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Biomedical subjects

M G Metcalf

Publications and source records attributed to M G Metcalf.

At least 37 records · Page 2Linked to original sources

Gonadotrophin excretion in fertile women: effect of age and the onset of the menopausal transition.

In normal women the menopausal transition starts typically with a sudden break in regular menstrual cyclicity: gonadotrophin levels escape from the cyclical pattern characteristic of fertile women and increasingly rise into the postmenopausal range. An investigation was undertaken to determine whether this rise precedes the first appearance of ovarian dysfunction. Weekly urine samples for the measurement of FSH, LH and pregnanediol were collected from 100 women, all of whom had regular 20- to 35-day menstrual cycles (504 samples from 48 women aged 20-39 years and 620 samples from 52 women aged 40-48 years; 96.8% of these cycles were shown to be ovulatory). Excretion rates of FSH in excess of 5 i.u./24 h occurred more often in women aged greater than or equal to 40 years than in younger women (incidence, 31.5 cf. 19.5%; P less than 0.001). The difference was greatest at the time of the perimenstruum (7-day incidence, 32.5 cf. 13.9%) and declined to insignificance during the mid-cycle gonadotrophin surge (7-day incidence, 44.2 cf. 34.8%). Examination of the rank correlation between age and gonadotrophin excretion confirmed the age-related rise in FSH and identified a lesser but significant perimenstrual rise in LH. For both FSH and LH these changes were small compared with the increases observed in nine women presumed to have reached the menopausal transition during the trial (incidence FSH greater than or equal to 5 i.u./24 h, 60.6%; incidence LH greater than or equal to 5 i.u./24 h, 48.6%). It is concluded that in fertile women there is evidence of an age-related rise in FSH which is distinct from the changes occurring at the start of the menopausal transition.

Adult↗

Indices of ovulation: comparison of plasma and salivary levels of progesterone with urinary pregnanediol.

An increased daily excretion of pregnanediol, relative to that early in the menstrual cycle, is often taken to be evidence that a woman has ovulated. This paper assesses the value of alternative procedures for this purpose. Urine, plasma and saliva samples were collected during a 24-h period from 20 women during the follicular phase and from 20 women during the luteal phase. The 24-h excretion of pregnanediol was compared with (1) the concentration of progesterone in plasma, (2) the concentration of progesterone in saliva, (3) the concentration of pregnanediol in small urine samples, (4) the rate of excretion of pregnanediol and (5) the ratio of pregnanediol to creatinine in small urine samples. Each analyte increased substantially during the luteal phase. The median increases (ratio of luteal to follicular phase values) were 14.8, 3.2, 10.6, 11.9 and 11.1 respectively. By comparison, the median increase in 24-h pregnanediol output was 9.2. When the other analytes were used instead of the 24-h excretion of pregnanediol to assess the possibility of ovulation, the incidence of misclassifications (follicular samples classed as luteal and luteal samples classed as follicular) was 0, 12.8, 5.9, 2.0 and 1.0% respectively. It was concluded that the most satisfactory alternative to the measurement of 24-h pregnanediol output for the biochemical assessment of ovulation based on progesterone production was the measurement of the concentration of progesterone in plasma; the least satisfactory alternative was determination of the concentration of progesterone in saliva. If blood was not available, measurement of the ratio of pregnanediol to creatinine in a small urine sample was the preferred method.

Adult↗

Incidence of ovulation from the menarche to the menopause: observations of 622 New Zealand women.

Urine samples were collected once weekly for two to four months from 622 normal women. Menstrual cycles were considered to be ovulatory if the 24 h pregnanediol output in the 12 days preceding menstruation was greater than or equal to 5 mumol on one occasion, or if the total excreted on two occasions, one week apart, was greater than or equal to 7 mumol. The incidence of ovulatory cycles increased from 48% in girls aged 10-14 yr to 72% by 20-24 yr, reached a plateau of 98% in women aged 30-39 yr, then declined with the approach of the menopause to 66% in women over the age of 50 yr. In women who were 5-8 yr from the menarche, departure from the parental home was associated with a decline in ovulatory incidence (84% for women living with parents, cf 46% for women living in flats and hostels; p less than 0.01). A similar decline was noted in women over the age of 40 yr who had experienced a break in a previously regular pattern of menstrual cycles (98% for women with regular cyclicity, cf 58% for women with variable cyclicity; p less than 0.001). Hormone patterns consistent with the occurrence of ovulation were seen at all stages from 120 days after the menarche to seven days before the menopause.

Adolescent↗

Incidence of ovulation in the years after the menarche.

Urine for the analysis of pregnanediol was collected weekly for 3 months from 209 menstruant women aged 11-24 years who lived with their parents and from 59 women aged 17-23 years who had left the parental home. Menstrual cycles were classed as ovulatory if the 24-h pregnanediol output in the 12 days preceding menstruation was greater than or equal to 5 mumol on a single occasion or if the total excreted on 2 days, 1 week apart, was greater than or equal to 7 mumol. In the first group, ovulatory incidence increased with menarchal age. Unfailing ovulation occurred in 22.9, 25.0, 44.8, 42.9, 63.2, 71.8 and 82.6% of those who were less than 1, 1- less than 2, 2- less than 3, 3- less than 4, 4- less than 5, 5-8 and 9-12 years from menarche. Comparable figures for the women who lived in flats and hostels were 40.0% (menarchal age, 5-8 years) and 78.6% (9-12 years). It is concluded that a regular pattern of ovulatory menstrual cycles is established in most young women within 5 years of the menarche, and that departure from the family home is often associated with a regression to a juvenile pattern of anovulatory menstrual cycles.

Adolescent↗

Glycerol prevents loss of immunoreactive follicle-stimulating hormone and luteinizing hormone from frozen urine.

First morning urine samples were collected from both menstruant and post-menopausal women and stored at -25 degrees C. Immunoreactive FSH disappeared from these samples (t1/2 = 30 days), ultimately stabilizing at about 20% of the initial value. The loss was more rapid at -20 degrees C and less rapid at -55 degrees C and +4 degrees C. Immunoreactive LH was also lost from frozen urine, but more slowly than FSH. The addition of glycerol to urine (0.52 mol/l) stored at -25 degrees C prevented loss of immunoreactive FSH and LH for at least 105 days.

Drug Stability↗

Pituitary-ovarian function before, during and after the menopause: a longitudinal study.

The excretion of FSH, LH, oestrogens and pregnanediol was monitored once weekly in urine samples collected from eight peri-menopausal women aged 44-55 years (median, 52 years). Observations were commenced between 5 and 15 weeks before the menopause and were continued for 22-30 weeks after final menstruation. Amenorrhoea of greater than 2 years duration in association with a persistent elevation in gonadotrophin output was considered proof of the post-menopausal state. No clear hormonal change occurred at the time of the menopause. During the peri-menopause there is a transition from the regular ovulatory cycles of pre-menopausal women to the unvarying high gonadotrophin and low oestrogen excretion which is generally regarded as being characteristic of post-menopausal women. In the group studied, post-menopausal levels of FSH and LH were common before and episodes of high oestrogen excretion were not uncommon after final menstruation. Menstrual failure appeared to occur spontaneously at some stage during the transition from the pre- to the post-menopausal state, and not to be associated with its conclusion. From the hormonal point of view the immediately post-menopausal period could not be distinguished from the long cycles of peri-menopausal women. This suggests that an endometrial rather than a hormonal event might determine the time at which menstruation stops during the menopausal transition.

Adult↗

Estimation of viability of bovine granulosa cells.

Granulosa cells harvested from non-atretic, antral follicles of cow (and pig and sheep) ovaries were incubated over glass cover slips in medium containing 20% (v/v) donor calf serum. Cell attachment to the cover slips was rapid, being in most cases complete within 3 h at 37 degrees C. There was little further change over the next 20 h. The number of bovine granulosa cells which attached to a cover slip was proportional to the volume of cell suspension added to the medium; and the amount of oestradiol secretion by attached cells in a testosterone-enriched medium increased in parallel with their number. Granulosa cells which did not attach within 3 h produced little oestradiol. There was no clear relationship between the number of nigrosin-impermeable cells in suspensions prepared from different follicles and plating efficiency. It is concluded that the 3-h attachment of granulosa cells in culture is a useful measure of the number of viable cells in a suspension and is to be preferred to less direct techniques based on dye exclusion.

Animals↗

Pituitary-ovarian function in normal women during the menopausal transition.

The excretion of follicle stimulating hormone (FSH), luteinizing hormone (LH), oestrogens and pregnanediol was measured in weekly urine samples collected for 14-87 weeks (median, 43 weeks) from thirty-one perimenopausal women aged 36-55 years (median, 50 years). The results were compared with those found in twenty-two postmenopausal women aged 55.4 +/- 5.4 years (mean +/- SD), and in twenty premenopausal women aged 44.4 +/- 3.4 years with regular, ovulatory, menstrual cycles. Women classed as perimenopausal had a recent history of irregular menstrual cycles following regular cyclicity. The hormone patterns observed in the perimenopausal women varied widely, both between individuals and from time to time in the same individual. They ranged from ovulatory cycles with low premenopausal levels of FSH, to transient episodes indistinguishable from those found in postmenopausal women with high levels of FSH and LH. Between these extremes were patterns rarely seen at other times in reproductive life: namely, (1) in fourteen women on thirty-two occasions lasting 2-9 weeks, postmenopausal levels of FSH and LH occurred in association with high oestrogen levels; (2) in eighteen women on thirty occasions lasting 2-8 weeks, there was an elevation of LH (but not FSH) into the postmenopausal range; (3) in thirteen women on twenty-six occasions lasting 1-2 weeks, there was an elevation of FSH (but not LH) into the postmenopausal range. These patterns were not seen in any of the premenopausal women. Typically, the approach of the menopause was marked by an increased incidence of high postmenopausal levels of FSH and LH. Ovulatory cycles were observed at all stages in the perimenopause, and occurred within 16 weeks of the last menstrual period in seven of the thirteen women who became postmenopausal during the study. It is concluded that the appearance of high levels of FSH and LH is characteristic of the perimenopause and often precedes the sustained loss of sex hormone secretion by the ageing ovary. Postmenopausal biochemical parameters are no guarantee of the postmenopausal state.

Adult↗

Use of small samples of urine to monitor gonadotrophins in menopausal women.

The increased gonadotrophin secretion which occurs at the menopause was followed by measuring gonadotrophin to creatinine ratios in small samples of urine. For follicle stimulating hormone, values of the ratio corresponded closely with both plasma concentration (correlation coefficients: 0.93, 0.94 and 0.93 for first morning, mid-morning and mid-afternoon urine samples: all results expressed as logarithms) and 24-h urine output (0.98, 0.96 and 0.94). Comparable figures for luteinising hormone (LH) were 0.94, 0.94 and 0.90; and 0.95, 0.95 and 0.90. Multiplication of the gonadotrophin to creatinine ratios (I.U./mmol) by 10 gave a figure close to 24-h gonadotrophin output (I.U.).

Adult↗

Fluctuating ovarian function in a perimenopausal women.

Plasma follicle stimulating hormone (FSH) and luteinising hormone (LH) concentrations, and pregnanediol and oestrogen excretion rates, were measured in a perimenopausal woman from the first appearance of oligomenorrhoea until the onset of severe and persistent hot flushes two years later. Postmenopausal episodes characterised by hot flashes, amenorrhoea, high FSH levels (greater than or equal to 5IU/L) and low urinary oestrogens (less than or equal to 50 nmol/24hr), were followed by menstrual cycles in which the FSH levels were low (less than 5 IU/L) and there was an ovulatory pattern of oestrogen and pregnanediol excretion. An unusual association of high urinary oestrogens (greater than or equal to 50 nmol/24hr) with high gonadotrophin levels was observed on several occasions. The transient postmenopausal episodes were biochemically and symptomatically indistinguishable from the permanent amenorrhoea of postmenopausal women.

Climacteric↗

Lack of effect of prolactin suppression on plasma dehydroepiandrosterone sulphate.

In twelve patients with hyperprolactinaemia, treatment which reduced plasma prolactin from a mean of 531 microgram/l (range 68-3500 microgram/1) to 8.3 microgram/l (0-27 microgram/l), caused no significant change in plasma dehydroepiandrosterone sulphate (DHA-SO4). Pre-treatment levels of DHA-SO4 were within the normal range in eleven out of twelve cases. The results do not support for claims that prolactin excess is associated with an increase in circulating DHA-SO4.

Adolescent↗

Use of a sulfate: hydrogen sulfate buffer to preserve urine for steroid analysis.

1. HCI, commonly used to preserve urine for steroid analysis, cannot safely be supplied to out of town patients. 2. An equimolar mixture of Na2SO4 and NaHSO4 is a safe alternative which may be used to protect specimens en route to the laboratory. 3. Addition of bisulfate buffer to urine (20 g/l) reduced the pH to 2.0-3.5 (31 specimens; 24 hr urine volumes, 560-3320 ml). 4. Little change in pH was observed when buffered urine (12 specimens) was kept at 30 degrees for 14 days (initial pH 2.62 +/- 0.38 (mean +/- standard deviation); PH after 14 days, 2.59 +/- 0.48). 5. Analysis of the creatinine, 17-oxosteroids, 17-oxogenicsteroids, estrogens, pregnanediol, androsterone + etiocholanolone and estriol in urine samples acidified to pH 2-3 with HCl, and in the same samples acidified with buffer, gave results which were indistinguishable from each other. 6. Almost no change in steroid and creatinine concentrations was observed in samples of buffered urine kept for 10 days at room temperature (20-26 degrees).

Buffers↗