Skip to content

Paper: Coital Role Discordance

Congenital Copulatory Role Discordance : A Novel Difference of Sex Development

Abstract

// The abstract will be written last after the rest v.s. wasting time polishing it now, below is a draft abstract

Congenital Copulatory Role Discordance (CRD) is a proposed Differences of Sex Development (DSD) where an individual's genetically predisposed copulatory role preference (insertive or receptive) mismatches their physical sex characteristics. Distinct from gender identity and sexual orientation, CRD focuses on the biological preference for insertive or receptive roles during intercourse. We present how CRD can arise from developmental and activation variations in steroidogenesis affecting the Ventrolateral-Ventromedial Nucleus of the Hypothalamus (VL-VMH), specifically the ratio of Aromatase, Estrogen Receptor Alpha/Beta, and Progesterone Receptor. This paper defines CRD, explores its genetic/hormonal basis, and analyzes existing DSD and gender/sexual identity data for preliminary evidence of CRD. Understanding CRD has implications for our understanding of sexual differentiation and clinical practice.

Introduction

While the development of gonads and external genitalia serves as an observable marker of sex, a less visible, yet equally crucial, aspect of sex resides within the brain shaping reproductive behavior. This paper introduces the concept of "Congenital Copulatory Role Discordance," a proposed Differences of Sex Development (DSD), condition wherein a disconnect arises between an individual's genetically determined preferred copulatory role (insertive or receptive) and their external physical sex characteristics. Similar to other DSD’s, such as Complete Androgen Insensitivity Syndrome (CAIS) or Turner Syndrome, this DSD is not readily visible at birth, but is a 46,XX chromosomes with virilization or 46,XY chromosomes with undervirilization DSD. While there are reports and discussions of Congenital Copulatory Role Discordance, it currently does not have a name or precise definition.

Copulatory role preference, as used here, refers to an individual's preference for the insertive or receptive role during penile-vaginal intercourse. The terms "insertive" and "receptive" are used here to describe these biologically defined copulatory roles. Biologically, "insertive" refers to the role typically associated with the individual possessing a penis, while "receptive" refers to the role typically associated with the individual possessing a vagina. This definition is intentionally narrow and does not encompass other sexual activities or preferences. While it is acknowledged that other terms, such as "top" and "bottom," are used in some communities to describe sexual roles, this discussion will adhere to the more specific and biologically defined terms "insertive" and "receptive" to avoid ambiguity.

Congenital Copulatory Role Discordance occurs when there is a misalignment between the expected copulatory role associated with an individual's genitalia and their actual neural organization and behavioral predispositions. This discordance can potentially manifest in a variety of ways, including, but not limited to, atypical sexual preferences and a discordance between assigned sex and gender identity.

Sexual behavior is a complex process involving numerous brain regions and neural circuits. While the exact mechanisms are still being investigated, copulatory role preference has been shown to be developed by the activation or lack of activation of estrogen receptor alpha (ERα) during the perinatal period. Genetic variants leading to atypical estrogen levels during this time would result in atypical outcomes. Further genetic variants can also result in atypical hormone levels and activation of the resulting neural architecture during adult years.

This paper aims to define Congenital Copulatory Role Discordance as a distinct DSD, investigate the genetic mechanisms through which variations in steroidogenesis can disrupt the development and activation of the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the Ventromedial nucleus of the hypothalamus (VL-VMH), and identify other commonly associated conditions that can be used for diagnostic criteria. Further we will analyze existing data from individuals with DSDs and those expressing discordance between assigned sex and gender identity to provide evidence for the existence of this proposed condition.

Defining Congenital Copulatory Role Discordance

Congenital Copulatory Role Discordance (CRD) is defined as a Difference of Sex Development (DSD) characterized by a significant and persistent incongruence between an individual's genetically predisposed preference for a specific copulatory role (insertive or receptive) during penile-vaginal intercourse and their external physical sex characteristics. This preference, refers to the innate biological predisposition for either the insertive or receptive role. It is distinct from sexual orientation and gender identity, although it may interact with both.

The diagnostic criteria for CRD include:

  1. Consistent Discordance: Evidence of a consistent and strong preference for a copulatory role that is discordant with the expected role based on the individual's external genitalia. This preference must be more than a fleeting interest or experimentation.
  2. Developmental History: Consideration of the individual's developmental history, including any known genetic or hormonal variations that could influence CRD.
  3. Co-occurring conditions: Due to the underlying mechanisms, other disorders frequently will occur alongside CRD.
  4. Exclusion of Sociocultural Factors: A lack of clear explanation for the discordant preference based on social, cultural, or psychological factors alone. While these factors may influence expression, they are not considered the primary drivers of CRD.
  5. Exclusion of Epigenetic Influences: A lack of evidence for epigenetic influences on hormonal levels or gene expression that could otherwise explain the observed CRD.

It is important to acknowledge that diagnosing CRD may present challenges, as copulatory role preference is not always readily expressed or easily assessed. Further research is needed to develop standardized assessment tools and refine diagnostic criteria. Furthermore, self-identification may be the most accurate way to assess CRD.

Distinguishing CRD from Other Sexual Variations

  • Gender Identity: While CRD may co-occur with a discordance between assigned sex and gender identity, they are distinct constructs. An individual may identify with their assigned sex but still experience CRD.
  • Sexual Orientation: CRD is distinct from sexual orientation, which describes attraction (e.g., same-sex, opposite-sex, both, etc). CRD focuses on the preference for insertive or receptive roles during penile-vaginal intercourse, regardless of partner sex. Individuals of any sexual orientation may experience CRD.
  • Other DSDs: CRD focuses on the neural organization underlying copulatory role preference. While some individuals with other DSDs may also experience CRD, the two are not synonymous.
  • Paraphilias: CRD is not a paraphilia. Paraphilias involve unusual sexual interests/behaviors causing distress or impairment. CRD, as defined, does not inherently imply distress or dysfunction.

Prevalence and Demographics

At this stage, the prevalence of CRD is unknown. Due to the novelty of the formalization and the lack of standardized assessment tools, epidemiological data is not yet available. Future research will be crucial to determine the prevalence of CRD in different populations and to explore any potential demographic patterns or trends. It is anticipated that CRD will be uncommon, as it requires specific genetic variations that result in specific hormone level variations at specific times of development. It is also anticipated that CRD will be more common in individuals with other DSDs.

II. Neurobiological Basis of Copulatory Role Preference

  • Detail the current understanding of how the brain develops and becomes sexually differentiated concerning mating behaviors.
  • Discuss key brain regions, hormones, and neural circuits involved in these behaviors.
  • Explain how these neural circuits might be influenced by both genetic and environmental factors.

Emphasize the potential for independent development of these neural circuits separate from other aspects of sexual differentiation.

Neurobiological Basis of Copulatory Role Preference

// Talk about everything relevant to what is in the sections that follow

//

Abundant evidence suggests that the presence or absence of estradiol (E2) during development rather than the direct effects of sex chromosomes exerts profound and irreversible effects in the brain to specify the adult mating behavior. https://doi.org/10.1016/j.yfrne.2005.06.001 It is important to recognize that the E2 levels can result in a spectrum and not simply two binary output configurations.

In males, around the time of birth Luteinizing Hormone (LH) rises, causing androgen to be produced in the gonads, which can then be converted by aromatase to estradiol (E2). This results in male behavior in adulthood. Females that lack this E2 activation result in female copulatory role preference.

In contrast Females treated early in life with testosterone or its aromatized metabolite estradiol (E2) which activated ERα behaved like males and neonatally castrated males or males with a knockout ERα behaved like females. https://doi.org/10.1210/endo-65-3-369 https://doi.org/10.1006/hbeh.1997.1419

Sexually dimorphic nucleus of the preoptic area

The third interstitial nucleus of the anterior hypothalamus (INAH3) (also known as the sexually dimorphic nucleus of the preoptic area (SDN-POA) in mammals) determines male mating role behavior.

Females treated with E2 during the critical prenatal period developed equivalent in size to that of normal males. https://doi.org/10.1016/0006-8993(84)90242-7, https://doi.org/10.1210/en.2007-0454 The INAH3 exposed to E2 results in higher levels of Aromatase expression.

Ventromedial nucleus of the hypothalamus (VMH)

The ventromedial nucleus of the hypothalamus (VMH) primarily focused on sexual role behavior in females and not male role behavior.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8331052/

High levels of receptivity can be elicited only following the combined action of estrogen and progesterone.
https://doi.org/10.1016/0031-9384(70)90167-8

Males exhibit higher levels of both the androgen receptor and aromatase, than females in the VL-VMH. Conversely, females manifest more ER-α, ER-β and PR receptors than males.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3085563/

III. Genetic Mechanisms of Congenital Copulatory Role Discordance:

  • Propose specific genetic pathways that could lead to a dissociation between copulatory role determination and genital development.
  • Discuss potential candidate genes involved in brain development, hormone signaling, and sex differentiation pathways.
  • Explore possible genetic variations (e.g., mutations, polymorphisms, epigenetic modifications) that could disrupt the typical alignment of copulatory role and physical sex characteristics.
  • Consider the role of sex chromosomes (e.g., X, Y) and how variations (e.g., XXY, X0) might contribute.
  • Address the concept of dosage compensation and its potential role.
  • Discuss the possibility of gene expression differences in specific brain regions related to copulatory behavior.

Mechanisms of Congenital Copulatory Role Discordance

A female copulatory role when there is a working SRY gene (XY case).

// walk through the various steps showing how they could be broken.

Preventing masculinization during the perinatal period

  1. Something that reduces the LH, followed by T raise

Or a number of things that will each lower SHBG

Hypothyroidism
https://pubmed.ncbi.nlm.nih.gov/15142373/

Thyroid hormone deficiency lowers SHBG
https://jme.bioscientifica.com/view/journals/jme/43/1/19.xml#:~:text=Thyroid%20hormones%20(triiodothyronine%20(T3,HNF%2D4%CE%B1%20levels%20in%20hepatocytes.

As seen in trans women
Hypothyroidism is more common in the transgender community than in the general population:

Vitamin D lowers SHGB
https://www.tandfonline.com/doi/full/10.3109/13685538.2015.1034686

As seen in trans women

Insulin resistance lowers SHBG
https://academic.oup.com/jcem/article-abstract/99/12/E2780/2833758?redirectedFrom=fulltext\&login=false

  1. Poor Estrogen signaling

Genetic Link Between Gender Dysphoria and Sex Hormone Signaling | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic

Aromatase deficiency
ESR1
COMT
SUT

  1. Genetic variants in the setup of INAH3 or VMH outside the control of ERa activation

…

  1. Hormone activation as an adult

SDN-POA reduction:
AR with a long promoter
10.1016/j.biopsych.2008.08.033

Not CYP19 - aromatase

VMH:
21-Hydroxylase deficiency, 11B- deficiency to produce progesterone to finalize the

A male copulatory role when there is no SRY gene (XX case).

  1. Something that results in estrogen production during the perinatal period

CAH
17α-hydroxylase excess
strong estrogen signaling

CYP19A1 - nothing
https://academic.oup.com/jsm/article-abstract/11/3/720/6958023?redirectedFrom=fulltext
Something rs74357
https://www.sciencedirect.com/science/article/pii/S0015028207012289

Longer promoter of ERb
https://academic.oup.com/jsm/article-abstract/11/3/720/6958023?redirectedFrom=fulltext

Trans men long ERa promoter, but 799
https://academic.oup.com/jsm/article-abstract/14/3/464/6973433?redirectedFrom=fulltext

  1. Hormone activation as an adult

SDN-POA:
CAH provides the androgen

Epigenetic:
Smoking

IV. Evidence for Congenital Copulatory Role Discordance from Existing Research:

  • Review existing literature on intersex variations, focusing on cases where there might be a Discordance between assigned sex and behavioral/psychological sex characteristics.
  • Analyze genetic studies of individuals with intersex conditions, looking for evidence of the genetic variations proposed in Section III.
  • Critically examine studies of individuals undergoing Sex Reassignment Surgery (SRS) for gender dysphoria. Focus on genetic data (if available) to see if it supports the presence of genetic markers associated with the opposite copulatory role.
  • Discuss any behavioral or psychological studies that might provide indirect evidence for the concept of Congenital Copulatory Role Discordance in these populations.
  • Address limitations of existing studies and suggest future research directions.

Congenital Copulatory Role Discordance Comorbidities

Because there can be many different causes a valuable thing to evaluate the sum

Poor estrogen signaling is known to cause the following

  • Hypospadias

Evidence for Congenital Copulatory Role Discordance from Existing Research

Those who would want to undergo SRS to have sex the way that they preferred is an excellent place to start looking. There is a lot of research around intersex or transgender folks researching their genetics. Congenital Copulatory Role Discordance isn’t gender identity, but the groups overlap.

Transwomen with longer AR promoters

Trans women with shorter PR promoters

Reverse cases

Other researchers have studied correlations between INAH-3 volume and other aspects of sexual
identity. A study of transgender individuals by neuroanatomist Dick Swaab found male-to-female transgender people to have a size and number of neurons of INAH-3 closer to a normal female range, and that female-to-male transgender people have a size and number of INAH-3 neurons closer to a normal male range. This finding that the size of the INAH-3 more closely corresponded to the gender the subject identified with rather than their biological or chromosomal gender has since been repeated, but is still controversial due to potential confounds of hormone replacement therapy.[17][18]
https://doi.org/10.1093/brain/awn276

V. Discussion:

  • Summarize the key findings and reiterate the definition of Congenital Copulatory Role Discordance.
  • Discuss the implications of this concept for understanding sex and gender identity.
  • Acknowledge any limitations of the proposed theory or the evidence presented.
  • Address potential criticisms or counterarguments.
  • Propose future research directions, including specific genetic studies, neuroimaging studies, and behavioral studies.
  • Discuss the broader societal implications of recognizing Congenital Copulatory Role Discordance.
  • Ethics: Discuss the ethical implications of researching Congenital Copulatory Role Discordance. Ensure your research design respects the privacy and autonomy of individuals with intersex variations or gender dysphoria.

Discussion

Possible two common sub groupings of CRD in AMAB and associated conditions/treatments?

Estrogen insensitivity syndrome (aka ESR1) symptoms?

  • More likely to identify as a lesbian post-hrt?
  • Need progesterone supplement for breast development (and libido?)
  • Low vitamin d, MCAS pre-hrt
  • Might want to try alternative forms of estrogen than estradiol for possible better ESR1 binding to their variant

Poor estrogen signaling due to low LH, low SHBG & NCAH etc

  • More likely to identity as straight post-hrt?
  • Less likely to need progesterone?

VI. Conclusion:

  • Concisely restate the significance of the Congenital Copulatory Role Discordance concept.
  • Emphasize the need for further research to validate and refine the theory.
  • Offer a final thought-provoking statement about the complexity of sex and the importance of understanding its diverse manifestations.

VII. References:

  • Include a comprehensive list of all cited sources.

// https://old.reddit.com/r/asktransgender/comments/154t1qq/my_master_list_of_trans_health_citations_2nd_draft/