The pleasures of home birth?
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British Columbia↗
Biomedical subjects
M A Okon
Publications and source records attributed to M A Okon.
A prospective randomized controlled study comparing two doses of gestodene in cyclic combined HRT preparations on endometrial physiology.
Postmenopausal women taking oestradiol 17-beta 2 mg daily were randomized to receive either 25 or 50 microg gestodene from day 17 to 28 of the cycle in a double-blind study. Placental protein P14 (PP14) and CA 125 concentrations in uterine flushing, endometrial morphology and irregular bleeding after 12 cycles of study were observed. Eleven and 12 women in the 25 and 50 microg groups respectively completed the study. There were no significant differences in pre-treatment biochemical and morphological indices between the groups. The median PP14 concentration increased from 332 to 5800 ng/ml (P < 0.001) and from 145 to 27 160 ng/ml (P < 0.001) in the 25 and 50 microg gestodene groups respectively. No between-group significant rise of PP14 was observed. Similarly, no significant change was seen between the initial and post-treatment concentrations of CA 125 for either group. All biopsies were atrophic at inception of the study, and both regimens produced secretory endometrial transformation in the majority of biopsies. No between-group difference was observed in the morphometric indices measured, or any significant correlation between the concentrations of PP14 or CA 125 and morphology. The mean number of days of withdrawal bleeding (3.8 and 4.2 days for 25 and 50 microg respectively) were similar. In conclusion, both regimens produced a significant rise in uterine flushing concentrations of PP14, but not CA 125. PP14 is a sensitive biochemical marker in the assessment of endometrial response to hormone replacement therapy.
Adult↗
Do androgens have a direct effect on endometrial function? An in vitro study.
OBJECTIVE: To test the hypothesis that androgens have a direct effect on the function of endometrial epithelial cells. DESIGN: In vitro study. SETTING: Academic research center. PATIENT(S): Endometrial epithelial cells were prepared from biopsy samples obtained from normal fertile women. INTERVENTIONS: Cells were incubated with androstenedione, testosterone, dihydrotestosterone, and DHEA. MAIN OUTCOME MEASURE(S): Secretion of glycodelin A into the culture fluid was used to assess secretory activity. Uptake of (3)H-thymidine and immunostaining for Ki67 was used to assess cell growth. The specific action of the androgens was confirmed by incubation with an antiandrogen, cyproterone acetate. RESULT(S): Androstenedione (10(-6) M and 10(-7) M) caused a dose-dependent decrease in glycodelin A secretion, uptake of (3)H-thymidine, and percentage of positive Ki67 cells in cultured human endometrial epithelial cells. Testosterone, dihydrotestosterone, and DHEA had no effect on glycodelin A secretion or (3)H-thymidine uptake. The direct effect of androgens on endometrial function were confirmed by demonstrating the presence of androgen receptors in cultured endometrial epithelial cells and showing that the direct effects of the androgens were not observed when cyproterone acetate was added to the cultures. CONCLUSION(S): The results suggest that androstenedione can inhibit human endometrial cell growth and secretory activity. Infertility and miscarriage associated with high androgen levels (e.g., that caused by the polycystic ovary syndrome) may be due to an adverse effect of high androgen levels on the endometrium.
Androgens↗
Metalloproteinases and tissue inhibitor of metalloproteinase 1 (TIMP-1) in endometrial flushings from pre- and post-menopausal women and from women with endometrial adenocarcinoma.
The presence of metalloproteinase activity in endometrial flushings obtained from premenopausal women, during the proliferative and secretory phases of the menstrual cycle, control post-menopausal women and women with post-menopausal bleeding (PMB) with or without adenocarcinoma was analysed by zymography. In addition, quantitative measurements of matrix metalloproteinase 2 (MMP-2), MMP-3, MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) in the flushings were obtained by ELISA. The zymography results showed eight bands of activity, with molecular weights ranging from 51 to 208 kDa in the flushings from pre-menopausal women and post-menopausal women, particularly those with adenocarcinoma. Both zymography and ELISA showed that MMP-2 and MMP-9 were the major metalloproteinases found in the flushings and only low concentrations of MMP-3 were found. Concentrations of MMP-2 in pre-menopausal women were higher in flushings obtained during the secretory phase of the menstrual cycle than those obtained in the proliferative phase (P < 0.05), suggesting that it may play a role in embryo implantation. Concentrations of MMP-2 (P < 0.001), MMP-9 (P < 0.05) and TIMP-1 (P < 0.001) in the flushings from post-menopausal control women were lower than those from pre-menopausal women. Concentrations of MMP-2 (P < 0.05) and TIMP-1 (P < 0.05) were higher in flushings from women with PMB without carcinoma compared with post-menopausal controls and concentrations of MMP-9 (P < 0.01) and TIMP-1 (P < 0.05) in flushings from women with adenocarcinoma were higher than in post-menopausal controls. Among subjects with PMB, concentrations of MMP-9 in women with adenocarcinoma were higher than those without carcinoma (P < 0.05). Our results show that concentrations of MMP-2, MMP-9 and TIMP-1, but not MMP-3, are associated with endometrial activity and, therefore, may have a role in the breakdown of endometrial tissue. In addition, the increased concentrations of MMP-9 in flushings of women with adenocarcinoma indicate that this particular proteinase is associated with the presence of endometrial neoplastic cells.
Adenocarcinoma↗
Serum leptin levels during the menstrual cycle of healthy fertile women.
Leptin is a protein, produced by adipose tissue, which has cytokine and hormonal properties. Serum leptin levels can be considered as a measure of body fat mass, and are involved in regulation of body weight. Previous studies suggest that leptin may have an additional role in reproduction, and there is also evidence for involvement in the hypothalamic-pituitary-gonadal axis. In this study, we investigate the possible changes in serum leptin concentration throughout the menstrual cycle. Samples were collected from apparently healthy, fertile women at different stages in their menstrual cycle, timed precisely according to the luteinising hormone (LH) surge. Mean serum leptin levels were significantly higher in the luteal phase (median 11.4 ng/mL) than in the follicular phase (median 10.0 ng/mL) (P < 0.001). In addition, mean serum leptin levels correlated with body mass index (r = 0.54, P < 0.05), but showed no correlation with luteal-phase progesterone levels. Results showed that levels of serum leptin vary during the menstrual cycle, and add to the mounting evidence that leptin has a role in reproduction. These fluctuations should be taken into account whenever studies are performed using female subjects.
Adult↗
Serum androgen levels in women who have recurrent miscarriages and their correlation with markers of endometrial function.
OBJECTIVE: To compare plasma androgen concentrations in women who have recurrent miscarriages and in fertile women, and to correlate the results with concentrations of the endometrial protein PP14 in uterine flushings and plasma from women who have recurrent miscarriages. DESIGN: Retrospective study. SETTING: Hospital research unit. PATIENT(S): Women attending a recurrent miscarriage clinic and normal fertile volunteers. Ten of the women with recurrent miscarriages had polycystic ovary disease (PCOD) as assessed by ultrasonography or increased follicular LH levels. INTERVENTION(S): Plasma samples were obtained from the women on days LH-7, LH-4, LH+0, and LH+7 or LH+10 of a cycle. An endometrial flushing sample and a biopsy specimen were taken from women with recurrent miscarriages on day LH+7 or LH+10. MAIN OUTCOME MEASURE(S): Androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were measured in the plasma samples. The endometrial protein PP14 was measured in the uterine flushings and in the LH+7 or LH+10 plasma samples from the women with recurrent miscarriages. RESULT(S): Testosterone concentrations were higher in the women with recurrent miscarriages both with and without PCOD on days LH-7 and LH-4 of the cycle. Concentrations of androstenedione also were higher in the women with recurrent miscarriages, but without PCOD on day LH-7. Testosterone SHBG ratios were higher in the women with recurrent miscarriages, without PCOD compared with the controls on days LH-7, LH+0, and LH+7. Mean follicular testosterone concentrations were correlated negatively with both uterine (r = -0.47) and plasma (r = -0.49) PP14 levels on day LH+10. Mean luteal phase testosterone SHBG ratios were correlated negatively with uterine PP14 concentrations on day LH+7 of the cycle (r = -0.674). CONCLUSION(S): Androgen levels are higher in women who have recurrent miscarriages than in normal fertile controls. These high levels of androgens may have a detrimental effect on endometrial function.
Abortion, Habitual↗
Is the measurement of placental protein-14 and CA-125 in plasma and uterine flushings useful in the evaluation of peri-menopausal and post-menopausal bleeding?
In this prospective study, we examined the possible diagnostic value of the measurement of two endometrial proteins, placental protein-14 (PP14) and CA-125, in the evaluation of pre- and post-menopausal bleeding. Concentrations of these two proteins were measured in plasma and uterine flushings obtained from 139 pre- and post-menopausal women with bleeding problems, and 26 normal post-menopausal control women without bleeding. Endometrial biopsy samples were also obtained for histological study. Concentrations of PP14 in both the plasma and uterine flushings in post-menopausal women were significantly lower (P < 0.001) than those of control pre-menopausal women. In post-menopausal women, the concentrations of PP14 (mean +/- SEM) in both plasma and flushing were significantly higher (P < 0.001) in women with endometrial adenocarcinoma (46.9+/-7.5 ng/ml plasma; 3350+/-1711 ng/ml flushing) than in the controls (7.6+/-1.3 ng/ml plasma; 125+/-27 ng/ml flushing) or in women with post-menopausal bleeding and atrophic endometrium (20.4+/-2.1 ng/ml plasma; 453+/-167 ng/ml flushing). In contrast CA-125 concentrations in plasma and flushings were similar in post-menopausal and pre-menopausal women. Plasma concentrations of CA-125 were higher in post-menopausal women with adenocarcinoma (29.1+/-7.4 IU/ml) than in those with post-menopausal bleeding and atrophic endometrium (21.8+/-2 IU/ml) (P < 0.05) or control post-menopausal subjects (16.1+/-2.1 IU/ml) (P < 0.01). CA-125 concentrations in uterine flushings were not significantly different in any group of post-menopausal women. The results show that concentrations of PP14 are correlated more strongly to endometrial histopathology than those of CA-125 in pre- and post-menopausal women. Elevated PP14 concentrations are also associated with the presence of endometrial adenocarcinoma and may have a potential to be used as a marker for this disease.
Adenocarcinoma↗
A prospective randomized controlled study comparing the morphological and biochemical responses of the endometrium to two different forms of 'period-free' hormone replacement therapy.
Thirty postmenopausal women were randomized to receive either continuous combined (cc) 2 mg oestradiol valerate and 0.7 mg norethisterone acetate hormone replacement therapy (HRT) daily (15 women) or tibolone 2.5 mg daily (15 women) and were monitored to determine the relationship between the two biochemical markers placental protein 14 (PP14) and the glycoprotein CA125, endometrial histology and occurrence of irregular bleeding after 12 months of treatment. The concentrations of PP14 and CA125 in plasma and uterine flushings before and after therapy were measured and their concentrations were associated with the histology of endometrial biopsies obtained on the same day as venesection and endometrial flushing. The levels of PP14 in uterine flushings were significantly increased after the administration of both types of HRT (P < 0.05 for tibolone and P < 0.001 for ccHRT). However, the concentrations of PP14 found in flushings after ccHRT were considerably greater than those found in flushings after tibolone; levels were increased about 150-fold by ccHRT and 6-fold by tibolone (P < 0.001). Plasma concentration of PP14 after both types of HRT were also significantly raised to a similar degree (P < 0.01). In contrast, the concentration of plasma and uterine CA125 were unchanged by either treatment. Histological analysis of the endometrium from women after 12 months of HRT treatment showed that 86% (6/7) of women on ccHRT had secretory activity as compared to 44% (4/9) women on tibolone (P < 0.05). Women with higher post-HRT uterine PP14 concentration were more likely to have irregular bleeding (P < 0.05). Our studies have shown that endometrial PP14 but not CA125 concentrations are raised to a significant degree by two different forms of period-free HRT regimens. Increased PP14 concentrations in uterine flushing may suggest endometrial stimulation of some form and predict the predilection to irregular bleeding. Thus uterine PP14 concentrations may be used to monitor endometrial responses in women on HRT.
CA-125 Antigen↗