels in postmenopausal or cycling women and normal men suggested that at least 90% is activin-bound. In contrast, measurable quantities of free FS were found in follicular fluid and pituitary extracts. The results of this study, showing that most circulating FS is normally activin-bound, argue against an endocrine role for FS and suggest that a major role of circulating FS is to bind and neutralize the bioactivity of circulating activin. The roles of FS as a local autocrine or paracrine regulator of activin in target tissues, where FS exists in free form, or as an endocrine regulator in human pathophysiology, warrants further investigation.

Activins↗
PubMed1998

Net increase in stimulatory input resulting from a decrease in inhibin B and an increase in activin A may contribute in part to the rise in follicular phase follicle-stimulating hormone of aging cycling women.

Recent studies suggest that an age-related decline in ovarian inhibin B may play a role in the increase in follicular phase FSH in menstrual cycles of older women. Considering that the peripheral feedback regulation of FSH is dictated by the overall tone of inhibins, activins, and follistatins as well as estradiol, it is essential to determine the relative inputs of all of these regulators in assessing whether the collective peripheral input to FSH is one of inhibition or stimulation. To test the hypothesis that changes in the overall tone of peripheral feedback may contribute to this hallmark sign of aging, we compared the concentrations of dimeric inhibin A, inhibin B, activin A, and total and free follistatin in 7 young (mean age, 27.9 +/- 2.6 yr) and 10 older (mean age, 43.6 +/- 0.9 yr) cycling women during the follicular (FOLL; cycle day 6) and midluteal (ML; 7 days post-LH surge) phases of the menstrual cycle. Subjects were preselected on the basis of FOLL phase FSH levels (older, > or = 8.0 mIU/mL; younger, < 8 mIU/mL). Circulating FSH regulatory peptide concentrations were determined from samples pooled from blood drawn every 10 min for 8 daytime h using specific 2-site assays. In the older group, cycle length was shorter (29.1 +/- 0.5 vs. 26.1 +/- 0.5, young vs. older; P < 0.001), mean LH levels during the follicular phase were higher (LH, 5.6 +/- 0.8 vs. 8.8 +/- 1.1 mIU/mL, young vs. older; P < 0.001). Mean FSH levels for the older and younger groups averaged 10.8 +/- 0.8 and 6.2 +/- 0.3 mIU/mL, respectively. Estradiol levels were higher, but not statistically different, than those in the younger group (99 +/- 13 vs. 169 +/- 25 pmol/L, young vs. older; P = 0.06). In both age groups, inhibin B levels were higher in the FOLL vs. ML phase, inhibin A levels were higher in the ML vs. FOLL phase, but total activin A and total and free follistatin did not differ across cycle days. FOLL phase inhibin A levels were higher in the older group (16.3 +/- 2.4 vs. 26.4 +/- 3.4 pg/mL, young vs. older; P = 0.024), but levels of inhibin B were lower (323 +/- 80 vs. 163 +/- 24 pg/mL, young vs. older; P = 0.03). Overall, the estimated total inhibin activity (inhibin A plus inhibin B) was lower in older cycling than in younger women (339 +/- 82 and 189 +/- 24 pg/mL, young vs. older). Total and free follistatin levels were not different among the 2 groups of women. In contrast, total activin A levels were higher in the older cycling group (0.51 +/- 0.05 and 0.68 +/- 0.05 ng/mL, young vs. older; P = 0.02). No differences in age groups were observed during the ML phase for any of the variables measured. These data suggest that a net increase in stimulatory input resulting from a decrease in inhibin B and an increase in activin A may contribute in part to the monotropic FSH increase in aging women.

Activins↗
PubMed1997

Intensive hormone monitoring in women with unexplained infertility: evidence for subtle abnormalities suggestive of diminished ovarian reserve.

OBJECTIVE: To determine hormone levels across the menstrual cycle in women with rigorously defined unexplained infertility. DESIGN: Prospective study. SETTING: National Center for Infertility Research at Michigan. PATIENT(S): Evaluation of 1,885 women with infertility identified 12 women who met the following rigorously defined criteria for unexplained infertility: [1] infertility of > or = 24 months' duration, with no male factor, anatomic or functional disorders of the reproductive tract, or immunologic infertility; [2] normal body mass index (BMI); (3) ovulatory cycles ranging from 26 to 32 days; [4] normal luteal phase determined by endometrial biopsy; and [5] normal baseline hormonal profile. Controls (n = 12) were healthy, parous women with normal ovulatory cycles and normal hormonal screens, and were matched for age and BMI with patients. MAIN OUTCOME MEASURE(S): Daily gonadotropin and steroid hormone levels across the menstrual cycle. RESULT(S): Basal FSH and LH levels in the early, middle and late follicular phases were increased significantly in the group with unexplained fertility compared with the normal controls. The mean (+/-SD) early follicular FSH levels were 7.0 +/- 0.57 mIU/mL in the unexplained-infertility group and 4.7 +/- 0.37 mIU/mL (conversion factor to SI units, 1.00) in the normal controls, respectively. There was no difference between groups over the periovulatory or luteal phase. Midluteal mean (+/-SD) P levels were lower in the unexplained-infertility group than in the normal controls (13.7 +/- 1.6 versus 24.0 +/- 3.2 ng/mL [conversion factor to SI units, 3.180]). Mean E2 concentrations were elevated in the group with unexplained infertility versus normal controls in the early through the late follicular phase but reached significance only in the midfollicular phase. Mean prolactin levels were elevated consistently across the menstrual cycle in the unexplained-infertility group compared with those in normal controls but reached significance only in the early and late follicular and midluteal phases of the cycle. Cortisol concentrations were similar between the two groups. CONCLUSION(S): These data indicate that there are subtle alterations in various hormones measured across the menstrual cycle in women with unexplained infertility compared with those in normal controls, suggesting a diminished ovarian reserve.

Adult↗
PubMed1996

Age effects of follicle-stimulating hormone and pulsatile luteinizing hormone secretion across the menstrual cycle of premenopausal women.

To characterize the differential aging response in gonadotropin secretion that occurs before menopause, we assessed pulsatile LH and serial FSH, estradiol (E2), and progesterone (P) concentrations in aging women across the menstrual cycle. We conducted 96 daytime studies during the follicular, midluteal, and late luteal phases of the same menstrual cycle in 32 volunteers, aged 40-50 yr (n = 16) and 19-39 yr (n = 16). Mean cycle length was shorter in the older women (26 +/- 0.4 vs. 27.6 +/- 0.6 days; P = 0.02), but mean plasma E2 and P values were similar in the two age groups. Mean plasma FSH was higher in the older group on all 3 study days. For LH, an age difference was observed during the late luteal phase, when mean plasma LH and pulse amplitude were higher in women over 40 yr of age (mean LH, 6.4 +/- 0.7 vs. 3.0 +/- 0.5 IU/L (P = 0.002); mean amplitude, 4.0 +/- 0.5 vs. 2.8 +/- 0.2 IU/L (P = 0.03)]. Pulse frequency was higher in the older group, but not different from that in younger women on all study days. When the subjects aged 35-39 yr were analyzed as a third age group (n = 8), age effects for mean LH persisted, and pulse frequency was higher in the group over 40 yr of age vs. women under age 35 yr (n = 8) in both the follicular phase (7.1 +/- 0.4 us. 5.6 +/- 0.8; P = 0.03) and late luteal phase (5.8 +/- 0.7 vs. 4.4 +/- 0.3; P = 0.03). Although highly variable, individual patterns of gonadotropin secretion in the women over age 40 yr included a sustained elevation in the FSH/LH ratio as well as a failure to demonstrate slow frequency, high amplitude LH pulses in the midluteal phase. In conclusion, 1) the age-related increase in FSH concentrations in ovulatory women, although more pronounced, is associated with phase-dependent enhancement of pulsatile LH secretion; 2) the higher LH concentrations are brought about by changes in both pulse frequency and amplitude; and 3) these age effects preempt overt reductions in cyclic E2 or P concentrations.

Adolescent↗
PubMed1992

A prospective study of the menstrual cycle and spinal cord injury.

Sixty seven menstrual cycles were studied prospectively in a nonclinical sample of 20 women who had suffered a traumatic spinal cord injury (quadriplegia n = 13; paraplegia n = 7) at least 1 yr before assessment. Level of injury did not influence cycle length (mean +/- SE = 28.7 +/- 3 days), duration of menses (4.6 +/- 1 days) or serum concentrations of gonadotropins and ovarian hormones. Midluteal phase serum progesterone values were consistent with ovulation (progesterone = greater than 5 ng/ml) in 93% of the cycles in which endocrine measures were obtained; but the ability of basal body temperature pattern to predict serum progesterone was low (43%). Cyclic dysmenorrhea was reported by 13 women with injuries ranging from C5 to T12. These findings suggest that ovulatory menstrual cycles are common in women after traumatic spinal cord injury and support the need for contraception by those wishing to avoid pregnancy. Basal body temperature charts revealed potential problems in applying the symptothermal method of natural family planning to a population of women at risk for oral contraceptives.

Adult↗
PubMed1990

Surrogate pregnancy: clinical features of forty-four cases.

This record analysis describes the obstetric outcomes of a series of 44 pregnancies occurring in 41 women who underwent donor insemination as participants in a private surrogate parenting program between 1981 and 1985. The typical surrogate mother was 25 years old with a high school education and married with one child 2 years old. Twenty-nine percent of the sample reported no source of income other than welfare. Two thirds of the histories included at least one of the following perinatal risk factors: smoking (n = 19), low annual income (n = 15), unmarried status (n = 12), or parity of 0 or greater than 4 (n = 5). Six losses occurred in the first or second trimester. Thirty-nine viable infants were born to 37 women and include one set of fraternal twins. Three of the singleton newborns weighed less than 2500 gm; newborn morbidity after preterm delivery occurred in one case. Women with complications (n = 14) were similar in maternal age, education, parity, annual income, marital status, and smoking history to women without complications (n = 24). A role for psychosocial stress and financial motivation in the etiology of these outcomes is explored.

Adult↗
PubMed1989

The lesbian childbearing experience: assessing developmental tasks.

Selected nursing theories about the childbearing experience are examined as they apply to the assessment of the pregnant lesbian couple. A review of the women's health literature suggests that the lesbian pregnancy experience is characterized by the use of donor insemination, social discrimination and a dependence on peer rather than family networks for social support. Based on these sociocultural constraints, the authors propose that the lesbian couple is faced with greater barriers than are heterosexual parents to achieving the developmental tasks of "safe passage" and acceptance by others of the pregnancy. Future research should document how a lesbian identity affects the pregnant woman's relationship with her mother, her partner's psychosocial development as a parent and the maternal-infant attachment process. Nursing guidelines for assessing parental role development are presented.

Attitude of Health Personnel↗
PubMed1989

The roles of estradiol and progesterone in decreasing luteinizing hormone pulse frequency in the luteal phase of the menstrual cycle.

During the luteal phase of the menstrual cycle, plasma progesterone (P) and estradiol (E2) concentrations are elevated, and LH (and by inference GnRH) pulse frequency is slow. In contrast, LH pulse frequency increases during the early follicular phase when plasma E2 and P are lower. To examine the mechanism(s) responsible for the slower GnRH pulse frequency in the luteal phase, we maintained plasma P, E2, or both at midluteal concentrations from the midluteal phase to the time of the next early follicular phase and measured the effects on LH secretion. Thirteen normal women with regular menstrual cycles were studied during two or three cycles. Blood was obtained every 10 min during 10-h studies. Control cycle luteal and early follicular studies were followed by a second control study in the luteal phase of the treatment cycle. P (six women), E2 (seven women), or both (five women) then were given twice daily by im injection for 6-12 days until the day corresponding to the early follicular study of the control cycle (EF + P, EF + E2, or EF + E2 + P). A final study was performed 1 week after the injections were discontinued (F). LH pulse frequency was low in the midluteal phase [3.2 +/- 0.2 (+/- SE) pulses/10 h] and increased by the early follicular phase (8.0 +/- 0.8 pulses/10 h) in the control cycles. The increase in LH pulse frequency was not significantly inhibited by administration of P (6.7 +/- 0.7 pulses/10 h; EF + P). However, during both E2 alone and E2 + P, LH pulse frequency remained low (EF + E2, 3.6 +/- 0.8; EF + E2 + P, 2.0 +/- 0.7 pulses/10 h). The mean plasma FSH concentrations paralleled changes in LH pulse frequency, increasing from the luteal to the early follicular phase in the control cycles and during P injections and remaining low during E2 and E2 + P injections. We conclude that continued exposure to P alone does not maintain GnRH pulse frequency at midluteal phase values and that any effect of P requires the presence of E2. As E2 alone maintained lower LH pulse frequency, E2 may act directly to decrease the pulsatile GnRH secretion or it may potentiate the effects of low (less than 3.2 nmol/L) P concentrations.

Adult↗
PubMed1987

Diurnal patterns of pulsatile luteinizing hormone secretion in hypothalamic amenorrhea: reproducibility and responses to opiate blockade and an alpha 2-adrenergic agonist.

The pattern of pulsatile GnRH secretion is abnormal in some women with hypothalamic amenorrhea (HA) consequent to previous exercise or weight loss. Both diminished frequency pulsatile LH secretion, and by inference GnRH secretion, and normal LH pulsatility have been reported. We assessed whether the patterns of GnRH secretion varied with time by measuring plasma LH every 15 or 20 min for 24 h on 1-3 occasions during a 10-month period in 14 women with HA (a total of 24 studies). During the day, mean LH pulse frequency [1.0 +/- 0.1 (+/- SE) pulses/8 h] was lower than that in normal women in the early follicular phase of their cycles (5.1 +/- 0.6), and the frequency in individual HA patients was lower than early follicular phase values in 16 of 17 studies. The slow daytime LH pulse frequency also was a consistent finding, in that the values in repeat studies varied by less than 2 pulses/8 h in all but 1 patient. LH pulse frequency (2.0 +/- 0.4 pulses/8 h) was higher and more variable during sleep, and normal early follicular phase frequencies were found in 20% of patients with HA. The mechanisms whereby GnRH pulse frequency is reduced are not known. alpha-Adrenergic agonist drugs stimulate GnRH pulsatile secretion in rodents, but administration of the alpha 2-agonist clonidine (0.15 mg, orally, at 0800 and 2000 h) did not increase the frequency of LH pulses in 7 women (1.7 +/- 0.4 pulses/8 h). In contrast, administration of naloxone (1 mg/m2 X h, iv) for 8 h during the day to 14 patients, increased LH pulse frequency (3.3 +/- 0.5 pulses/8 h). In 8 of these 14 women, LH pulse frequency (4.9 +/- 0.4 pulses/8 h) increased into the range found during the normal early follicular phase, while in the other 6 women pulse frequency was not significantly increased (1.4 +/- 0.4 pulses/8 h). Plasma estradiol levels were similar in naloxone-responsive and unresponsive women, but spontaneous LH pulse frequency was higher at night in naloxone-responsive patients (2.9 +/- 0.6 vs. 1.4 +/- 0.3 pulses/8 h). The presence of nocturnal LH pulses did not predict responsiveness to naloxone, however, and LH pulse frequency was less than 2 pulses/8 h in 4 of the women who responded to naloxone. These data indicate that slow frequency GnRH secretion is a common finding during the day in women with HA. GnRH secretion is more variable at night, suggesting that the mechanisms involved in reducing pulsatile GnRH secretion are less effective during sleep.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1985

Pulsatile gonadotropin secretion in women with hypothalamic amenorrhea: evidence that reduced frequency of gonadotropin-releasing hormone secretion is the mechanism of persistent anovulation.

Hypothalamic amenorrhea (HA) is a clinical disorder of unknown etiology. The diagnosis is made by exclusion of known abnormalities of pituitary and ovarian function. To determine if abnormalities of GnRH secretion could account for the anovulation and amenorrhea, we measured plasma gonadotropins every 20 min for 10- to 24-h periods in 19 women with HA. Ovarian steroids and gonadotropin responses to an iv bolus dose of GnRH (25 ng/kg) were also measured. The results were compared to those obtained during the early follicular (EF) and late luteal (LL) phases of ovulatory cycles in normal women. Plasma estradiol was lower (mean +/- SE, 52 +/- 5 pg/ml) than either cycle stage in normal women. Mean plasma LH was lower than EF values and FSH was higher than LL values. The amplitude of LH pulses in HA was similar to that in normal women. LH pulse frequency was the same as that present during the LL, but lower than that during the EF (HA, 4.7 pulses/12 h; EF, 7.7 pulses/12 h; P less than 0.05). In addition to the similar frequency, the patterns of LH secretion in HA resembled that of LL in that the amplitude of LH pulses was highly variable and pulses occurred at irregular intervals. Consistent changes in diurnal gonadotropin secretion were not found, and LH secretion was greater at night in 9 studies and during the day in 5 studies. Repeat studies in three patients (5-13 months later) revealed that LH pulse frequency was variable, being unchanged in 1, increased in 1, and decreased in the third patient. Thus, LH pulse frequency and, by inference, GnRH pulse frequency are similar in HA to those in the normal luteal phase despite a different steroid milieu. GnRH pulse frequency increases from the luteal to the follicular phases of normal cycles and may be important in the initiation of ovarian follicular maturation. These data suggest that the absence of cyclical gonadotropin secretion and anovulation in HA result from a decreased frequency and irregular amplitude of GnRH secretion and consequent absence of ovarian follicular maturation.

Adolescent↗
PubMed1985

Idiopathic hypogonadotropic hypogonadism in men: dependence of the hormone responses to gonadotropin-releasing hormone (GnRH) on the magnitude of the endogenous GnRH secretory defect.

Idiopathic isolated gonadotropin deficiency (IGD) is associated with a spectrum of clinical findings as well as variable gonadotropin responses to GnRH. In this study we investigated whether patterns of gonadotropin and testosterone responses to pulsatile GnRH therapy (25 ng/kg, iv, every 2 h for 4 days) were related to the magnitude of the GnRH secretory defect in patients with IGD. Eight men with IGD were studied. Patients with partial IGD (p-IGD) and those who had no evidence of GnRH secretion (n-IGD) were differentiated by the presence or absence of spontaneous LH secretory pulses during 24 h of every 20-min blood sampling. In response to the first GnRH injection, no LH rise occurred in the n-IGD patients, while LH increases in the p-IGD patients were similar to those in normal men. Continuation of GnRH therapy in patients with n-IGD resulted in predominant FSH secretion and absent or minimal augmentation of LH and T secretion. In contrast, predominant LH secretion occurred in the p-IGD patients and resulted in a significant increase in serum testosterone. A bolus dose of GnRH 2 days after the termination of GnRH therapy caused significant augmentation of gonadotropin responses in the n-IGD, while in the p-IGD group, both LH and FSH responses were unchanged compared to those after the first GnRH pulse. These results indicate that IGD is characterized by variable degrees of endogenous GnRH deficiency. Moreover, the hormone responses to GnRH in IGD patients depend on the magnitude of the underlying GnRH secretory defect.

Adolescent↗
PubMedDate not supplied

Pulsatile LH secretion in women with premenstrual syndrome (PMS): evidence for normal neuroregulation of the menstrual cycle.

The premenstrual syndrome (PMS) has been proposed to result from excessive exposure to and/or withdrawal of brain opioid activity during the luteal phase. Because hypothalamic opioids are believed to modulate GnRH secretion, in part under the influence of ovarian steroids, we performed longitudinal studies of gonadotropin and ovarian steroid secretion across ovulatory, symptomatic cycles of 17 PMS patients and 8 normal volunteers. Pulsatile LH secretion was measured every 10 min for 8 hr at times when central opioid activity was expected to be low (early follicular phase), high (mid-luteal phase; ML), and declining (late luteal phase). In both subject groups, a cycle-phase effect was observed for LH pulse frequency (p = < 0.001) and amplitude (p = 0.002), and for the transverse mean concentrations of LH (p = 0.05), FSH (p < = 0.001), estradiol (E2) (p = < 0.001) and progesterone (P) (p = < 0.001). ML P secretion in PMS patients was pulsatile, and mean concentrations (over 30-60 min) were similar to those of normal controls. The changes in pulsatile LH secretion across the cycle were not different in the PMS patients compared to the normal women, though mean FSH in the ML phase was higher in the PMS group (p = < 0.05). The similar changes in luteal LH pulse frequency fail to provide evidence that GnRH secretion is impaired, thus challenging the view that the neuroregulation of the menstrual cycle in women with PMS is markedly altered.

Adult↗