\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Pelvic pain in transgender people using testosterone therapy: A national
survey}



\author[1]{Sav Zwickl}%
\author[1]{Laura Burchill}%
\author[1]{Alex Fang Qi Wong}%
\author[2]{Shalem Leemaqz}%
\author[3]{Teddy Cook}%
\author[1]{Lachlan Angus}%
\author[4]{Kalen Eshin}%
\author[5]{Charlotte Elder}%
\author[5]{Sonia Grover}%
\author[1]{Jeffrey Zajac}%
\author[1]{Ada Cheung}%
\affil[1]{The University of Melbourne Faculty of Medicine Dentistry and Health Sciences}%
\affil[2]{Flinders University College of Medicine and Public Health}%
\affil[3]{ACON}%
\affil[4]{La Trobe University}%
\affil[5]{The University of Melbourne Department of Paediatrics}%


\vspace{-1em}



  
  \date{June 13, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Objective: This descriptive study aimed to assess the prevalence and
characteristics of pelvic pain and explore predictive factors for pelvic
pain in transgender (trans) individuals using testosterone therapy.
Design: Cross-sectional survey. Setting: Online. Sample: Trans people
presumed female at birth, using testosterone for gender-affirmation,
living in Australia, and aged \textgreater{} 16 years. Methods: Logistic
regression was applied to estimate the effect size of the possible
factors contributing to pain after starting testosterone. Main Outcome
Measures: Prevalence and characteristics of pelvic pain following
initiation of testosterone therapy, type and length of testosterone
therapy, menstruation history, and relevant sexual health,
gynaecological and mental health experiences. Results: Among 486
participants (median age 27 years), 351 (72.4\%) reported experiencing
pelvic pain following initiation of testosterone therapy, described most
commonly as in the suprapubic region and as ``cramping''. Median
duration of testosterone therapy was 32 months. Persistent menstruation,
current or previous history of post-traumatic stress disorder, and
experiences of pain with orgasm were associated with higher odds of
pelvic pain after testosterone therapy. No associations were observed
with genital dryness, intrauterine device use, previous pregnancy,
penetrative sexual activities, touching external genitalia, or known
diagnoses of endometriosis, vulvodynia, vaginismus, depression, anxiety,
or obesity. Conclusions: Pelvic pain is common in trans people following
initiation of testosterone therapy. Given the association with
persistent menstruation and orgasm, as well as the known
androgen-sensitivity of the pelvic floor musculature, further research
into pelvic floor muscle dysfunction as a contributor is warranted.%
\end{abstract}%



\sloppy


\textbf{Pelvic pain in transgender people using testosterone therapy: A
national survey}

Sav Zwickl\textsuperscript{1}, Laura Burchill\textsuperscript{1}, Alex
Fang Qi Wong\textsuperscript{1}, Shalem Y Leemaqz\textsuperscript{2},
Teddy Cook\textsuperscript{3}, Lachlan M. Angus\textsuperscript{1,4},
Kalen Eshin\textsuperscript{5}, Charlotte V. Elder\textsuperscript{6},
Sonia R. Grover\textsuperscript{6}, Jeffrey D.
Zajac\textsuperscript{1,4}, Ada S. Cheung\textsuperscript{1,4}

\textsuperscript{1} Trans Health Research group, Department of Medicine
(Austin Health), The University of Melbourne, Victoria, Australia.

\textsuperscript{2} College of Medicine and Public Health, Flinders
University, South Australia, Australia

\textsuperscript{3} ACON Health, Surry Hills, New South Wales,
Australia.

\textsuperscript{4} Gender Clinic, Department of Endocrinology, Austin
Health, Victoria, Australia

\textsuperscript{5} La Trobe University, Victoria, Australia

\textsuperscript{6} Department of Paediatrics, The University of
Melbourne, Australia; Royal Children's Hospital, Melbourne, Australia;
Mercy Hospital for Women, Melbourne, Australia; Austin Health,
Melbourne, Australia.

\textbf{Corresponding author} : Dr Ada Cheung, Austin Health 145 Studley
Road, Heidelberg, Victoria, Australia. Tel: +613 94962260 Fax: +613
94962980 E: adac@unimelb.edu.au

\textbf{Short title: Pelvic pain in trans people on testosterone
therapy}

\textbf{Word Count: 3030}

\textbf{ABSTRACT}

\textbf{Objective:} This descriptive study aimed to assess the
prevalence and characteristics of pelvic pain and explore predictive
factors for pelvic pain in transgender (trans) individuals using
testosterone therapy.

\textbf{Design:} Cross-sectional survey.

\textbf{Setting:} Online.

\textbf{Sample:} Trans people presumed female at birth, using
testosterone for gender-affirmation, living in Australia, and aged
\textgreater{} 16 years.

\textbf{Methods:} Logistic regression was applied to estimate the effect
size of the possible factors contributing to pain after starting
testosterone.

\textbf{Main Outcome Measures:} Prevalence and characteristics of pelvic
pain following initiation of testosterone therapy, type and length of
testosterone therapy, menstruation history, and relevant sexual health,
gynaecological and mental health experiences.

\textbf{Results:} Among 486 participants (median age 27 years), 351
(72.4\%) reported experiencing pelvic pain following initiation of
testosterone therapy, described most commonly as in the suprapubic
region and as ``cramping''. Median duration of testosterone therapy was
32 months. Persistent menstruation, current or previous history of
post-traumatic stress disorder, and experiences of pain with orgasm were
associated with higher odds of pelvic pain after testosterone therapy.
No associations were observed with genital dryness, intrauterine device
use, previous pregnancy, penetrative sexual activities, touching
external genitalia, or known diagnoses of endometriosis, vulvodynia,
vaginismus, depression, anxiety, or obesity.

\textbf{Conclusions:} Pelvic pain is common in trans people following
initiation of testosterone therapy. Given the association with
persistent menstruation and orgasm, as well as the known
androgen-sensitivity of the pelvic floor musculature, further research
into pelvic floor muscle dysfunction as a contributor is warranted.

\textbf{Tweetable Abstract:} Pelvic pain is common in transgender people
using testosterone

\textbf{Funding:} ASC is supported by a NHMRC Investigator Grant
(\#2008956). LMA is supported by the Research Training Program
Scholarship from the Australian Commonwealth Government.

\textbf{Keywords (MeSH):} Transgender persons; pelvic pain;
testosterone; androgens; menstruation disturbances; sexual activity;
sexual function



\textbf{INTRODUCTION}

Pelvic pain in transgender and gender diverse (herein referred to as
trans) people presumed female at birth, who are using testosterone as
gender-affirming hormone therapy (GAHT) is poorly
understood.\textsuperscript{1} Understanding adverse effects of
testosterone therapy is important given that trans people comprise an
estimated 0.5 -- 4.5\% of the adult population,\textsuperscript{2-4} and
there is an increasing demand for gender-affirming healthcare
globally.\textsuperscript{5-7}

Testosterone GAHT which may be given at standard doses or low doses for
people who desire `partial masculinisation', is very effective at
inducing physical changes including significant genital and reproductive
system effects, an increase in body and facial hair, deepening of the
voice, increase in muscle mass, and a decrease in fat
mass.\textsuperscript{8} Menstrual cessation, one of the most desired
aspects of testosterone GAHT, typically occurs within the first six
months of therapy, as well as clitoral enlargement, vulvovaginal atrophy
and increase in libido.\textsuperscript{9, 10} Endometrial changes can
be varied regardless of menstrual cessation with either proliferative
(in 40\%) or atrophic endometrium (in 50\%).\textsuperscript{11} No
significant histopathological changes appear to occur in the
ovaries.\textsuperscript{12}

Pelvic pain in people presumed female is extremely common in the general
population with 17 -- 81\% reporting dysmenorrhoea, 8 -- 22\% reporting
dyspareunia and 2 -- 24\% reporting noncyclical
pain.\textsuperscript{13} Chronic pelvic pain persisting beyond six
months, affects 1 in 7.\textsuperscript{14} Causes are multifactorial
and rarely reflect a single pathological
process.\textsuperscript{15}There is a considerable economic burden on
people experiencing chronic pelvic pain and on healthcare systems
worldwide.\textsuperscript{16}Diagnosis and management can be
challenging and requires an individualised approach.\textsuperscript{17}

As clinicians (gynaecologists, endocrinologists, physiotherapists), we
have seen increasing numbers of trans individuals on testosterone
seeking assistance to relieve symptoms of pelvic pain. However, at the
time of conception of this study, no studies had been published on the
topic of pelvic pain in trans individuals using testosterone GAHT. From
our clinical perspective, we hypothesised that pelvic pain in trans
people using testosterone is predominantly lower abdominal, and similar
to menopause, that atrophic vaginitis and vaginal intercourse would
contribute to pelvic pain.\textsuperscript{18} Further, we hypothesised
that pre-existing endometriosis, vulvodynia, or vaginismus would be risk
factors. Given the limited research on the prevalence and/or the
characteristics of pelvic pain experienced by individuals using
testosterone GAHT this was an exploratory study aiming to identify the
prevalence of pelvic pain in trans people using testosterone GAHT and to
explore potential factors associated with experiencing pelvic pain after
commencing testosterone GAHT.

\textbf{METHODS}

We conducted an online cross-sectional survey of trans individuals using
testosterone GAHT utilising a non-probability snowball sampling
approach. The survey was open~between 28\textsuperscript{th} August 2020
to 31\textsuperscript{st} December 2020 to Australian residents over the
age of~16 years who identified as part of the trans community and were
using testosterone for gender affirmation. The survey was designed
collaboratively by our core team of researchers (SZ, AWFQ, TC, KE) who
are members of the Australian trans community, and clinicians
specialised in trans healthcare.

Survey data were collected and managed using~REDCap~electronic data
capture tools hosted at The University of Melbourne. The study received
ethical and governance approval by the Austin Health Human Research
Ethics Committee (Reference Number HREC/57155/Austin-2019), ACON
Research Ethics Review Committee (Reference Number 2020/03) and the
Thorne Harbour Health Community Research Endorsement Panel (Reference
Number THH/CREP 20-006).

Written informed consent was not obtained, however the survey preamble
outlined that completing the~survey implied consent. Inclusion criteria
were assessed via three screening questions: a) currently living in
Australia; b) identification as trans (``is your gender different to
what was presumed for you at birth?'');~and~c) aged 16 years or older.
Participants in this study were recruited from a larger longitudinal
Australian trans health study known as \emph{TRANSform} . Participants
in\emph{TRANSform} were recruited using a non-probability snowball
sampling approach with recruitment calls posted on social
media~(Facebook and Instagram) and via over~100 trans and gender diverse
community support groups and organisations in Australia.

A total of 670 participants who indicated that they were using
testosterone therapy for gender affirmation were emailed an
individualised~link~to a~survey titled ``Pain experiences in trans men
and trans masculine people using testosterone survey''. A small
participation incentive (AUD\$5 gift card) was provided~for completion.

Survey questions are outlined in detail in the Appendix. In brief,
demographic data and testosterone formulation, dosage and duration of
use were obtained. Participants were asked to provide self-reported
testosterone concentrations. Participants were asked to describe
characteristics and location of pelvic pain and rate severity as well as
compare the presence of pelvic pain prior to and after commencing
testosterone therapy for gender affirmation.

Potential associated factors were explored including persistent
menstruation; presence of genital dryness; history of hysterectomy or
oophorectomy; presence of pain with sexual activities; use of
intrauterine device; known diagnoses of depression, anxiety, PTSD,
endometriosis, vulvodynia (pain in the area around the vulva, not
necessarily with touch), or vaginismus (involuntary tightening of the
muscles around the vagina, not necessarily with penetration). The number
of pregnancies (including miscarriages and terminations) and number of
live births was also determined.

Participant characteristics are reported as frequency (percentage)~for
categorical variables, and median (standard deviation), or median
(interquartile range) as appropriate~for not normally distributed data,
are~included. Logistic regression was used to estimate the effects of
the possible factors contributing to pain on the odds of experiencing
pain after starting testosterone. The factors considered in the
regression were selected prior to performing the analysis based on
potential risk factors for pelvic pain from expert opinion (given the
lack of published research in this field). Results are reported as odds
ratios with corresponding 95\% confidence intervals (CI). This is a
complete case analysis with an alpha level of 5\% (P\textless{}0.05)
considered statistically significant. Statistical
analyses~were~performed using R version 4.0.2 (R Foundation for
Statistical Computing, Vienna, Austria).

\textbf{RESULTS}

Of the 670 trans people presumed female at birth and using testosterone
GAHT who were invited to complete the survey, a total of 506 responded
to the survey. After removing duplicates and incomplete responses, 486
valid responses remained.

\textbf{Characteristics of participants}

Detailed characteristics are outlined in Table 1. The median age of the
486 respondents was 27 years (23, 34). Twenty respondents were aged
between 50 -- 67 years (presumed postmenopausal). Twenty (4.1\%) of the
respondents identified as Aboriginal or Torres Strait Islander, 7
(1.44\%) reported having a variation of sex characteristics (intersex)
and a further 45 (9.26\%) indicated they didn't know if they had a
variation of sex characteristics.

The median duration of testosterone GAHT of participants was 32 months
(14.0, 60.5) with intramuscular testosterone undecanoate injections the
most used formulation. Self-reported total testosterone concentrations
from participants most recent blood tests (N=144) ranged from 0.9 nmol/L
to 56 nmol/L, with a median of 16.2 nmol/L (11.9, 22.0).

\textbf{Characteristics of pain in people experiencing pain after
commencing testosterone therapy}

A total of 351 (72.2\%) of the study sample experienced pelvic pain
after starting testosterone therapy. Of those 351 respondents, 316
(90\%) reported pelvic pain `sometimes' and 35 (10\%) reported pelvic
pain `always or almost always'. Of the 20 respondents aged over 50 years
and presumed postmenopausal, 9 (45\%) reported pelvic pain `sometimes'
and 2 (10\%) reported pelvic pain `always or almost always'.

A majority (N=345, 98.3\%) reported some form of pelvic pain prior to
starting testosterone therapy. This included 190 (65.5\%) who `always or
almost always' and 89 (30.7\%) who `sometimes' experienced pain around
menstruation, 48 (14.3\%) who `always or almost always' and 102 (30.5\%)
who `sometimes' experienced pain around ovulation, and 31 (9.3\%) who
`always or almost always' and 140 (41.9\%) who `sometimes' experienced
pain between menstrual periods.

The most common description of pain was cramping (described by 72.6\%),
followed by aching (58.1\%), stabbing (39.9\%) and sharp (33.9\%). The
pain was most commonly located in the hypogastric region (described by
87.2\% of respondents) (Figure 1). The median score for pain severity
after commencement of testosterone GAHT on a scale from 0 to 10 (most
severe pain) was 6.2 (4.0, 7.7). This was similar to the median score of
6.7 (5.5, 7.8) reported for pain severity around menstruation prior to
commencement of testosterone GAHT. Consistent with this, the median
score in response to the question ``How does the pelvic pain you
experience using testosterone compare to the pelvic pain you experienced
prior to starting testosterone?'' (0 = much less severe, 5 = about the
same to 10 = much more severe), was 4.3 (2.2, 6.8).

\textbf{Associated factors}

Multivariable regression demonstrated that there was a higher odds of
reporting pelvic pain after starting testosterone in people also
experiencing persistent menstruation, or who had a current or previous
diagnosis of PTSD (Table 2). Pelvic pain was also positively associated
with pain with orgasm. A total of 11.3\% (N=39) reported that pelvic
pain `always or almost always' resulted in them stopping sexual activity
or made them consider alternative ways/methods of being sexually active,
and 39.2\% (N=135) reported this was `sometimes' the case.

\textbf{Treatments for pelvic pain in people using testosterone}

The most reported treatments used for relieving pelvic pain included
analgesic medication `pain killers' (56.7\%, N=199), with non-steroidal
anti-inflammatory drugs (NSAID) (Ibuprofen, Diclofenac and Aspirin) and
paracetamol reported most as being helpful (Table 3). Few individuals
had hysterectomy (N=26), or oophorectomy (N=21) and inferences are
limited.

\textbf{DISCUSSION}

\textbf{Main Findings}

Pelvic pain after initiation of testosterone therapy appears to be a
common occurrence, reported by 72.2\% of trans people responding to this
online survey. Cramping pain in the suprapubic (hypogastric) regions
were the most common descriptors. Factors associated with increased odds
of reporting pain with testosterone were persistent menstruation (OR
4.46 (1.33, 14.97)), pain with orgasm (OR 32.72 (10.65, 100.52)), and
current or previous diagnoses of PTSD (OR 2.50 (1.07, 5.85)). NSAIDs
were most commonly used to relieve pain. Of the small number of
participants (n=26) who had undergone hysterectomy, 72\% reported
reduction in pain.

Consistent with our hypothesis and the only other published study
describing pelvic pain in trans people using testosterone GAHT, is the
prevalence of approximately 70\% and the description as cramping, most
commonly in the hypogastrium or suprapubic region, followed by right and
left iliac regions.\textsuperscript{1}

Whilst our exploratory study cannot determine causation or mechanisms of
pain, the increased likelihood of reporting pain in people with
persistent menstruation and orgasm may possibly suggest increased pelvic
floor muscle dysfunction.\textsuperscript{19} It is known that levator
ani, the collective group of pelvic floor muscles consisting of the
deeper layer of pubococcygeus, the iliococcygeus, and the puborectalis,
as well as superficial perineal muscles such as the bulbospongiosus, are
enriched with androgen receptors and exquisitely androgen-sensitive in
male humans, and in male rodents.\textsuperscript{20} Androgen-receptor
knock out mice, and men who have androgen deprivation therapy for
prostate cancer have a marked reduction in the size of the levator ani
muscle.\textsuperscript{21, 22} Androgens have been shown in female
humans and rats to have anabolic effects on pelvic floor
muscles.\textsuperscript{23-25} As such, it is plausible that with
testosterone GAHT may affect the pelvic floor and perineal muscle, and
therefore may contribute to the experience of pain.

Whilst pain from endometriosis has been described to worsen with orgasm
and penetrative sexual activity,\textsuperscript{26} inconsistent with
our hypothesis, our analysis did not show an association between having
a diagnosis of endometriosis, diagnosis of vaginismus, vulvodynia or
genital dryness and pelvic pain.

Participants who reported persistent menstruation had a significantly
higher odds (OR 4.46) of reporting pain after starting testosterone.
Individuals who do have persistent vaginal bleeding would generally be
continuing to have typical rises and falls in estradiol and progesterone
concentrations over the course of a menstrual cycle. Pelvic pain in
people with persistent menstruation may arise from factors such as
dysmenorrhoea from myometrial contractions, the release of inflammatory
mediators that cause endometrial shedding, or pelvic floor muscle
dysfunction. Menstruation with fluctuations in estradiol and
testosterone levels have been demonstrated to affect pelvic floor muscle
activity with significantly higher levels of muscle tone in the luteal
phase relative to the follicular and ovulatory
phases.\textsuperscript{27}

Sexual dysfunction among trans people has been reported to be very
common, likely compounded by increased sexual desire after commencing
testosterone therapy.\textsuperscript{28} However there is little
published research.\textsuperscript{29} Those who had pain with orgasm
had a significantly elevated odds (OR 32.72) of reporting pelvic pain
after starting testosterone GAHT. Pain with orgasm or dysorgasmia, is
one of the least understood and poorly studied areas in sexual medicine,
involving a complex interplay of psychological, neural, vascular, and
endocrine factors. It has been hypothesised that dysorgasmia may be the
result of bladder neck contractions, uterine neuro-inflammation, uterine
contractions and/or pelvic floor musculature
dystonia.\textsuperscript{30, 31} As such, treatment for sexual pain
would be best tailored to the individual with a multidisciplinary
approach involving gynaecology, physical therapy, pain management,
sexual therapy, and mental health professionals who specialize in
chronic pain.\textsuperscript{32} Further research is needed on
aetiologies and evaluating multimodal approaches.

There is a known clear association between chronic pain and PTSD in
people of all genders, explained by both genetic and environmental
factors.\textsuperscript{33, 34} We observed that people who had a
current or previous diagnosis of PTSD had a 150\% higher odds (OR 2.50
(1.07, 5.85)) of reporting pelvic pain after starting testosterone GAHT.
Research has previously shown that in cisgender women with chronic
pelvic pain, that there is an increased prevalence of abuse experiences,
high number of major life events and diagnosis of PTSD (but not
depression).\textsuperscript{35, 36} It is not possible to disentangle
whether experiencing severe pelvic pain causes PTSD or trauma-related
factors that contributed to PTSD also impact upon pelvic pain. One study
in 107 cisgender women suggests that temporally, PTSD appears to precede
the diagnosis of chronic pelvic pain supporting a partial role for PTSD
or its trauma-related trigger in the pathophysiology of chronic pelvic
pain.\textsuperscript{37}

Notably previous studies in people presumed to be female have suggested
an independent association between chronic pelvic pain and anxiety,
depression and mixed anxiety and depressive
disorder.\textsuperscript{38} This was not observed in our analyses
which potentially may be related to the high prevalence of depression
and anxiety among trans people overall.\textsuperscript{39}

\textbf{Clinical implications}

Treatment of pelvic pain can be challenging in the general
population.\textsuperscript{17} A multidisciplinary biopsychosocial
approach which addresses contribution of various factors to the
individual is needed.\textsuperscript{40} This may include medical
therapies, pelvic floor physical therapy, addressing sexual function,
hypersensitivity to pain and psychological factors such as
PTSD.\textsuperscript{40} Respondents to this survey had reported
various self-management strategies. Over the counter pain-relieving
medications in the form of paracetamol, NSAIDs and heat were the most
frequent strategies reported to manage pelvic pain. In a Cochrane review
of management of dysmenorrhea, NSAIDs and heat were recommended as first
line treatment to alleviate pain symptoms produced by the release of
prostaglandins from the endometrial lining. It is recommended that these
strategies are initiated 48 hours prior to onset of menses. Irregular
bleeding and amenorrhea may explain the ineffectiveness of these
strategies in this population; with limited warning of the onset of
breakthrough bleeding episodes.\textsuperscript{41}

Many trans people seek hysterectomy and/or oophorectomy as part of
gender-affirmation, or due to pelvic pain or ongoing or abnormal
bleeding. Of the individuals in this study who had a hysterectomy,
pelvic pain was the most common indicator for surgery (64\%), followed
by gender dysphoria (48\%). A total of 72\% (N=18) reported relief of
pelvic pain symptoms after hysterectomy. Whilst the overall number of
respondents undergoing a hysterectomy and/or oophorectomy was too small
for meaningful statistical analyses, surgery would indeed cure
persistent menstruation which was much more likely in people reporting
pain after commencing testosterone therapy. Moreover, cisgender women
have also reported resolution or decrease in pelvic pain following
hysterectomy.\textsuperscript{42} It must be noted that five individuals
(20\%) in this study reported no change in their pelvic pain and two
(8\%) reported an increase in pelvic pain following hysterectomy.
Further research is warranted.

Whilst further studies need to evaluate the possibility of high pelvic
floor muscle tone as a causative factor for pelvic pain in trans people
after starting testosterone for gender affirmation, a recent systematic
review of pelvic floor physical therapy to release myofascial trigger
points found positive beneficial effects, particularly in people with
chronic pelvic pain and dyspareunia.\textsuperscript{43} Given the lack
of current treatments available to alleviate often debilitating pelvic
pain in trans people on testosterone therapy, pelvic floor physical
therapy may be a low-risk, treatment strategy to trial in addition to
simple analgesics.\textsuperscript{40}

\textbf{Strengths and Limitations}

This study has multiple limitations. As this was an online survey
recruited through non-probability snowball sampling, this may have
encouraged a greater proportion of responders who were younger
individuals and may not be representative of the broader trans
community. Of the 670 people participating in the larger\emph{TRANSform}
study who indicated they were using testosterone therapy and were
invited to participate in this testosterone and pain study, 486
responded, corresponding to a response rate of 72.5\%. There may well
have been responder bias, with individuals experiencing pain syndromes
more likely to respond and overrepresenting the proportion of
individuals on testosterone experiencing pelvic pain. Further, as
participants were asked to recall experiences from prior to commencing
testosterone, there is the possibility of recall bias. Medical
conditions and testosterone levels were self-reported, and we were
unable to confirm diagnoses or blood test results. We also acknowledge
that questions regarding penetrative sexual activities did not specify
vaginal or anal penetration. Standardised questionnaires for sexual
dysfunction were not included, and these are not validated for trans and
gender diverse populations. The impact of testosterone therapy on sexual
function warrants further investigation.

Despite the limitations, this survey is the largest study to date
exploring pelvic pain in trans people using testosterone therapy and is
hypothesis generating for future studies examining the pathophysiology
of, or the effectiveness of interventions on pelvic pain.

\textbf{CONCLUSION}

Pelvic pain occurring after commencing testosterone GAHT is frequently
reported by trans people. The increased likelihood of reporting pain in
people with persistent menstruation, and orgasm, as well as the known
androgen-sensitivity of the pelvic floor musculature warrant further
research on pelvic floor muscle dysfunction as a
contributor.\textsuperscript{19} Until further evidence is available, a
tailored multidisciplinary trauma-informed approach addressing the needs
of the individual with pelvic pain should be provided, which may
encompass pain management, sexual function, addressing persistent
menstruation and mental health.

\textbf{ACKNOWLEDGEMENTS}

The authorship team includes trans people of diverse genders including
female, male and non-binary.~Authors would like to thank MCATS
(Melbourne Clinical~and Translational Sciences research platform), for
the administrative and technical support that greatly facilitated this
research. ASC is supported by an Australian Government National Health
and Medical Research Council Early Career Fellowship (\#1143333),
Investigator Grant (\#2008956), and~The University of Melbourne Dame
Kate Campbell Fellowship.~LMA is supported by the Research Training
Program Scholarship from the Australian Commonwealth Government.

\textbf{DISCLOSURE OF INTERESTS}

The authors report no conflicts of interest.

\textbf{AUTHOR~CONTRIBUTIONS}

\textbf{SZ:} Conceptualization, Data Curation, Formal analysis,
Methodology, Project administration, Writing - original draft, Writing -
review \& editing. \textbf{LB:} Conceptualization, Methodology, Writing
- original draft, Writing - review \& editing.
\textbf{AFQW:}Conceptualization, Formal analysis, Methodology, Writing -
review \& editing. \textbf{SYL:} Formal analysis, Writing - review \&
editing.\textbf{TC:} Conceptualization, Methodology, Writing - review \&
editing. \textbf{LMA:} Conceptualization, Methodology, Writing - review
\& editing. \textbf{KE:} Conceptualization, Methodology, Writing -
review \& editing. \textbf{CVE:} Conceptualization, Methodology, Writing
- review \& editing. \textbf{SRG:} Conceptualization, Methodology,
Writing - review \& editing. \textbf{JDZ:} Conceptualization,
Methodology, Supervision, Writing - review \& editing. \textbf{ASC} :
Conceptualization, Methodology, Project administration, Funding
Acquisition, Supervision, Writing - original draft, Writing - review \&
editing.

\textbf{DETAILS OF ETHICS APPROVAL}

The study received ethical and governance approval by the Austin Health
Human Research Ethics Committee (Reference Number
HREC/57155/Austin-2019), ACON Research Ethics Review Committee
(Reference Number 2020/03) and the Thorne Harbour Health Community
Research Endorsement Panel (Reference Number THH/CREP 20-006).

\textbf{FUNDING}

ASC is supported by an Australian Government National Health and Medical
Research Council Early Career Fellowship (\#1143333), Investigator Grant
(\#2008956), and The University of Melbourne Dame Kate Campbell
Fellowship. LMA is supported by the Research Training Program
Scholarship from the Australian Commonwealth Government. ~

\textbf{REFERENCES}

1. Grimstad FW, Stowell JT, Gaddis M. Survey of Experiences of
Transgender and Gender Nonbinary Patients During Imaging Encounters and
Opportunities for Improvement. AJR Am J Roentgenol. 2020;215(5):1136-42.

2. Crissman HP, Berger MB, Graham LF, Dalton VK. Transgender
demographics: a household probability sample of US adults, 2014.
American journal of public health. 2017;107(2):213-5.

3. \selectlanguage{ngerman}Åhs JW, Dhejne C, Magnusson C, Dal H, Lundin A, Arver S, et al.
Proportion of adults in the general population of Stockholm County who
want gender-affirming medical treatment. PLoS One. 2018;13(10):e0204606.

4. Lai M-C, Chiu Y-N, Gadow KD, Gau SS-F, Hwu H-G. Correlates of gender
dysphoria in Taiwanese university students. Archives of Sexual Behavior.
2010;39(6):1415-28.

5. Cheung AS, Ooi O, Leemaqz S, Cundill P, Silberstein N, Bretherton I,
et al. Sociodemographic and clinical characteristics of transgender
adults in Australia. Transgender Health. 2018;3(1):229-38.

6. Delahunt JW, Denison HJ, Sim DA, Bullock JJ, Krebs JD. Increasing
rates of people identifying as transgender presenting to Endocrine
Services in the Wellington region. NZ Med J. 2018;131(1468):33-42.

7. Telfer MM, Tollit MA, Feldman D. Transformation of health-care and
legal systems for the transgender population: the need for change in
Australia. Journal of Paediatrics \& Child Health. 2015;51(11):1051-3.

8. Cheung AS, Wynne K, Erasmus J, Murray S, Zajac JD. Position statement
on the hormonal management of adult transgender and gender diverse
individuals. Medical Journal of Australia. 2019;211(3):127-33.

9. Defreyne J, Vanwonterghem Y, Collet S, Iwamoto SJ, Wiepjes CM, Fisher
AD, et al. Vaginal bleeding and spotting in transgender men after
initiation of testosterone therapy: A prospective cohort study (ENIGI).
International journal of transgender health. 2020;21(2):163-75.

10. Defreyne J, Elaut E, Kreukels B, Fisher AD, Castellini G,
Staphorsius A, et al. Sexual Desire Changes in Transgender Individuals
Upon Initiation of Hormone Treatment: Results From the Longitudinal
European Network for the Investigation of Gender Incongruence. J Sex
Med. 2020;17(4):812-25.

11. Hawkins M, Deutsch MB, Obedin-Maliver J, Stark B, Grubman J, Jacoby
A, et al. Endometrial findings among transgender and gender nonbinary
people using testosterone at the time of gender-affirming hysterectomy.
Fertil Steril. 2021;115(5):1312-7.

12. Grimstad FW, Fowler KG, New EP, Ferrando CA, Pollard RR, Chapman G,
et al. Ovarian histopathology in transmasculine persons on testosterone:
a multicenter case series. The Journal of Sexual Medicine.
2020;17(9):1807-18.

13. Latthe P, Latthe M, Say L, Gulmezoglu M, Khan KS. WHO systematic
review of prevalence of chronic pelvic pain: a neglected reproductive
health morbidity. BMC Public Health. 2006;6:177.

14. Mathias SD, Kuppermann M, Liberman RF, Lipschutz RC, Steege JF.
Chronic pelvic pain: prevalence, health-related quality of life, and
economic correlates. Obstet Gynecol. 1996;87(3):321-7.

15. Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Fedele
L. Chronic pelvic pain in women: etiology, pathogenesis and diagnostic
approach. Gynecol Endocrinol. 2009;25(3):149-58.

16. Huang G, Le AL, Goddard Y, James D, Thavorn K, Payne M, et al. A
systematic review of the cost of chronic pelvic pain in women. J Obstet
Gynaecol Can. 2021.

17. Passavanti MB, Pota V, Sansone P, Aurilio C, De Nardis L, Pace MC.
Chronic Pelvic Pain: Assessment, Evaluation, and Objectivation. Pain Res
Treat. 2017;2017:9472925.

18. Rahn DD, Carberry C, Sanses TV, Mamik MM, Ward RM, Meriwether KV, et
al. Vaginal estrogen for genitourinary syndrome of menopause: a
systematic review. Obstet Gynecol. 2014;124(6):1147-56.

19. Faubion SS, Shuster LT, Bharucha AE. Recognition and management of
nonrelaxing pelvic floor dysfunction. Mayo Clin Proc. 2012;87(2):187-93.

20. Johansen JA, Breedlove SM, Jordan CL. Androgen receptor expression
in the levator ani muscle of male mice. Journal of neuroendocrinology.
2007;19(10):823-6.

21. Davey RA, Clarke MV, Russell PK, Rana K, Seto J, Roeszler KN, et al.
Androgen Action via the Androgen Receptor in Neurons Within the Brain
Positively Regulates Muscle Mass in Male Mice. Endocrinology.
2017;158(10):3684-95.

22. Cheung AS, Cunningham C, Ko DD, Ly V, Gray H, Hoermann R, et al.
Selective Loss of Levator Ani and Leg Muscle Volumes in Men Undergoing
Androgen Deprivation Therapy. J Clin Endocrinol Metab.
2019;104(6):2229-38.

23. Ho MH, Bhatia NN, Bhasin S. Anabolic effects of androgens on muscles
of female pelvic floor and lower urinary tract. Curr Opin Obstet
Gynecol. 2004;16(5):405-9.

24. Mammadov R, Simsir A, Tuglu I, Evren V, Gurer E, Özyurt C. The
effect of testosterone treatment on urodynamic findings and
histopathomorphology of pelvic floor muscles in female rats with
experimentally induced stress urinary incontinence. Int Urol Nephrol.
2011;43(4):1003-8.

25. Ponnusamy S, Sullivan RD, Thiyagarajan T, Tillmann H, Getzenberg RH,
Narayanan R. Tissue Selective Androgen Receptor Modulators (SARMs)
Increase Pelvic Floor Muscle Mass in Ovariectomized Mice. J Cell
Biochem. 2017;118(3):640-6.

26. Fairbanks F, Abdo CH, Baracat EC, Podgaec S. Endometriosis doubles
the risk of sexual dysfunction: a cross-sectional study in a large
amount of patients. Gynecol Endocrinol. 2017;33(7):544-7.

27. Micussi MT, Freitas RP, Angelo PH, Soares EM, Lemos TM, Maranhão TM.
Is there a difference in the electromyographic activity of the pelvic
floor muscles across the phases of the menstrual cycle? J Phys Ther Sci.
2015;27(7):2233-7.

28. Kerckhof ME, Kreukels BPC, Nieder TO, Becker-Hébly I, van de Grift
TC, Staphorsius AS, et al. Prevalence of Sexual Dysfunctions in
Transgender Persons: Results from the ENIGI Follow-Up Study. J Sex Med.
2019;16(12):2018-29.

29. Sorensen J, Bautista KE, Lamvu G, Feranec J. Evaluation and
Treatment of Female Sexual Pain: A Clinical Review. Cureus.
2018;10(3):e2379.

30. Barnas JL, Pierpaoli S, Ladd P, Valenzuela R, Aviv N, Parker M, et
al. The prevalence and nature of orgasmic dysfunction after radical
prostatectomy. BJU Int. 2004;94(4):603-5.

31. Yong PJ. Clinical Conundrum: A 33-Year-Old With Pain Post-Orgasm and
a History of Endometriosis. J Obstet Gynaecol Can. 2020;42(5):625-8.

32. Committee Opinion No 673: Persistent Vulvar Pain. Obstet Gynecol.
2016;128(3):e78-e84.

33. Fishbain DA, Pulikal A, Lewis JE, Gao J. Chronic Pain Types Differ
in Their Reported Prevalence of Post -Traumatic Stress Disorder (PTSD)
and There Is Consistent Evidence That Chronic Pain Is Associated with
PTSD: An Evidence-Based Structured Systematic Review. Pain Medicine.
2017;18(4):711-35.

34. Gasperi M, Panizzon M, Goldberg J, Buchwald D, Afari N.
Posttraumatic Stress Disorder and Chronic Pain Conditions in Men: A Twin
Study. Psychosom Med. 2021;83(2):109-17.

35. Heim C, Ehlert U, Hanker JP, Hellhammer DH. Abuse-related
posttraumatic stress disorder and alterations of the
hypothalamic-pituitary-adrenal axis in women with chronic pelvic pain.
Psychosom Med. 1998;60(3):309-18.

36. Meltzer-Brody S, Leserman J, Zolnoun D, Steege J, Green E, Teich A.
Trauma and posttraumatic stress disorder in women with chronic pelvic
pain. Obstet Gynecol. 2007;109(4):902-8.

37. Chelimsky GG, Yang S, Sanses T, Tatsuoka C, Buffington CAT, Janata
J, et al. Autonomic neurophysiologic implications of disorders comorbid
with bladder pain syndrome vs myofascial pelvic pain. Neurourol Urodyn.
2019;38(5):1370-7.

38. Siqueira-Campos VME, Da Luz RA, de Deus JM, Martinez EZ, Conde DM.
Anxiety and depression in women with and without chronic pelvic pain:
prevalence and associated factors. J Pain Res. 2019;12:1223-33.

39. Bretherton I, Thrower E, Zwickl S, Wong A, Chetcuti D, Grossmann M,
et al. The Health and Well-Being of Transgender Australians: A National
Community Survey. LGBT health. 2021;8(1):42-9.

40. Grinberg K, Sela Y, Nissanholtz-Gannot R. New Insights about Chronic
Pelvic Pain Syndrome (CPPS). International journal of environmental
research and public health. 2020;17(9).

41. Grimstad F, Kremen J, Shim J, Charlton BM, Boskey ER. Breakthrough
Bleeding in Transgender and Gender Diverse Adolescents and Young Adults
on Long-Term Testosterone. J Pediatr Adolesc Gynecol. 2021;34(5):706-16.

42. Hillis SD, Marchbanks PA, Peterson HB. The effectiveness of
hysterectomy for chronic pelvic pain. Obstetrics \& Gynecology.
1995;86(6):941-5.

43. van Reijn-Baggen DA, Han-Geurts IJM, Voorham-van der Zalm PJ, Pelger
RCM, Hagenaars-van Miert C, Laan ETM. Pelvic Floor Physical Therapy for
Pelvic Floor Hypertonicity: A Systematic Review of Treatment Efficacy.
Sex Med Rev. 2021.

\textbf{TABLES AND FIGURES}

\textbf{Table 1. Characteristics of the study sample}\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
Characteristic & N & \%\tabularnewline
\midrule
\endhead
Age (N=479) & &\tabularnewline
16 -- 25 & 192 & 40.3\tabularnewline
26 -- 35 & 190 & 39.7\tabularnewline
36 -- 45 & 62 & 12.9\tabularnewline
46 -- 55 & 25 & 5.2\tabularnewline
56 -- 65 & 9 & 1.9\tabularnewline
66 -- 75 & 1 & 0.2\tabularnewline
Limited Gender Category (N=486) & &\tabularnewline
Man/Trans man & 373 & 76.8\tabularnewline
Non-binary & 113 & 23.3\tabularnewline
Testosterone Formulation (N=486)* & &\tabularnewline
Testosterone undecanoate (Reandron) & 358 & 73.7\tabularnewline
Testosterone enanthate (Primoteston depot) & 38 & 7.8\tabularnewline
Testosterone esters (Sustanon 250) & 10 & 2.1\tabularnewline
Testosterone 1\% gel (Testogel) & 62 & 12.8\tabularnewline
Testosterone 2\% gel (Testavan) & 10 & 2.1\tabularnewline
Testosterone 5\% cream (Androforte 5) & 11 & 2.3\tabularnewline
Testosterone 2\% cream (Androforte 2) & 1 & 0.2\tabularnewline
Other & 3 & 0.6\tabularnewline
Self-Reported Testosterone Dosage (N=486) & &\tabularnewline
Full dose & 430 & 87.7\tabularnewline
Half dose & 33 & 6.8\tabularnewline
Quarter dose & 9 & 1.9\tabularnewline
Other (e.g., change in dosage) & 14 & 3.7\tabularnewline
Self-reported Testosterone Blood Concentrations nmol/L (N=144) &
&\tabularnewline
0.0 -- 4.9 & 5 & 3.5\tabularnewline
5.0 -- 9.9 & 18 & 12.5\tabularnewline
10.0 -- 14.9 & 38 & 26.4\tabularnewline
15.0 -- 19.9 & 35 & 24.3\tabularnewline
20.0 -- 24.9 & 23 & 16.0\tabularnewline
25.0 -- 29.9 & 14 & 9.7\tabularnewline
30.00+ & 11 & 7.6\tabularnewline
Consistency of testosterone use (N=485) & &\tabularnewline
Consistent use since starting & 426 & 87.8\tabularnewline
Regularly stop and start use & 10 & 2.1\tabularnewline
Other (e.g., change in dosage or formulation) & 46 & 9.5\tabularnewline
Unsure/Prefer not to say & 3 & 0.6\tabularnewline
\bottomrule
\end{longtable}

*Multiple responses allowed for this question so total responses do not
sum to 100\%

\textbf{Table 2. Factors associated with pain after starting
testosterone therapy.}\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Factors}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Pelvic pain since commencing testosterone (N=351)} \textbf{N
(\%)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{No pelvic pain since commencing testosterone (N=122)} \textbf{N
(\%)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Odds ratio (95\% CI)*}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{P-value*}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Persistent menstruation Yes No Unsure/Prefer not to say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
53 (16\%) 266 (80\%) 13 (4\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
12 (11\%) 94 (86\%) 3 (3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
4.46 (1.33, 14.97)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{0.015}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Genital dryness Sometimes/Always Never Unsure/Prefer not to say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
192 (55\%) 140 (40\%) 19 (5\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
50 (41\%) 65 (54\%) 6 (5\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1.82 (0.89, 3.74)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.103\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Intrauterine device in situ Yes No Unsure/Prefer not to say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
38 (11\%) 312 (89\%) 1 (0.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
9 (7\%) 112 (93\%) 0\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1.74 (0.37, 8.11)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.480\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Duration of testosterone therapy (months) Median (IQR)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
34 (17, 61)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
24 (10, 57)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1.00 (1.00, 1.01)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.524\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Diagnosis of endometriosis Yes No Unsure/Prefer not to say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
39 (11\%) 302 (86\%) 9 (3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
3 (3\%) 117 (97\%) 1 (0.8\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
4.41 (0.41, 47.54)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.221\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Diagnosis of vulvodynia or vaginismus Yes No\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
67 (19\%) 284 (81\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
8 (7\%) 114 (93\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1.95 (0.66, 5.78)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.230\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Previous pregnancy None One or more Unsure/Prefer not to say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
311 (89\%) 39 (11\%) 1 (0.3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
109 (90\%) 12 (10\%) 0 (0.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1.17 (0.31, 4.45)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.821\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Current or previous PTSD Current/previous Never Unsure/Prefer not to
say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
122 (35\%) 194 (56\%) 32 (9\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
17 (14\%) 92 (76\%) 12 (10\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
2.50 (1.07, 5.85)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{0.035}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Current or previous depression Current/previous Never Unsure/Prefer not
to say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
292 (83\%) 50 (14\%) 9 (3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
82 (67\%) 34 (28\%) 6 (5\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
2.62 (0.86, 7.98)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.091\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Current or previous anxiety Current/previous Never Unsure/Prefer not to
say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
280 (80\%) 59 (17\%) 11 (3\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
78 (65\%) 35 (29\%) 7 (6\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.97 (0.32, 2.95)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.961\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Obesity Body mass index \textless{}30 kg/m\textsuperscript{2} Body mass
index [?]30 kg/m\textsuperscript{2}\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
232 (67\%) 116 (33\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
96 (80\%) 24 (20\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1.38 (0.62, 3.07)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.425\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Pain with orgasm Sometimes/Always Never Unsure/Prefer not to say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
208 (59.3) 125 (36.1) 13 (3.8)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
10 (8.6) 99 (85.3) 7 (6.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
32.72 (10.65, 100.52)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textbf{\textless{}0.0001}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Pain with touching of external genitalia Sometimes/Always Never
Unsure/Prefer not to say\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
127 (36.2) 212 (61.6) 5 (1.5)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
23 (19.8) 93 (80.2) 0 (0.0)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.84 (0.32, 2.16)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.715\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Pain with penetrative sexual activities Sometime/Always Never
Unsure/Prefer not to say Don't do penetrative activities\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
230 (66.5) 60 (17.3) 9 (2.6) 47 (13.6)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
50 (43.1) 29 (25.0) 2 (1.7) 35 (30.2)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
1.18 (0.58, 2.40)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.640\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

'Unsure/Prefer not to say' was treated as missing and excluded from
analysis; *Odds ratio (95\% CI) and P-values from logistic regression
mutually adjusted for all factors presented in table.

\textbf{Table 3. Treatments for pelvic pain in people using
testosterone}\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\textbf{Characteristic} & \textbf{N} & \textbf{\%}\tabularnewline
\midrule
\endhead
Types of treatment reported as helpful (N=351)* & &\tabularnewline
Pain killers & 199 & 56.7\tabularnewline
Heat & 160 & 45.6\tabularnewline
Testosterone therapy & 77 & 21.9\tabularnewline
Other (e.g. massage, progesterone implant, IUD) & 63 &
17.9\tabularnewline
Cannabis & 40 & 11.4\tabularnewline
Exercise & 39 & 11.1\tabularnewline
Unsure/Prefer not to say & 22 & 6.3\tabularnewline
Estrogen containing vaginal cream or pessary & 16 & 4.6\tabularnewline
Progesterone tablet & 9 & 2.6\tabularnewline
Danazol tablets & 0 & 0.0\tabularnewline
GnRH agonists & 0 & 0.0\tabularnewline
Types of painkillers reported as helpful (N=351)* & &\tabularnewline
Non-steroidal anti-inflammatory drugs (Ibuprofen, Diclofenac and
Aspirin) & 163 & 46.4\tabularnewline
Paracetamol & 108 & 30.8\tabularnewline
Combination of paracetamol and Ibuprofen & 47 & 13.4\tabularnewline
Morphine & 34 & 9.7\tabularnewline
Tramadol & 10 & 2.8\tabularnewline
Types of treatment reported as unhelpful (N=351)* & &\tabularnewline
Pain killers & 64 & 18.2\tabularnewline
Exercise & 61 & 17.4\tabularnewline
Unsure/Prefer not to say & 52 & 14.8\tabularnewline
Heat & 48 & 13.7\tabularnewline
Testosterone therapy & 32 & 9.1\tabularnewline
Progesterone tablet & 21 & 6.0\tabularnewline
Other (e.g. progesterone implant, IUD) & 16 & 4.6\tabularnewline
Estrogen containing vaginal cream or pessary & 12 & 3.4\tabularnewline
Cannabis & 12 & 3.4\tabularnewline
GnRH agonists & 2 & 0.6\tabularnewline
Danazol tablets & 1 & 0.3\tabularnewline
Impact of hysterectomy on pain (N=25) & &\tabularnewline
(0 to 29) Pain is worse since hysterectomy & 2 & 8.0\tabularnewline
(30 to 69) Pain is about the same & 5 & 20.0\tabularnewline
(70 to 100) Pain is better since hysterectomy & 18 & 72.0\tabularnewline
Reasons for hysterectomy (N=25)* & &\tabularnewline
Pelvic pain & 16 & 64\tabularnewline
Gender dysphoria & 12 & 48\tabularnewline
Ongoing bleeding & 5 & 20\tabularnewline
Other (e.g. Cancer diagnosis, phalloplasty, endometriosis) & 11 &
44\tabularnewline
Impact of oophorectomy on pain (N=21) & &\tabularnewline
(score 0 to 29) Pain is worse since oophorectomy & 3 &
14.3\tabularnewline
(score 30 to 69) Pain is about the same & 4 & 19.0\tabularnewline
(score 70 to 100) Pain is better since oophorectomy & 14 &
66.7\tabularnewline
\bottomrule
\end{longtable}

*Multiple responses allowed for this question so total responses do not
sum to 100\%

\textbf{Figure 1. Diagram of abdominal and pelvic regions (N=351)}

Figure Legend: Location of pelvic pain selected by number of respondents
describing pelvic pain since starting testosterone therapy. Multiple
responses allowed for this question so total responses do not sum to
100\%.

\textbf{APPENDIX}

Testosterone use was explored through the questions ``What date
(approximately) did you start testosterone therapy?'' and ``What type of
testosterone are you currently using?'' with fixed-response options that
included all commonly available forms of testosterone (injections,
gels/creams, implants). Participants were also asked ``How have you been
using testosterone?'', with the multi-choice options of consistent,
intermittent or `other' use, and ``What dose of testosterone are you
on?'' with fixed-response options of full, half, quarter or `other'
dose. Testosterone blood levels were ascertained with the question
``What were your testosterone levels on your most recent blood test?
{[}nmol/L{]}''.

Experiences of pelvic pain before using testosterone were assessed with
fixed-response options (always or almost always, sometimes, never) to
``Did you ever experience pelvic pain prior to starting testosterone
therapy?''. Those participants who indicated they experienced
menstruation before starting testosterone, were also asked fixed
response options (always, almost always, sometimes and never) to ``Did
you experience pain around the time of bleeding/periods? (i.e. in the
couple days before or during bleeding/periods)'', ``Did you experience
pelvic pain between bleeding/periods?'' and ``Did you experience pelvic
pain at or around the time of ovulation?''. Participants were also asked
to rate their pain with on a scale of 0 to 10 with 10 = most severe
pain.

Experiences of pelvic pain since the commencement of testosterone GAHT
were assessed with fixed response options (always or almost always,
sometimes, never) to ``Have you experienced pelvic pain since commencing
testosterone therapy?''. Those participants who experienced pelvic pain
since commencement of testosterone, were then asked to rate the severity
of this pain on a scale of 0 to 10, with 10 = most severe pain. Those
who reported pelvic pain both prior to and since commencement of
testosterone, were asked ``How does the pelvic pain you experience using
testosterone compare to the pelvic pain you experienced prior to
starting testosterone?'' on a scale of 0 = much less severe to 10 = much
more severe. Participants were also asked to describe their pain from
fixed-response options, and to ascertain the location of the pelvic
pain, participants were asked to locate the pain on a diagram of the
abdominal and pelvic regions (Figure 1).

The effectiveness of treatment strategies were assessed with
fixed-response options to ``What treatment or strategies (if any) have
eased your pelvic pain?'' and ``What treatments or strategies have you
tried that have not worked?''.

The effect of testosterone use on menstruation was assessed by asking
those participants who reported experiencing bleeding/periods prior to
starting testosterone to provide a Yes or No response to ``Have your
periods/bleeding stopped since starting testosterone?''. Those
participants who had experienced cessation in menstruation were asked to
provide a fixed-response to ``How long did it take your periods/bleeding
to stop after starting testosterone?''. Participants were also asked if
they experienced genital dryness.

Associations between pelvic pain and sexual activity were also explored.
Those participants who indicated that they were sexually active
(including masturbation) were asked whether they experienced pelvic pain
or other pain during a range of sexual activities. This included
fixed-response options (always or almost always, sometimes, never) to
``Does touching of your external genitalia cause pain?'', ``Do
penetrative sexual activities, provoke pain?'' and ``Does orgasm cause
pain?''. The impact of pelvic pain on sexual activity was assessed with
fixed-response options (always or almost always, sometimes, never) to
``Does the pelvic pain stop you or make you consider alternative
ways/methods of being sexually active?''.

Diagnosed pelvic conditions were explored to identify potential
treatments or factors related to pelvic pain. This included Yes or No
responses to ``Have you ever had an \emph{intrauterine device (IUD)?''}
, and whether they had ever been diagnosed with endometriosis,
vulvodynia (pain in the area around the vulva, not necessarily with
touch), or vaginismus (involuntary tightening of the muscles around the
vagina, not necessarily with penetration). The number of pregnancies
(including miscarriages and terminations) and number of live births was
also determined.

Participants were asked if they had previously undergone a hysterectomy
or oophorectomy. Those who indicated they had a hysterectomy, were asked
``What was the reason for the hysterectomy?'' with fixed-response
options and ``How has the hysterectomy affected your pelvic pain?'' on a
scale of 0 = pain is far worse to 10 = pain is far better. Similarly,
those participants who indicated they had an oophorectomy, were asked
``How has the oophorectomy affected your pelvic pain?'' on a scale of 0
= pain is far worse to 10 = pain is far better.

To assess any associations between pelvic pain and mental health,
participants were also asked whether they had a previous or current
diagnosis of post-traumatic stress disorder (PTSD), depression, or
anxiety. Self-reported height and weight provided an approximation of
body mass index (BMI).\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1-abdomen/Figure-1-abdomen}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

