Classification, comorbidity, heredity, and risk factors of female sexual dysfunctions

Female sexual dysfunctions, including desire, arousal, orgasm and pain problems, have been shown to be highly prevalent among women around the world. The etiology of these dysfunctions is unclear but associations with health, age, psychological problems, and relationship factors have been identified. Genetic effects explain individual variation in orgasm function to some extent but until now quantitative behavior genetic analyses have not been applied to other sexual functions. In addition, behavior genetics can be applied to exploring the cause of any observed comorbidity between the dysfunctions. Discovering more about the etiology of the dysfunctions may further improve the classification systems which are currently under intense debate. The aims of the present thesis were to evaluate the psychometric properties of a Finnish-language version of a commonly used questionnaire for measuring female sexual function, the Female Sexual Function Index (FSFI), in order to investigate prevalence, comorbidity, and classification, and to explore the balance of genetic and environmental factors in the etiology as well as the associations of a number of biopsychosocial factors with female sexual functions. Female sexual functions were studied through survey methods in a population based sample of Finnish twins and their female siblings. There were two waves of data collection. The first data collection targeted 5,000 female twins aged 33–43 years and the second 7,680 female twins aged 18–33 and their over 18–year-old female siblings (n = 3,983). There was no overlap between the data collections. The combined overall response rate for both data collections was 53% (n = 8,868), with a better response rate in the second (57%) compared to the first (45%). In order to measure female sexual function, the FSFI was used. It includes 19 items which measure female sexual function during the previous four weeks in six subdomains; desire, subjective arousal, lubrication, orgasm, sexual satisfaction, and pain. In line with earlier research in clinical populations, a six factor solution of the Finnish-language version of the FSFI received supported. The internal consistencies of the scales were good to excellent. Some questions about how to avoid overestimating the prevalence of extreme dysfunctions due to women being allocated the score of zero if they had had no sexual activity during the preceding four weeks were raised. The prevalence of female sexual dysfunctions per se ranged from 11% for lubrication dysfunction to 55% for desire dysfunction. The prevalence rates for sexual dysfunction with concomitant sexual distress, in other words, sexual disorders were notably lower ranging from 7% for lubrication disorder to 23% for desire disorder. The comorbidity between the dysfunctions was substantial most notably between arousal and lubrication dysfunction even if these two dysfunctions showed distinct patterns of associations with the other dysfunctions. Genetic influences on individual variation in the six subdomains of FSFI were modest but significant ranging from 3–11% for additive genetic effects and 5–18% for nonadditive genetic effects. The rest of the variation in sexual functions was explained by nonshared environmental influences. A correlated factor model, including additive and nonadditive genetic effects and nonshared environmental effects had the best fit. All in all, every correlation between the genetic factors was significant except between lubrication and pain. All correlations between the nonshared environment factors were significant showing that there is a substantial overlap in genetic and nonshared environmental influences between the dysfunctions. In general, psychological problems, poor satisfaction with the relationship, sexual distress, and poor partner compatibility were associated with more sexual dysfunctions. Age was confounded with relationship length but had over and above relationship length a negative effect on desire and sexual satisfaction and a positive effect on orgasm and pain functions. Alcohol consumption in general was associated with better desire, arousal, lubrication, and orgasm function. Women pregnant with their first child had fewer pain problems than nulliparous nonpregnant women. Multiparous pregnant women had more orgasm problems compared to multiparous nonpregnant women. Having children was associated with less orgasm and pain problems. The conclusions were that desire, subjective arousal, lubrication, orgasm, sexual satisfaction, and pain are separate entities that have distinct associations with a number of different biopsychosocial factors. However, there is also considerable comorbidity between the dysfunctions which are explained by overlap in additive genetic, nonadditive genetic and nonshared environmental influences. Sexual dysfunctions are highly prevalent and are not always associated with sexual distress and this relationship might be moderated by a good relationship and compatibility with partner. Regarding classification, the results supports separate diagnoses for subjective arousal and genital arousal as well as the inclusion of pain under sexual dysfunctions.

Molecular Mechanisms of Sexual Dimorphism in Threespine Stickleback

Sexual dimorphism is commonly understood as differences in external features, such as morphological features or coloration. However, it can more broadly encompass behavior and physiology and at the core of these differences is the genetic mechanism – mRNA and protein expression. How, and which, molecular mechanisms influence sexually dimorphic features is not well understood thus far. DNA, RNA and proteins are the template required to create the phenotype of an individual, and they are connected to each other via processes of transcription and translation. As the genome of males and females are almost identical with the exception of the few genes on the sex chromosome or the sex-determining alleles (in the case of organisms without sex chromosomes), it is likely that many of the downstream processes resulting in sexual dimorphism are produced by changes in gene regulation and result from a regulatory cascade and not from a vastly different gene composition. Thus, in this thesis a systems biology approach is used to understand sexual dimorphism at all molecular levels and how different genomic features, e.g. sex chromosome evolution, can affect the interplay of these molecules. The threespine stickleback, Gasterosteus aculeatus, is used as the model to investigate molecular mechanisms of sexual dimorphism. It has well-characterized ecology and behavior, especially in the breeding season when sexual dimorphism is high. Moreover, threespine stickleback has a recently evolved Y chromosome in the early stages of sex chromosome evolution, characterized by a lack of recombination leading to degeneration (i.e. gene loss). The aim of my thesis is to investigate how the genotype links to the molecular phenotype and relates to differences in molecular expression between males and females. Based on previous research on sex differences in mRNA expression, I investigated sex-biased protein expression in adult fish outside the breeding season to see if differences persisted after translation. As sex-biased expression also prevailed in the proteome and previous transcription expression seemed to be related to the sex chromosomes, I investigated the genome level with a particular focus on the sex-chromosomes. I characterized the status of Y chromosome degeneration in the threespine stickleback and its effects on gene function. Furthermore, since the degeneration process leaves genes in a single copy in males, I examined whether the resulting dosage difference of messenger RNA for hemizygous genes is compensated as it is in other organisms. In addition, threespine sticklebacks have wellcharacterized behavioral differences related to the male’s social status during the breeding season. To understand the connection between the genotype and behavior, I examined gene expression patterns related to breeding behavior using dominant and subordinate males as well as female