Brigitte Leeners

Prolactin secretion patterns: basic mechanisms and clinical implications for reproduction

Prolactin (PRL) is one of the most versatile hormones in the mammalian body affecting reproductive, sexual, metabolic, immune, and other functions. It is therefore not surprising that the neural control of PRL secretion is complex, involving the coordinated actions of several hypothalamic nuclei. A plethora of experimental data exists on the hypothalamic control of hormone secretion under various physiological stimuli. There have been even mathematical models and computer studies published, which help to understand the complex hypothalamic-pituitary network. Nevertheless, the putative role of PRL for human reproduction still has to be clarified. Here, we review data on the underlying mechanisms controlling PRL secretion using both experimental and mathematical approaches. These investigations primarily focus on rhythmic secretion in rats during early pregnancy or pseudopregnancy, and they point to the important role of oxytocin as a crucial PRL-releasing factor. Recent data on human studies and their theoretical and clinical implications are reviewed as well. In particular, studies demonstrating a sustained PRL surge after sexual climax in males and females are presented, indicating possible implications for both sexual satiation and reproductive functions. Taking these data together, there is evidence for the hypothesis that the PRL surge induced by sexual activity, together with the altered PRL rhythmic pattern, is important for successful initialization of pregnancy not only in rodents but also possibly in humans. However, further investigations are needed to clarify such a role in humans.

Pregnancy complications in women with childhood sexual abuse experiences

OBJECTIVE Childhood sexual abuse (CSA) has an estimated prevalence of 20% and has a constantly growing list of known long-term consequences on physical as well as psychological health which may also influence obstetrical care attributed to it. However, scientific data on the association of CSA and pregnancy are sparse. Therefore, the study investigated pregnancy complications in women exposed to CSA. METHODS The study was designed as a cohort study comparing 85 women exposed to CSA with 170 matched unexposed women. CSA was identified by interview using modified questions from Wyatt [Child Abuse Negl 9 (1985) 507-519]. Data on pregnancy complications were collected by questionnaire and based on entries in a booklet (Mutterpass) in which all relevant data on pregnancy are documented at each prenatal consultation for any women attending prenatal care in Germany. Statistical analysis was performed with chi square, Fishers Exact Test, and multiple logistic regression analysis to control the association between CSA and pregnancy complications for confounders significant in univariate analysis, i.e., physical abuse, other adverse experiences during childhood, abuse during pregnancy, substance abuse, and occupation. RESULTS Women exposed to CSA were significantly more often hospitalized during pregnancy (41.2%/19.4%; OR 2.91, CI 1.64-5.17). They presented more often complications such as premature contractions (38.8%/20%; OR 2.54 CI 1.43-4.51), cervical insufficiency (25.9%/9.4%; OR 3.36, CI 1.65-6.82), and premature birth (18.8%/8.2%; OR 2.58, CI 1.19-5.59). CONCLUSION Therefore, health care providers should adapt prenatal care to the specific needs of women exposed to CSA.

BMI : new aspects of a classical risk factor for hypertensive disorders in pregnancy

HDP (hypertensive diseases in pregnancy) are one of the leading causes of maternal and fetal mortality and morbidity. BMI (body mass index) is an established risk factor for pre-eclampsia, but its role in HELLP syndrome is unknown. We therefore investigated BMI as a risk factor in the development of HELLP syndrome. At the beginning of pregnancy, BMI was measured in 1067 women with a history of HDP and 1063 controls. Diagnoses of HDP were classified according to ISSHP (International Society for the Study of Hypertension in Pregnancy) and BMI according to WHO (World Health Organization) criteria. After verification of exclusion criteria and matching for confounders, 687 women with hypertensive diseases in pregnancy and 601 controls remained for statistical evaluation by chi(2) test and multiple logistic regressions. As a continuous variable, the increase in BMI was associated with an increase in the development of gestational hypertension {OR (odds ratio), 1.1 [95% CI (confidence interval) 1.062-1.197]} and pre-eclampsia [OR, 1.1 (95% CI, 1.055-1.144)]}, but not for HELLP syndrome. According to WHO definitions, overweight women (BMI > or =25 and <30 kg/m(2)) had a 2-fold (95% CI, 1.365-2.983) risk and obese women (BMI > or =30 kg/m(2)) had a 3.2-fold (95% CI, 1.7-5.909) risk of developing pre-eclampsia when compared with women of normal weight (BMI > or =15.5 and <25 kg/m(2)). Being overweight or having obesity had no effect on the risk of HELLP syndrome. As an increased BMI is correlated with the risk of developing pre-eclampsia but not HELLP syndrome, both diseases have a different risk profile. This finding supports that underlying physiological mechanisms in pre-eclampsia vary from those in HELLP syndrome.

Emotional stress and the risk to develop hypertensive diseases in pregnancy.

Objective: Cardiovascular diseases are strongly influenced by stress and do share several risk factors with hypertensive diseases in pregnancy (HDP). The aim of the study is to investigate the correlation between emotional stress during pregnancy and the risk for HDP. Methods: A self-administered questionnaire comprising obstetrical and psychosocial questions was completed by 725 patients and 880 controls matched for age, parity, nationality, and educational level. Results: Emotional stress during pregnancy was associated with a 1.6-fold increased risk for HDP. Conclusion: Psychosocial interventions to reduce emotional stress during pregnancy may help to decrease the risk to develop HDP.

Risk factors for unfavorable pregnancy outcome in women with adverse childhood experiences

Abstract Aims: To explore the association between childhood sexual abuse (CSA), physical abuse, as well as other adverse childhood experiences (ACE), and different obstetrical risk factors/behaviors. Methods: In this cohort study, obstetrical risk factors and perinatal outcome in 85 women exposed to CSA were compared to 170 matched unexposed women. CSA, physical abuse, and ACE were explored by face-to-face interviews and by questionnaire. Data on perinatal outcome were extracted from medical charts. Fisher’s exact, χ2-test, and multiple logistic regression were used for statistical analysis. Results: During pregnancy women with CSA experiences were significantly more often smoking (31.7%/9.4%; P<0.0001), had partners abusing drugs (10.6%/1.2%; P<0.0005), experienced physical (16.5%/0; P<0.0001), sexual (12.9%/0; P<0.0001), and emotional abuse (44.7%/1.7%; P<0.0001), reported depression (24.7%/1.8%; P<0.0001), and suicidal ideation (10.6%/0; P<0.0001) than women without CSA experiences. Differences in risk factors were more often correlated with physical than with sexual abuse during childhood. The probability for premature delivery was associated with CSA, physical abuse and ACE as well as with several of the risk factors investigated. Conclusion: Women with CSA, physical, and ACE present with a variety of abuse-associated obstetrical risk factors and an increased risk for premature delivery. Therefore, all types of abusive and other ACE should be considered in prenatal care.

Breast-feeding in women with hypertensive disorders in pregnancy.

Abstract Aims: Breast feeding is particularly important and difficult in children born prematurely, especially after hypertensive diseases in pregnancies (HDP). Therefore, we aimed to investigate breast feeding in women who developed HDP. Methods: Data on breast-feeding was collected within a nationwide research project on psychosocial factors in HDP. A self-administered questionnaire was given to 2600 women with a suspected history of HDP and 1233 controls. After matching and confirming diagnosis according to ISSHP criteria, 877 women with HDP and 623 controls were included into the study. Results: Control women initiated (48.9/39.2%; P<0.001) and continued (42.2/37.2%; P<0.005) breast-feeding significantly more often than women with HDP. This holds particularly for women who developed HELLP syndrome (48.9/34.7%; P<0.0001, 42.2/33.5%; P<0.0001). A delivery before the 32nd gestational week (19.5/81.8%; P<0.0001) and a birth weight of less than 1500 g (18.8/75%; P<0.0001) were associated with the decision not to breast-feed. Conclusions: Women affected by HDP breast fed significantly less often than control women. This effect is at least partly caused by the increased rate of prematurity. Encouraging and supporting these women in breast-feeding is important to improve neonatal physical and mental development.

Prolactin secretory rhythm in women: immediate and long-term alterations after sexual contact

BACKGROUND Prolactin (PRL) is one of the most versatile hormones in the mammalian body, affecting reproductive, sexual and other functions. In rats, mating or vaginocervical stimulation activates a characteristic PRL secretory pattern for several days, which is essential for successful reproduction. Although the underlying mechanisms appear to be different, PRL is also crucial for human fertility. We have detected a PRL increase in women induced by sexual intercourse. Extending these findings, the current study aimed at analyzing the PRL secretory rhythm after sexual contact, in order to elucidate whether human females also show long-term alterations of the PRL secretory pattern. METHODS In a pilot study, serial blood samples were taken from women (n= 7) in mid-cycle to assess changes in PRL secretory rhythm induced by sexual intercourse, during a period of 32 h. RESULTS Compared with control condition, sexual intercourse with orgasm induced not only the well-established immediate PRL increase of ~300% but also an additional PRL elevation around noon of the next day (P< 0.05). These fluctuations were measured on top of the regular circadian rhythm of PRL, manifested as a surge early in the morning. CONCLUSIONS We are able to demonstrate a long-term change in the PRL secretory rhythm after sexual intercourse with orgasm in females, suggesting memory effects. We hypothesize that the additionally secreted PRL could be beneficial for decidualization and implantation. Further studies with more participants are required to investigate in detail the implications of such effects on reproductive success in humans.

The Quality of Sexual Experience in Women Correlates with Post‐Orgasmic Prolactin Surges: Results from an Experimental Prototype Study

INTRODUCTION Sexual intercourse, orgasm, and sexual satisfaction are associated with well-being and improved quality of life. The pituitary hormone prolactin (PRL) may have an important role in regulating (and thus indexing) sexual satiety and satisfaction. AIM Physiological indices to quantify the quality and resulting satisfaction from female orgasm would be valuable. Therefore we aim to validate associations of orgasm-induced PRL surges with womens orgasm quality and subsequent sexual satisfaction. METHODS In a prospective study, with a pre-post, single-blinded, cross-over design in a naturalistic field setting, we analyzed the correlation of womens post-orgasmic serum PRL surges following sexual intercourse with womens perceived quality of orgasm and resulting sexual satisfaction, as measured by a questionnaire. MAIN OUTCOME MEASURES PRL levels prior to and following penile-vaginal intercourse with and without orgasm, and scores from the Acute Sexual Experience Scale (ASES) on quality of orgasm and sexual satisfaction. RESULTS An analysis of variance of the blood samples in nine women indicated large magnitude, significant effects of intercourse orgasm on PRL levels (P = 0.004, eta squared = 0.78), as well as an interaction with the effect of multiple orgasms (P = 0.008, eta squared = 0.80). PRL post/pre ratios and arithmetic difference correlated strongly with orgasm quality (r = 0.85, P = 0.016, and r = 0.69, P = 0.08) and sexual satisfaction (r = 0.75, P = 0.05 and r = 0.77, P = 0.045). CONCLUSION Womens intercourse orgasm induced PRL surges are strongly related to the quality of orgasm and subsequent sexual satisfaction. This implies that post-orgasmic PRL surges are an objective index of orgasm and orgasm quality. PRL might be used in future studies on basic research as well as a treatment target in sexual disorders in women.

Neither maternal nor fetal mutation (E474Q) in the α-subunit of the trifunctional protein is frequent in pregnancies complicated by HELLP syndrome

Abstract Objective: An association between maternal HELLP syndrome and fetal long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has been proposed. LCHAD catalyzes the third step in the β-oxidation of fatty acids in mitochondria. Whereas about 75% of LCHAD-deficient patients carry a G-to-C mutation at nucleotide position 1528 (Glu474Gln, E474Q) on both chromosomes, compound heterozygosity for E474Q on one chromosome and a second different LCHAD mutation on the other can be observed in up to 25% of LCHAD-deficiency cases; only very few patients carry two mutations different from E474Q. Genetic analysis of the mother alone is insufficient in case of compound heterozygosity. Since information on the fetal carrier status of the E474Q mutation in maternal HELLP syndrome is rare, we investigated the frequency of the E474Q mutation in families where the mother had HELLP syndrome. Methods: The occurrence of the E474Q mutation was analyzed by PCR and RFLP in 103 mothers with HELLP syndrome, in 82 children of affected pregnancies and in 21 fathers in families where fetal DNA was not available. In addition, 103 control women with only uncomplicated pregnancies were investigated. Results: The mutation E474Q was not detected in the study population. Conclusion: Neither maternal nor fetal heterozygosity for the E474Q mutation is a relevant factor of HELLP syndrome.

Colour Doppler sonography improves the pre-operative diagnosis of ovarian tumours made using conventional transvaginal sonography

OBJECTIVE Conventional transvaginal ultrasound-and transvaginal colour Doppler flow were used to assess morphology and circulation of pelvic masses. STUDY DESIGN One hundred and nine adnexal masses in 101 women were examined between January 1993 and September 1994. Morphology was classified after a score published by Sassone et al. in 1991. Doppler waveforms using the lowest resistance index (RI), the pulsatility index (PI) and peak flow velocity were used for analysis. Ninety five patients underwent laparotomy. Following histopathological evaluation best cut-off values, sensitivity and specificity were calculated. Score results were compared with Doppler results and a combination of both methods. RESULTS A combination of Doppler sonography and conventional transvaginal sonography led to a sensitivity of 74.0% and a specificity of 73.7%. Eight out of 15 malignant masses were classified as stage I. An analysis of the false positive diagnoses showed that important information can be gained when Doppler sonography is performed. In particular, on solid appearing adnexal masses, Doppler sonography leads to a high accuracy (84.6%). CONCLUSION Colour Doppler sonography is not applicable in routine clinical practice, but can give important additional information in specific cases. For solid appearing masses and in early ovarian malignancy, Doppler sonography facilitates the preoperative discrimination between benign and malignant processes.