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Biomedical subjects

I D Cooke

Publications and source records attributed to I D Cooke.

At least 181 records · Page 10Linked to original sources
PubMed1989

The relation between daily salivary progesterone profile and endometrial development in the luteal phase of fertile and infertile women.

This study analysed the relation between daily salivary progesterone profiles in the luteal phase and endometrial development as assessed by morphometric studies of endometrial biopsies that were timed by luteinizing hormone surge. Among 34 fertile women studied, a threshold relation was noted between cumulative salivary progesterone concentration and 11 of the 17 morphometric features measured, as well as the results of the histological dating. Above the observed threshold, a significant linear correlation was found between cumulative salivary progesterone and the results of histological dating. Among 55 women, progesterone profile in the first half of the luteal phase, but not the second half, was found to be significantly lower in those with retarded endometrial development than in those with normal development. Overall, 50% of retarded endometrial development was associated with a subnormal progesterone profile, but the other 50% was associated with a normal progesterone profile, in keeping with an abnormal response of the endometrium due to progesterone receptor deficiency. Retarded endometrial development was more likely to be associated with a subnormal progesterone profile in the first half of the luteal phase than in the second half.

Adult↗
PubMed1989

Acute effects of progesterone and the antiprogestin RU 486 on gonadotropin secretion in the follicular phase of the menstrual cycle.

Considerable controversy still exists concerning the role of progesterone in the initiation of the midcycle gonadotropin surge in humans. We, therefore, carried out a prospective randomized study to determine the potential of progesterone to initiate a gonadotropin surge and the acute effects of a potent progesterone antagonist (RU 486) on follicular phase gonadotropin secretion in normal women. The women underwent frequent blood sampling for 4 in the midfollicular (day 6) or late follicular phase (day 10). They then received either progesterone (10 mg, im) or RU 486 (10 or 100 mg, orally), and blood sampling was continued for an additional 8 h. Four women received each of the drug regimens in the early follicular phase, and four received each regimen in the late follicular phase. Two additional women were studied as control subjects at each stage of the cycle. Progesterone administration in the mid- and late follicular phases resulted in an acute increase in plasma LH and FSH concentrations, and the increases correlated with the base line plasma estradiol concentrations (P less than 0.05). In contrast to progesterone, the women who received RU 486 in the mid- and late follicular phases had a reduction in plasma LH and FSH concentrations after drug administration. The response in the mid-follicular phase was considerably less than that in the late follicular phase, and the extent of the response correlated with the baseline plasma estradiol concentrations (P less than 0.005). The changes were similar in response to both RU 486 doses. We conclude that progesterone can initiate a gonadotropin surge in the late follicular phase of the menstrual cycle. The inhibitory effect of the progesterone antagonist RU 486 suggests that a positive feedback mechanism involving progesterone may be influential some time before the surge onset.

Adult↗
PubMed1989

The medical treatment of mild endometriosis.

Minor degrees of endometriosis have often been regarded as being of no import and hence remain untreated, but a study of the natural history of endometriosis has demonstrated that 47% (95% confidence limits, 23-71%) of patients (n = 35) given placebo in a double-blind, randomized controlled trial showed progression of the disease when assessed before and after treatment by laparoscopy. The active agent, the progestogen gestrinone, was given at a dose of 2.5 mg twice weekly and resulted in an improvement of the disease (p less than 0.004). Furthermore, follow-up over 12 months showed no significant difference between those patients treated with active agent or placebo, and none between those with persistent disease and those in whom it had been obliterated. These data suggest that a diagnosis of mild endometriosis should be followed by treatment to prevent progressive disease, but that the treatment does not influence subsequent fertility. They indicate that expectant treatment has no place and that even if fertility is not an immediate requirement, active treatment should be instituted, and that the new gestogen, gestrinone is efficacious. Other treatments, such as danazol or luteinizing hormone releasing hormone (LHRH) agonists, or the older contraceptive or pseudopregnancy regimens, must be set against spontaneous improvement (in 5 of 17 patients i.e. 29%) or elimination (in 4 of 17 patients i.e. 24%) in the placebo group. Infertile patients with mild endometriosis have disorders of follicular and luteal function, and in vitro fertilization suggests a reduced fertilization rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Why does RU486 fail to prevent implantation despite success in inducing menstruation?

The administration of RU38486 (RU486) in the luteal phase may induce menstruation, but it may not be associated with shedding of the functional layer of the endometrium. This provides an explanation why, in some cases of successful menstrual induction by RU486, pregnancy continues undisturbed. The ability of RU486 to interrupt a very early pregnancy is more likely to be related to its ability to cause shedding of the endometrium than its ability to induce menstruation.

Adult↗
PubMed1988

Progressive changes in LH and FSH and LH: FSH ratio in women throughout reproductive life.

Gonadotropin secretion during the post-menopausal period is considerably higher than during the reproductive years. In this study, we present evidence that changes in the hypothalamic-pituitary-ovarian unit occur over a period of years before the onset of menstrual irregularity which heralds the menopause. FSH and LH were measured in blood samples taken on 6 days during the mid-follicular phase from 127 regularly cycling women aged between 23 and 49 yr. The women aged 23-30 yr were taken as the control group and the remainder were grouped in 2-yr age bands. A significant increase in FSH underwent a further increase in the oldest group (48-49 yr) in whom LH also became significantly elevated. The difference in the timing of the change in FSH and LH concentrations was related not only to chronological age but also to the number of years before the menopause. The increase in FSH occurred 5-6 yr pre-menopause, that in LH not until 3-4 yr before the cessation of menstruation. It is concluded that an early sign of the aging of the reproductive mechanism can be detected in women who are having normal ovulatory cycles. The regulation of FSH and LH secretion appears to be sufficiently independent to permit the observed differences in the age of onset of these premenopausal increases.

Adult↗
PubMed1988

A new method of histologic dating of human endometrium in the luteal phase.

Morphometric analysis was performed on 70 endometrial biopsy specimens collected from a population of fertile women. Of the 17 morphometric measurements that were performed on each endometrial biopsy, only 5 were required to achieve a highly significant correlation with chronologic dating based on luteinizing hormone surge (R = 0.99). The result of histologic dating, based on morphometric analysis of endometrial biopsies collected from a separate, unbiased population, correlated strongly and significantly with chronologic dating (r = 0.98, P less than 0.0001). The correlation was better than that achieved when histologic dating was performed according to the conventional dating criteria (r = 0.88, P less than 0.001).

Endometrium↗
PubMed1988

The effects of progesterone receptor blockade in the luteal phase of normal fertile women.

The effects of a single, variable dose (5 to 200 mg) of RU38486 (RU486) (Roussel-Uclaf, Paris, France) in the first half of the luteal phase of the menstrual cycle were studied in 30 normal fertile volunteers. Quantitative histologic techniques were employed, and the results were compared with normal ranges derived from a separate, normal, fertile population. It was found that RU486 inhibited glandular secretory activity, accelerated degenerative changes, induced various vascular changes, increased stromal but not glandular mitotic activity, and did not affect the predecidual reaction. The superiority of morphometric analysis over traditional dating criteria was demonstrated in this study of endometrial responses to an exogenously administered agent. In addition, it was found that temperature drop occurred in 56%, menstrual induction in 43%, luteolysis in 24%, mood change in 23%, and thirst sensation in 3% of women studied. Both menstrual induction and changes in hypothalamic function after the administration of RU486 occurred independently of luteolysis and so were likely to be the direct result of progesterone receptor blockade in these organs. Menstrual induction was significantly related to the dose given and the day on which RU486 was administered. Mood change was significantly related to the day on which RU486 was given. Most of the effects of RU486 occurred around 48 hours after its administration.

Adolescent↗
PubMed1988

The corpus luteum.

Normal corpus luteum function is determined by function in the follicular as well as the luteal phase. In the follicular phase adequate follicle-stimulating hormone (FSH) and oestrogen stimulation are required for granulosa cell mitosis and luteinizing hormone (LH) receptor synthesis. An increase in LH pulse frequency may also be necessary for adequate oestrogen synthesis and preparation of follicular cells for luteinization and secretion of progesterone. The nature of LH release may also influence luteal function and pre-ovulatory progesterone may increase the responsiveness of the follicle to gonadotrophins. The thecal vascular network becomes extensive around pre-ovulatory follicles and may influence access of gonadotrophins and/or the ability of follicular cells to respond to them. Further vascularization is an early feature of luteinization. Angiogenic factors are found in luteal tissue and prostacyclin increases luteal blood flow. The corpus luteum consists of large cells which secrete most of the progesterone and have prostaglandin F2 alpha receptors and small cells which are responsive to LH. In the luteal phase subnormal luteal function has not been associated with a reduction in LH concentration, pulse frequency or amplitude. The number and occupancy of LH receptors and adenylate cyclase activity do not appear to be altered by a reduction in luteal function. Low density lipoprotein provides the substrate and somatomedin C modulates among other hormones' influences, progesterone production. In addition to the cAMP second messenger system phosphatidyl inositol metabolism may also be associated with LH stimulation. Luteolysis is an active process; prostaglandin F2 alpha or lipoxygenase products and possibly an endogenous GnRH-like ovarian hormone may mediate it as also may oxytocin in some species.

Corpus Luteum↗
PubMed1988

An examination of the variation in timed endometrial biopsies.

Endometrial biopsies were obtained from fertile women, aged 20-40 years, with regular cycles of 25-35 days. Chronological dating of the material was carried out by determination of the luteinizing hormone (LH) peak by daily LH assay. Tissue was taken from three or four sites along the biopsy and processed for electron microscopy. Half micron thick sections were analysed by light microscopy and a morphometric examination of the glandular epithelium carried out. Nuclear size was assessed using an unbiased measuring technique and the volume density of the nucleus in the cell was also measured. A series of 12 women was examined, four at each of days LH + 2, 4 and 5. An attempt was made to control a variety of factors which contribute to the variability in the histological dating of the endometrial biopsy. In doing so it was possible to analyse the relative contributions of each sampling level to the overall variance. In contrast to earlier studies there is a relatively small intersubject variation with a correspondingly large within-biopsy variation. These results may indicate that the cellular events in the glandular epithelium, between ovulation and the middle of the luteal phase, are precisely regulated.

Adult↗
PubMed1988

The ultrastructure of the glandular epithelium in the timed endometrial biopsy.

This paper reports the electron microscopic appearance of the uterine glandular epithelium in a group of 25 women of known fertility who underwent endometrial biopsies at known times after the luteinizing hormone (LH) surge between LH + 2 and LH + 6. The use of these well-timed endometrial biopsies enables one to gain a clearer insight into the cellular dynamics of the glandular cells, between ovulation and the middle of the luteal phase. Under the influence of progesterone, the cells are transformed from relatively inactive cells full of free ribosomes to very active polarized cells, containing giant mitochondrial profiles, intracellular deposits of glycogen/glycoprotein-rich material and a complex intranuclear channel system. Intimate associations between organelles develop, the most notable being that between a semi-rough endoplasmic reticulum and the mitochondria. By taking biopsies that are accurately timed, relative to the LH surge, from a group of women of known fertility, the sequences of changes in ultrastructure are established with considerably more precision than was previously available.

Adult↗
PubMed1988

The effect of age on the cyclical patterns of plasma LH, FSH, oestradiol and progesterone in women with regular menstrual cycles.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol and progesterone concentrations in plasma were obtained daily throughout the menstrual cycles of 94 regularly cycling women, aged between 24 and 50 years. Although mean LH concentrations changed little with advancing age, mean FSH concentrations were significantly (P less than 0.001) elevated from the age of 39 years. FSH concentrations in the oldest women studied (48-50 years) were approximately 3-fold greater than in the younger controls (women aged 23-35 years). LH concentrations rose slightly (P less than 0.05) during the last 5 years only. The increase in FSH concentration was not, however, uniform across the cycle, but was confined predominantly to the mid-follicular and post-ovulatory phases (i.e. those times in the normal menstrual cycle when circulating inhibin concentrations appear to be minimal). Despite the clear increases in FSH concentration, there was little alteration in the mean steroid profiles which remained within the normal fertile range throughout the last decade of reproductive life. The only exception to this was a small, transient, but significant (P less than 0.05) decrease in preovulatory oestradiol concentration between the ages of 36 and 38 years, which was followed by a transient increase (P less than 0.01) in oestradiol concentration between 39 and 44 years. However, no corresponding significant changes in mean progesterone concentrations were observed.

Adult↗
PubMed1988

A protocol for the recruitment and screening of semen donors for an artificial insemination by donor programme.

This study outlines a structured protocol for the recruitment and screening of semen donors for an artificial insemination by donor programme. One-hundred-and-ninety-one potential semen donors were assessed. A step-wise analysis of these potential semen donors is presented, reasons for and rates of rejection at each stage are documented and explained. The majority of the potential donors were rejected on the basis of unacceptable semen analysis. A simple, structured approach to the assessment of potential semen donors is proposed.

Humans↗
PubMed1988

Sperm loss in the urine of sexually rested men.

In the majority of species, the number of spermatozoa ejaculated is considerably less than the number of sperm produced. Two possible explanations for this discrepancy are the resorption of sperm in the reproductive tract and/or the passage of sperm to the urine. We have examined 24-h urine samples from fertile men who abstained from sexual activity for up to 13 days. Very few sperm were found in the 24-h urine samples. We conclude that sperm loss in the urine is not a significant pathway of sperm disposal in the sexually rested male.

Humans↗