Development and initial validation of a Swedish inventory to screen for symptoms of deficient perineum in women after vaginal childbirth: 'Karolinska Symptoms After Perineal Tear Inventory'.

BACKGROUND: Perineal tears are common after vaginal birth and may result in pelvic floor symptoms. However, there is no validated questionnaire that addresses long-term symptoms in women with a deficient perineum after vaginal birth. Thus, the objective of this study was to develop and psychometrically evaluate a clinical screening inventory that estimates subjective symptoms in women with a deficient perineum more than one year after vaginal delivery. MATERIAL AND METHODS: The development and psychometric evaluation employed both qualitative and quantitative methods. Qualitative strategies involved content validity and Think Aloud protocol for generation of items. The psychometric evaluation employed principal component analysis to reduce the number of items. The inventory was completed by women with persistent symptoms after perineal tears (N = 170). Results were compared to those of primiparous women giving birth by caesarean section (N = 54) and nulliparous women (N = 338). RESULTS: A preliminary 41-item inventory was developed, and the psychometric evaluation resulted in a final 11-item inventory. Women with confirmed deficient perineum after perineal trauma scored significantly higher on the symptoms inventory than women in control groups. A cut-off value of ≥ 8 could distinguish patients from controls with high sensitivity (100%) and specificity (87-91%). CONCLUSIONS: The Karolinska Symptoms After Perineal Tear Inventory, is a psychometrically valid 11-item patient-reported outcome measure for symptoms of deficient perineum more than one year after vaginal birth. More research is needed to validate the inventory in various patient populations as well as its use in pelvic floor interventions. The inventory has the potential to improve patient counseling and care in the future.

Disposition of serum steroids in response to combined oral contraceptives and menstrual cycle phases: A double-blind, randomized, placebo-controlled study.

To analyze doping control samples from female athletes demands understanding of non-doping factors that affect the steroid profile. These could be physiological factors such as exercise, alcohol consumption, hormonal changes during the menstrual cycle, or the effect of commonly used approved drugs like combined oral contraceptives. Urine samples have been the main way of doping testing, but serum samples are proposed as a complement. Testosterone, dihydrotestosterone, or the ratio of testosterone and androstenedione has been proposed as a biomarker for testosterone doping because it increases after transdermal testosterone administration. In this double-blind, randomized, placebo-controlled study of 340 healthy females, we analyzed the serum steroid levels, including glucuronide metabolites, before and after 3 months of combined oral contraceptives or placebo. At follow up, sample collection in the placebo group was randomly distributed between different menstrual cycle phases. This enabled to analyze changes in concentrations between the follicular, ovulation, and luteal phases. Combined oral contraceptives decreased all serum steroids including the glucuronide metabolites. As expected, serum testosterone levels increased during the ovulation phase, and also androstenedione and androstenediol, whereas the glucuronide metabolites remained unaffected. Neither combined oral contraceptives nor menstrual cycle phases did affect the ratio of testosterone and androstenedione in serum, and consequently this ratio seems promising as a marker of doping with endogenous anabolic androgenic steroids in women.

Klotho Polymorphism in Association With Serum Testosterone and Knee Strength in Women After Testosterone Administration.

Administration of testosterone (T) is associated with increased serum T concentrations and improved physical performance in women. However, the inter-individual variation in T concentrations after T treatment is large and may in part be due to genetic variations. Serum T, as well as dihydrotestosterone (DHT), androstenedione (A) and the T/A ratio have been suggested as promising doping biomarkers for testosterone intake. Here, polymorphisms in androgen metabolic enzyme genes have been investigated in healthy women prior to and after 10 weeks administration of testosterone cream. Klotho is a protein that has been associated with anaerobic strength and here a genetic variation in klotho gene was studied in relation to performance as measured by isokinetic knee strength, as well as to serum androgen disposition. The AKR1C3 genotype (rs12529) was associated with serum T levels at baseline, whereas serum concentrations post T treatment did not differ between genotypes. The SLCO2B1 (rs12422149) and UGT2B17 deletion polymorphisms were not associated with serum concentration of either T, DHT or A. The klotho polymorphism (rs9536314) was associated with serum concentrations of both total T and T/A ratio after T administration. Individuals with the GT genotype increased T concentrations and T/A ratio more than women homozygous for the T allele. No significant difference in the association of klotho genotype with knee muscle strength was observed between placebo and T treatment. However, individuals homozygous for the T allele showed higher isometric mean torque scores at exit than GT subjects after T administration. This is the first time a genotype has been associated with androgen concentrations after T administration and muscle strength in women. Our results imply that subjects with a polymorphism in klotho may be more prone to detection using serum T and A as biomarkers.

Impact of hormonal contraceptives on urinary steroid profile in relation to serum hormone changes and CYP17A1 polymorphism.

To detect doping with endogenous steroids, six urinary steroids are longitudinally monitored in the athlete biological passport (ABP). These steroids include testosterone, etiocholanolone, androsterone, 5α-androstane-3α,17ß-diol, 5ß-androstane-3α,17ß-diol, and the testosterone isomer epitestosterone. It is known that the intake of hormonal contraceptives may interfere with the ABP biomarkers. A previous study showed that athletes using hormonal contraceptives (HCs) display lower urinary epitestosterone concentrations than non-using athletes. In this study, we analyzed the urinary steroid profile prior to and three months after administration of an oral HC including levonorgestrel and ethinylestradiol (n = 55). The urinary concentrations of all the ABP metabolites decreased after three months, with epitestosterone showing the largest decline (median 6.78 to 3.04 ng/mL, p˂0.0001) followed by 5α-androstane-3α,17ß-diol (median 23.5 to 12.83 ng/mL, p˂0.0001), and testosterone (median 5.32 to 3.66, p˂0.0001). Epitestosterone is included in two of the five ratios in the ABP (T/E and 5αAdiol/E), and consequently these ratios increased 1.7-fold (range 0.27 to 8.50) and 1.26-fold (range 0.14 to 5.91), respectively. Some of these changes may mimic the changes seen after administration of endogenous steroids leading to atypical findings. Notably, even though participants used the same contraceptive treatment schedule, the HC-mediated epitestosterone change varied to a large extent (median 0.43-fold, range 0.06 to 6.5) and were associated with a functional T˃C promoter polymorphism in CYP17A1. Moreover, the epitestosterone changes correlated with HC-induced testosterone and gonadotropins changes in serum, indicating that urinary epitestosterone reflects the androgen load in HC-using women.