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Progesterone in human parturition: progesterone and 5α-pregnane-3,20-dione in relation to human myometrial activity
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
1991 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This study was undertaken to evaluate the relationship of progesterone and 5α-pregnane-3,20-dione (5αDHP), a major progesterone metabolite, to human parturition. The serum concentrations of 5αDHP prior to, during and following parturition were to be established, as well as its maternal and fetal concentration in different modes of delivery. Some of its effects in vitro were also to be studied. Progesterone was included primarily as a reference substance. 5α-pregnane-3α-ol-20-one (3αOH-DHP), a potent CNS depressant progesterone metabolite, was included in the in vitro study.

Progesterone: The maternal serum concentration of progesterone is stable during the last three weeks of pregnancy preceding spontaneous labor and through labor. The various modes of delivery studied were elective cesarean section; ocytocin resistant fuctional dystocia; normal, effective, induced labor; and normal, effective, spontaneous labor. The serum progesterone concentrations in dystocia and at elective cesarean section were lower than during normal labor (P<0.005 - p<0.001). Women with ineffectual or no labor at all had progesterone concentrations ranging between 77 and 48% in maternal serum and for umbilical cord serum 65-43% of those at normal labor. In normal labor, primiparous women had higher progesterone concentrations than parous women. When scrutinizing the literature, similar results were found, though interpreted differently. In the in vitro model, human term myometrial muscle strips constantly exposed to progesterone started to contract later (p<0.005), but with a higher frequency (p<0.01) than parallel controls deprived of progesterone. A new property of progesterone emerges when these results are combined with findings in the literature regarding progesterone. Progesterone in high concentrations are related to normal, effective labor.

5α-pregnane-3,20-dione (5αDHP): Mean serum 5αDHP concentrations declined significantly during the last week of pregnancy (p<0.005). During labor, the maternal 5αDHP serum concentration remained stable. No distinct differences according to parity or mode of delivery were evident. The 5αDHP serum concentration in the fetal compartment was double that in the maternal compartment. 5αDHP had only minor effects in the in vitro model. These findings suggest a minor change in 5αDHP production preceding the onset of spontaneous labor, which could contribute to the increased progesterone concentration noted.

5α-pregnane-3α-ol-20-one (3αOH-DHP): No major effects of 3αOH-DHP were seen in the in vitro model. Thus unlikely that it hampers myometrial smooth muscle activity.

In conclusion: Two generally accepted effects of progesterone in relation to parturition are; Decreasing concentrations induce labor while stable or increasing concentrations do have pregnancy maintaining properties. This study suggests a third property of progesterone in relation to human parturition. High and increasing progesterone concentrations seem to have uterotonic properties.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 1991. , 41 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 321
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:umu:diva-46974ISBN: 91-7174-623-4 (print)OAI: oai:DiVA.org:umu-46974DiVA: diva2:441643
Public defence
1991-11-22, Hörsal B (Rosa salen), by 1D, Umeå regionsjukhus, 14:00 (English)
Available from: 2011-09-17 Created: 2011-09-17 Last updated: 2011-09-17Bibliographically approved
List of papers
1. Decrease in serum concentration of 5α-pregnane-3,20-dione prior to spontaneous labor
Open this publication in new window or tab >>Decrease in serum concentration of 5α-pregnane-3,20-dione prior to spontaneous labor
1988 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 67, no 5, 467-470 p.Article in journal (Refereed) Published
Abstract [en]

Serum 5α-pregnane-3,20-dione (5αDHP) and progesterone (P) concentrations before spontaneous labor were studied in 13 women whose pregnancy and delivery were uncomplicated. Blood samples were drawn twice weekly from the 36th week of gestation up to the onset of spontaneous labor. P and 5αDHP values were analysed by applying RIA methods. Mean serum 5αDHP concentrations declined significantly during the last week of pregnancy, from 135±12 nmol/l 5 days prior to spontaneous labor, to 111 ±10 nmol/l on the day spontaneous labor started (p < 0.005). No significant changes in progesterone concentration occurred during the observation period. These results suggest a change in 5aDHP production preceding the onset of spontaneous labor.

Place, publisher, year, edition, pages
wiley online library, 1988
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-46968 (URN)10.3109/00016348809004262 (DOI)3218466 (PubMedID)
Available from: 2011-09-17 Created: 2011-09-17 Last updated: 2017-12-08Bibliographically approved
2. Serum concentrations of progesterone and 5α-pregnane-3,20-dione during labor and early post partum
Open this publication in new window or tab >>Serum concentrations of progesterone and 5α-pregnane-3,20-dione during labor and early post partum
1990 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 69, no 2, 123-126 p.Article in journal (Refereed) Published
Abstract [en]

Serum 5α-pregnane-3,20-dione (5αDHP) and progesterone (P) concentrations were studied in 11 women with uncomplicated pregnancies and deliveries during spontaneous labor and immediately after delivery. Blood samples were drawn 3–6 times during labor, as soon as possible post partum and 1, 3, 6 and 12 h post partum. P and 5αDHP were analysed using RIA methods. There were no significant changes during labor in serum concentration of P and 5αDHP, the values being 366 nmol/l ± 25 SE and 128 nmol/l ±16 SE respectively. Whereas an earlier study has shown a significant decrease in 5αDHP serum concentration between late pregnancy and spontaneous labor, this study showed no decrease during labor, indicating that the decrease occurred before the onset of labor. After parturition, the elimination of P from serum was faster and proportionally greater than for 5αDHR with a half-life of 38 min for P and 58 min for 5αDHP. About 2—3 h post partum the serum concentrations stabilized just above luteal phase values. 12 h post partum, P and 5αDHP were 12% and 23% respectively of pre-partum values.

Read More: http://informahealthcare.com/doi/abs/10.3109/00016349009006156

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-46969 (URN)
Available from: 2011-09-17 Created: 2011-09-17 Last updated: 2017-12-08Bibliographically approved
3. Progesterone concentrations in maternal and fetal serum are lower during functional dystocia than in normal labor
Open this publication in new window or tab >>Progesterone concentrations in maternal and fetal serum are lower during functional dystocia than in normal labor
1992 (English)In: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 79, no 5, 752-759 p.Article in journal (Refereed) Published
Abstract [en]

Concentrations of progesterone and estradiol (E2) were measured in parturient serum and in fetal cord serum during normal labor and in women with functional dystocia. In the study group, there were no cases of cephalopelvic disproportion. In oxytocin-resistant dystocia, the course of labor could not be corrected with oxytocin. To ascertain the effect of oxytocin, we included a number of women whose labor had been induced with oxytocin, followed by normal cervical dilatation and descent of the fetus. All the parturients were grouped retrospectively into those with normal labor and those with dystocia, based on previous definitions. The serum concentrations of progesterone in both the fetal cord and maternal vein were found to be significantly lower in the oxytocin-resistant dystocia group than in women in spontaneous normal labor and those with oxytocin-induced labor and normal progression (P < .05-.005). Oxytocin had no evident effect on the serum concentration of either progesterone or E2, nor did concentrations vary following epidural blockade. Serum E2 concentrations in the maternal vein were similar in all delivery groups. Fetal cord E2 serum concentrations were similar in all vaginal deliveries. Women with the most severe oxytocin-resistant dystocia, delivered by cesarean, had significantly lower serum concentrations of E2 in fetal cord serum compared with the vaginally delivered women (P < .001).

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-46970 (URN)
Available from: 2011-09-17 Created: 2011-09-17 Last updated: 2017-12-08Bibliographically approved
4. High progesterone is related to effective human labor: study of serum progesterone and 5α-pregnane-3,20-dione in normal and abnormal deliveries
Open this publication in new window or tab >>High progesterone is related to effective human labor: study of serum progesterone and 5α-pregnane-3,20-dione in normal and abnormal deliveries
1997 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 76, no 5, 423-430 p.Article in journal (Refereed) Published
Abstract [en]

Background. The role of progesterone levels during human labor is unclear.

Objective. To investigate serum concentrations of progesterone and 5α-pregnane-3,20-dione in normal and abnormal deliveries.

Methods. Venous and umbilical cord serum samples were collected from 108 parturient women. In a further 49 deliveries, arterial and venous umbilical cord sera were collected separately. The concentrations of progesterone and 5opregnane-3,20-dione were determined by radioimmunoassay. The delivery modes studied were: elective cesarean section; oxytocin-resistant dystocia; normal but induced delivery, and normal spontaneous delivery.

Results. Progesterone concentrations in maternal and umbilical serum were higher following normal labor than after dystocia (p<0.005) and elective cesarean section (p<0.005). The maternal and umbilical progesterone concentrations in dystocia and elective cesarean section were between 77–43 % of those in normal labor. The concentrations did not vary between gestational weeks 37 and 42, within the different modes of delivery. The 5α-pregnane-3,20-dione serum concentration in the fetal compartment was twice that in the maternal compartment (p<0.001); its concentration in venous umbilical serum was higher than in corresponding arterial samples (p<0.001). No distinct differences in the 5α-pregnane-3,20-dione serum concentration were found with regard to parity or mode of delivery.

Conclusion. High progesterone concentrations during parturition appear to be related to effective labor. The findings support results from in vitro experiments on human term myometrium.

Read More: http://informahealthcare.com/doi/abs/10.3109/00016349709047823

Keyword
dystocia, labor, 5α-pregnane-3, 20-dione, progesterone
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-46971 (URN)
Available from: 2011-09-17 Created: 2011-09-17 Last updated: 2017-12-08Bibliographically approved
5. Effects in vitro of progesterone and two 5 alpha-reduced progestins, 5 alpha-pregnane-3,20-dione and 5 alpha-pregnane-3 alpha-ol-20-one, on contracting human myometrium at term
Open this publication in new window or tab >>Effects in vitro of progesterone and two 5 alpha-reduced progestins, 5 alpha-pregnane-3,20-dione and 5 alpha-pregnane-3 alpha-ol-20-one, on contracting human myometrium at term
1992 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 71, no 1, 28-33 p.Article in journal (Refereed) Published
Abstract [en]

Progesterone is known to prevent labour at term in domestic animals, but its effect in primates is uncertain. 5 alpha-reduced progesterone metabolites are more potent central nervous system depressants than progesterone is itself. Progesterone and its 5 alpha-reduced metabolites also relax pregnant rat myometrium in vitro. The serum concentration of the initial 5 alpha-reduced metabolite, 5 alpha-pregnane-3,20-dione, is high during pregnancy, but decreases significantly prior to parturition. The next metabolite, 5 alpha-pregnane-3 alpha-ol-20-one, has anaesthetic properties in human beings. The purpose of this study was to ascertain whether these progesterone metabolites also suppress contracting human uterine muscle at term. An in vitro model was devised. Strips of human myometrial muscle were mounted in organ chambers and after regular contractions had become established, the strips were superfused with progestin solutions. The progestins were dissolved in the buffer using an ultrasound bath. Progesterone, used as reference substance, slightly reduced the measured amount of muscular work performed per contraction, recordable after 18 min of exposure (p less than 0.05). Similar results have been reported previously in the literature; 5 alpha-pregnane-3 alpha-ol-20-one showed the same tendency though not significant at the 5% level. 5 alpha-pregnane-3,20-dione evidently reduced the contraction frequency after 10 min of exposure (p less than 0.05). None of the substances affected the duration of the contraction. These 5 alpha-reduced progesterone metabolites are thus not potent inhibitors of contracting human term myometrium in vitro.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-46972 (URN)1315093 (PubMedID)
Available from: 2011-09-17 Created: 2011-09-17 Last updated: 2017-12-08Bibliographically approved
6. Progesterone increases human myometrial contraction frequency, in vitro, if muscle is not deprived of the steroid
Open this publication in new window or tab >>Progesterone increases human myometrial contraction frequency, in vitro, if muscle is not deprived of the steroid
(English)Manuscript (preprint) (Other academic)
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-46973 (URN)
Available from: 2011-09-17 Created: 2011-09-17 Last updated: 2011-09-17Bibliographically approved

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