How low can you go? Titrating the lowest effective dose of cyproterone acetate for transgender and gender diverse people who request feminizing hormones

Abstract

Background: Administration of cyproterone acetate (CPA), to reduce the production and effects of testosterone, is often part of clinical regimens for trans individuals seeking feminization. Due to the potency of CPA, there are dose-related side effects and over-suppression of testosterone that can occur.

Aim: This study aimed to determine the lowest possible dosing of CPA to reduce dose-related side effects while still achieving patient goals.

Methods: This uncontrolled intervention study recruited participants seeking full-dose feminizing hormone treatment from across six study sites in Australia (primary care and sexual health clinics). Administration of CPA was defined using a titration protocol to achieve the target testosterone range (0.5–1.5 nmol/L). Descriptive analysis was conducted to investigate various factors of interest that pertained to the aims of the study.

Results: A total of 74 participants commenced the study. There was a high rate of loss to follow-up with 62.2% (46/74) completing the protocol endpoint. Of participants who completed the protocol, 74.0% (34/46) were able to achieve the target T-range (0.5–1.5 nmol/L) and 41.3% (19/46) were titrated to the lowest CPA level (12.5 mg cyproterone twice weekly).

Discussion: This study provided clinical evidence that lower and alternate-day dosing CPA can achieve adequate testosterone suppression in individuals undergoing feminizing gender affirming hormone therapy (GAHT). This provides promising evidence of the acceptability of lowering CPA dosing to reduce the impacts of CPA-related side effects and improve the outcomes and experiences of individuals undergoing GAHT.

Keywords:

• Cyproterone acetate
• feminization
• gender affirming hormone therapy
• testosterone
• transgender

Introduction

An increasing number of trans (binary or non-binary) individuals are pursuing Gender Affirming Hormone Therapy (GAHT) as part of a constellation of processes targeting gender affirmation (D’Hoore & T’Sjoen, 2022). Multiple studies have shown the positive impact that GAHT can have on individuals, such as improving quality of life and wellbeing (Asscheman et al., 2011; Bauer et al., 2015; Murad et al., 2010; Tucker et al., 2018; van Leerdam et al., 2021; White Hughto & Reisner, 2016). As evidenced by a review conducted by Fowler and colleagues, (Fowler et al., 2023) common across the 28 included papers was a belief that GAHT was a life-changing and immensely positive experience, despite the potential for emotional tumult.

For trans individuals seeking feminization, treatment usually consists of a combination of feminizing hormones (e.g. estradiol) and an anti-androgen to block the release and/or effect of testosterone to facilitate this process (Cundill, 2020). When suppressing the production of testosterone, most prescribers target the pre-menopausal female range (0.4-2nmol/mL) (Angus et al., 2019; Cheung et al., 2019; Clark et al., 2019). Cyproterone acetate (CPA), and spironolactone are the two anti-androgens most commonly prescribed by primary care clinicians in Australia (Angus et al., 2019; Cundill, 2020). CPA is more potent than spironolactone and found to significantly reduce serum testosterone levels, making it the predominant anti-androgen prescribed by Australian clinicians (Angus et al., 2019; Bretherton et al., 2019; Burinkul et al., 2021).

The administration of CPA between 25-50mg daily is safe while maintaining clinical efficacy (Fung et al., 2017; Wierckx et al., 2012). However due to the potency of CPA, there can be dose-dependant side effects, such as increased incidence of depression, hepatic failure, asymptomatic hyperprolactinemia, and meningioma that have been noted among several studies (Bergoglio et al., 2013; Burinkul et al., 2021; Gazzeri et al., 2007; Kim et al., 2014; Knight & McDonald, 2013; Ter Wengel et al., 2016; Thole et al., 2004), however, these side-effects are considered uncommon. Additionally, over-suppression of testosterone can occur, which can result in reductions in energy levels and libido, and may be linked to increased risk of cardiovascular disease (Halpern & Brannigan, 2019; Rako, 2000; Spry et al., 2009). Therefore, determining the lowest possible dosing of CPA is a vital clinical consideration to improve the GAHT experiences and health outcomes of individuals seeking feminization.

One previous study has explored the impact on testosterone suppression of CPA dosing of 10 mg daily, 25 mg daily, 50 mg daily, 100 mg daily or no CPA dosage (Kuijpers et al., 2021). Over the course of one year, results indicated CPA was able to adequately reduce testosterone below 2 nmol/L. However, no significant differences were identified between levels of CPA and testosterone suppression, indicating 100 mg doses were similarly effective to 10 mg doses. It is important to note that within this sample only 4 participants were at a dosage of 10 mg daily, compared to 234 and 599 at 25 mg and 50 mg daily doses respectively. However, this evidence is promising, and future research is necessary to extend our understanding of the lowest dosing of CPA to enact clinically significant changes in testosterone levels. Namely, the efficacy of <10mg of CPA and alternate day dosing. Similar to CPA, estrogen can also have an effect on testosterone (Leinung & Joseph, 2020), therefore, it is important to consider the combine effect of CPA and estrogen dose on testosterone in individuals undergoing feminization.

This uncontrolled intervention study aimed to extend previous literature to determine the lowest biochemically effective dosage of CPA to suppress testosterone and is guided by three research questions: (1) Is a protocol of successive dose reduction based on biochemical markers effective at suppressing testosterone? (2) what is the lowest biochemically effective dosage of CPA to suppress testosterone production to within the pre-menopausal female range (based on clinical blood assays for the ‘normal’ female range (Clark et al., 2019) this study targeted 0.5 and 1.5 nmol/L) in trans people with functioning testosterone producing gonads? and (3) can alternate days (or 3 days a week) or twice weekly CPA be effective? Findings of this study will help to inform the development of an evidence-based titration protocol to guide physicians who prescribe CPA as a component of GAHT.

Methods

Participant recruitment

Participants were recruited across six study sites, five of which were primary care facilities (some specializing in LGBTQ + wellbeing and sexual and reproductive health), and one sexual health clinic at a tertiary hospital. Participants were eligible for the study if they were a) aged 18 years or above, b) seeking full dose feminizing hormone treatment, and c) requesting treatment with CPA as part of their regimen. Participants were recruited into the study by the physician responsible for the management of their GAHT with the aim of reducing their CPA level while maintaining target testosterone ranges. Before enrollment, participants provided their written informed consent and were made aware that declining participation would not interrupt their access to CPA. Recruitment commenced in June 2020 and concluded in October 2022. At study conceptualization, the investigators did not have access to an accurate sample frame to assist with estimating a defined target sample size. A target sample of 120 to 350 participants was calculated by investigators based on estimates of the existing client loads at each of the relevant Australian Medical Clinics study sites provided by the study site investigators. However, the COVID-19 pandemic, along with staff changes and clinic logistics caused significant disruption to clinical services and reduced study site investigators’ capacity to enroll participants into the study and complete the protocol. An amendment to study methodologies was therefore developed in consultation with the site investigators and ethical approval sought to also include retrospective data collection at study sites where the CPA titration protocol was being used as standard practice prior to the study commencement. Before the retrospective data were accessed from the clinical records, a participant information and written informed consent for Retrospective Data Collection was obtained from participants.

Titration protocol and procedure

Upon entry, baseline levels of testosterone, estrogen, and current CPA level were recorded. Administration of CPA was defined using a titration protocol, classing CPA dosage into 5 titration levels (outlined in Table 1 and Figure 1). Patients who were treatment naïve (received no prior dosage of CPA at baseline) were automatically assigned to protocol level 3 (12.5 mg CPA daily or 25 mg alternate days) and were also established on estrogen therapy. Other participants who were previously on CPA before joining the study were assigned to the protocol level that matched their current dose. After the initial visit and commencement, participants had three clinical visits (a minimum of six weeks post dose change to allow changes in pituitary stimulation to achieve the target testosterone range (0.5-1.5 nmol/L). A target testosterone range of 0.5-1.5 nmol/L was determined for the protocol based on the Endocrine Society guidelines for feminization indicating serum testosterone levels should be <50 ng/dL (equivalent to approximately 1.7 nmol/L) (Hembree et al., 2017), along with clinician experience and patient preference for testosterone range to be below the upper female limit. At the time of each visit if participants were above or below the target testosterone ranges, CPA level was adjusted (increased and decreased, respectively) to achieve target testosterone range. Participants who achieved the target testosterone range were deemed to have fulfilled the protocol. A final review was conducted with all participants a minimum of one year after initial recruitment to assess long-term protocol success in testosterone suppression. Data entered retrospectively followed the same number of data entry points as prospective data collection.

Table 1. Overview of the titration protocol used in this study and protocol for level adjustments based on testosterone range.

Protocol levels

Level 4 – 25 mg daily

Level 3 − 12.5 mg daily / 25 alternate days

Level 2 − 12.5 mg three times weekly / alternate days

Level 1 − 12.5 mg cyproterone twice a week

Level 0 – Using cyproterone at an alternative / lower dose

Protocol for CPA level changes based on testosterone level

if T < 0.5 nmol/L - reduce dose by one level

if T > 1.5 nmol/L - increase dose by one level

Notes. treatment naïve patients were initiated on level 3.

Data was recorded using the REDCap electronic data capture tool hosted at The University of Queensland (Harris et al., 2019; Harris et al., 2009).

Data analytical procedure

Descriptive analysis was conducted using Stata Statistical Software: Release 17 (StataCorp, 2021), to investigate various factors of interest that pertained to the aims of the study including CPA levels, testosterone ranges, estrogen serum concentrations and estrogen dose. A multilevel model was used to explore the effect of CPA on testosterone at each time point while accounting for serum estrogen.

Results

A total of 80 participants were entered into the study. Six participants were removed as no CPA was administered and no data had been entered across all categories/timepoints after enrollment, leaving a total of 74 participants from across three study sites—Western Australian, Queensland and New South Wales. All but one participant identified as male at birth (73, 98.7%), and the majority (71, 96.0%) reported their preferred gender as female at the time of enrollment. Most participants were recruited from Queensland (QLD) (42, 56.8%) and Western Australian (WA) (26, 35.1%) sites and were aged between 21-25 (29, 39.2%). Most participants reported taking estrogen at baseline (51, 68.9%), administered via oral estradiol valerate (36, 48.7%) and topical estradiol (15, 20.3%). Only 1 participant was taking oral progesterone at baseline. The majority of participants were on CPA at baseline (46, 62.2%), 29.7% (22) were on level 4 (25 mg daily), 27.0% (20) on level 3 (12.5 mg daily/25 alternate days) and 5.4% (4) were on level 0 (alternative/lower dosage). Just over a third (27, 36.5%) were treatment-naïve at baseline. Participant demographic information it provided in Table 2.

Table 2. Participant demographics.

	n = 80	%
Age
18 -20	9	12.2
21-25	29	39.2
26-30	16	21.6
31-35	9	12.2
36 - 40	6	8.1
40+	5	6.8
Recruitment site location
Queensland	42	56.8
Western Australia	26	35.1
New South Wales	6	8.1
Gender at birth
Male	73	98.7
Female	1	1.3
Preferred gender
Female	71	96.0
Male	1	1.3
Other	2	2.7
Estrogen baseline
Yes	51	68.9
No	22	29.7
Missing	1	1.4
Estrogen baseline route of administration
Oral estradiol valerate	36	48.7
Topical estradiol	15	20.3
Missing	0	0.0
Estrogen endpoint
Yes	49	66.2
No	0	0.0
Missing	25	33.8
Estrogen endpoint route of administration
Oral estradiol valerate	14	18.9
Topical estradiol	14	18.9
Hormone implant	21	28.4
Missing	25	33.8
Progesterone baseline
No	72	97.3
Yes	1	1.4
Missing	1	1.4
Progesterone baseline route of administration
Oral	1	1.4
missing/no response	73	98.7
Progesterone endpoint
No	33	44.6
Yes	16	21.6
Missing	25	33.8
Progesterone baseline route of administration
Oral	15	20.9
Oral/rectal	1	1.4
Missing/no response	58	78.4
Baseline CPA^a
Level 1 − 12.5 mg cyproterone twice week	0	0.0
Level 2 − 12.5 mg three times weekly / alertnate days	0	0.0
Level 3 − 12.5 mg daily / 25 alternate days	20	27.0
Level 4 - 25 mg daily	22	29.7
Treatment naïve (no current dose)	27	36.5
Level 0 - Other (Currently on an alternate dose)	4	5.4
Missing	1	1.4
Testosterone levels at baseline
⋜ 0.5 nmol/L	4	5.4
0.5-1.5	6	8.1
⋜ 1.5 nmol/L	55	74.3
Missing	9	12.2

^a CPA: Cyproterone acetate.

Table 3. Number of participants within testosterone range (0.5-1.5 nmol/L) at each protocol time point (Tn) of those that had data recorded.

	T0^a		T1		T2		T3		T4
	n	%		%	n	%	n	%	n	%
CPA^b dose
Level 1 − 12.5 mg cyproterone twice a week	0	0	1	1.4	7	10.9	13	25.0	19	38.0
Level 2 − 12.5 mg three times weekly/alternate days	0	0	8	10.8	22	34.4	14	26.9	6	12.0
Level 3 − 12.5 mg daily/25 alternate days	21	27.3	51	68.9	31	48.4	19	36.5	17	34.0
Level 4 - 25 mg daily	24	31.2	12	15.2	3	4.7	3	5.8	2	4.0
Level 0 – Using cyproterone at an alternative/lower dose	5	6.5	2	2.7	1	1.6	3	5.8	2	4.0
Treatment naïve^c – no current dose	27	35.1	0	0	0	0	0	0	0	0
Treatment ceased	0	0	1	1.4	1	1.6	1	1.9	4	8.0
Total (n) completing each time point	77	97.5	74	93.7	64	81.0	52	65.8	50	63.3
Missing^d	2	2.5	4	5.1	14	17.7	26	32.9	29	36.7
Total initiating protocol	79	100	79	100	79	100	79	100	79	100
Target testosterone range
< 0.5 nmol/L	4	6.2	22	30.6	17	26.6	13	25.5	10	21.7
0.5-1.5 nmol/L	6	9.2	47	65.3	43	67.2	36	70.6	34	73.9
> 1.5 nmol/L	55	84.6	3	4.2	4	6.3	2	3.9	2	4.4
Total recorded	65	100	72	100	64	100	51	100	46	100
Missing	9		2		10		27		28
Testosterone and estrogen serum levels and dose (range)
Mean testosterone (nmol/L)	16.4	(0.3-33.0)	0.7	(0.3-17.6)	0.76	(0.3-10.8)	0.8	(0.3-5.5)	0.9	(0.3-8.5)
Mean estrogen dose (mg)	2.8	(2-8)	4.1	(1-10)	4.5	(1-10)	3.8	(2-8)	3.0	(2-10)
Mean serum estrogen (pmol/L)	220.9	(98-937)	284.8	(69-937)	331.6	(37-4280)	415.8	(57-1430)	663.9	(54-2080)

^aTime points (Baseline/T1/T2/T3/endpoint) are a minimum of 6 wk since previous visit/timepoint.

^bCPA: cyproterone acetate.

^ctreatment naïve patients were initiated onto level 3 of the protocol.

^dMissing % is calculated from total cohort (n = 74).

CPA titration

CPA levels were tracked across 5 clinical visits (including baseline (T0) and protocol endpoint (T4)). Almost all participants who completed the protocol (91.3.0%, 42/46) recorded their CPA levels as level 3 (12.5 mg daily/25 alternate days) or lower, with 69.0% (29/42) of these being able to achieve the target T-range. Of those that completed, 41.3% (19/46) were able to achieve the lowest CPA level (12.5 mg cyproterone twice week) with 57.9% (11/19) being able to achieve the target T-range.

There was a high rate of loss to follow up across the duration of the study with just over half (62.2%, 46) completing and 4 (5.4%) having ceased treatment at the protocol endpoint—believed to be in part due to the impacts of COVID-19 occurring during data collection along with the natural loss of patient follow up/attendance experienced by clinicians (e.g. patients moving/finding alternative clinical care).

Testosterone and estrogen levels

Most participants who had testosterone level recorded at baseline were recorded as above 1.5 nmol/L (84.6%, 55/65). By time point one (T1) 65.3% (47/72) of those with testosterone levels recorded were within the target range, and 73.9% (34/46) were able to achieve target T-range by the protocol’s endpoint. Mean testosterone reduced throughout the protocol from 16.4 pmol/L at T0 to between 1.7 and 1.9 between T1-T4. Mean estrogen dose fluctuated throughout the protocol from 2.8 mg/L (T0) to 4.5 mg/L (T2), and mean estrogen serum level increased from 220.8 pmol/L at T0 to 663.9 pmol/L at T4 (Table 4).

Table 4. Estimates of testosterone at each timepoint based on cyproterone acetate use and estrogen.

	Model 1			Model 2
	Coeff	SE	P-value	Coeff	SE	P-value
Intercept (T0)
T1^a	−13.944	0.724	<0.001	−5.879	0.739	<0.001
T2	−13.974	0.746	<0.001	−5.734	0.749	<0.001
T3	−14.228	0.795	<0.001	−5.997	0.769	<0.001
T4	−14.166	0.818	<0.001	−5.851	0.787	<0.001
Estrogen serology				−0.001	0.0005	0.236

^aTime points (T0 = baseline; T1-T3, T4 = endpoint) – time points are a minimum of 6 wk apart.

A multilevel model was used to investigate the effect of estrogen on testosterone throughout the protocol. Model 1 indicates that overall, among people receiving CPA there is a large initial drop in testosterone between T0 (baseline) and T1 (Coeff −13.944, p < 0.001), and then followed by a plateau between T1 and T4 (p < 0.001). When adjusting for estrogen in model 2 the magnitude of this drop reduces (Coeff −5.879, p < 0.001), however estrogen is not significant in this model (Coeff −0.001, p = 0.236). (Table 4).

Discussion

This uncontrolled intervention study explored a CPA titration protocol designed to determine the lowest biochemically effective dosage of CPA administered as part of GAHT. The study findings showed that for some patients, CPA doses as low as 12.5 mg on alternate days or less can successfully reduce testosterone to pre-menopausal ranges whilst ensuring testosterone was not over-suppressed. This indicates that lower dosing of CPA may be a valuable treatment option to mitigate the potential side-effects of higher doses of CPA.

Due to the potency of CPA and its associated (but rare) side-effects (Bergoglio et al., 2013; Burinkul et al., 2021; Gazzeri et al., 2007; Kim et al., 2014; Knight & McDonald, 2013; Ter Wengel et al., 2016; Thole et al., 2004), reductions in the clinically effective dosage of CPA are important to minimize the potential for adverse effects. Our study found that doses of CPA lower than the standard dose (12.5 mg CPA daily and/or 25 mg alternate days) were achievable for suppression of testosterone. Several studies have supported this finding that a lower dosage (10 mg CPA daily) is effective in testosterone reduction in individuals undergoing hormone feminization (Even Zohar et al., 2021; Kuijpers et al., 2021). While not all individuals within our study were able to titrate down CPA dosages, almost a quarter of participants who completed the protocol were achieving target T-ranges on 12.5 mg CPA twice weekly (equivalent to 3.5 mg/daily). To our knowledge ours is the first study to demonstrate that doses lower than 10 mg/daily as well as alternate days or twice weekly CPA are clinically effective in maintaining testosterone reduction within target ranges. This provides important clinical implications for the low- and alternate-day-dosing of CPA for trans individuals undergoing feminization to reduce the risk of dose-dependent side effects (e.g. meningioma) (Gazzeri et al., 2007; Gil et al., 2011; Nota et al., 2018; Weill et al., 2021). Further research is required to support this finding, however clinical practice and guidelines should consider reductions in CPA dose based on monitored testosterone levels.

Distinct from previous clinical studies investigating single low dose CPA, our protocol allowed for successive dose reduction of CPA. Our protocol followed a stepwise reduction in CPA dosage based on biochemical markers (e.g. over or under suppression of testosterone) to achieve a target testosterone range. This method allowed for dose changes in CPA to be administered based on biochemical markers of testosterone that ensured that over-suppression of testosterone did not occur. Previous investigations of CPA dosage have focused on set dosing of CPA to determine low dose efficacy (Even Zohar et al., 2021; Kuijpers et al., 2021). However, our study demonstrated that individualized treatment of patients allowed for CPA dose to be adjusted based on clinical responses (testosterone ranges) to CPA. This might suggest that future clinical practice should consider the use of a stepwise approach to CPA dosing to ensure that target testosterone ranges are achieved. This method would ensure that CPA dosage is adjusted based on individual responses that could occur due to changes or declines in T levels associated with age and/or other genetic/lifestyle factors (Bhasin et al., 2010; Johnson et al., 2013; Seidman, 2007).

Over-suppression of testosterone (below 0.5 nmol/L) was observed among some patients in our study, resulting in clinicians adjusting CPA dosage to restore target ranges (0.5-1.5 nmol/L). This provides important implications for clinical practice to reduce the impacts of over-suppression of testosterone (reductions in energy levels and libido, and heightened risk of cardiovascular disease) that can result from CPA use (Halpern & Brannigan, 2019; Rako, 2000; Spry et al., 2009). Our protocol provided a good structure for clinical practice to ensure that suppression of testosterone is maintained without unmonitored over-suppression. Clinicians providing GAHT should ensure comprehensive medication management is based on both clinical response and regular testing of biochemical markers (monitored through routine blood tests associated with GAHT), to ensure over-suppression of testosterone does not occur. As well, the ability to titrate CPA dosing against testosterone levels to control over-suppression highlights a unique advantage of CPA against other commonly used anti-androgens, such as spironolactone.

Estradiol is the most commonly prescribed feminizing hormone in Australia, commonly prescribe alongside anti androgens such as CPA (Cundill, 2020). Estradiol is known to have a suppressing effect on testosterone in a dose-dependent manner (Leinung et al., 2018). Our study found that for individuals taking the CPA in combination with estradiol, there was a significant reduction in testosterone, when accounting for estrogen serum concentrations. Similarly a 2019 Australian study investigating the effects of CPA, estradiol and spironolactone found that a CPA estradiol combination had the most significant impact on testosterone when controlling for estrogen (Angus et al., 2019). This indicates that the effect of estrogen may not be playing a significant role in testosterone reduction when taken in combination with CPA.

The use of this protocol has verified that there is potential for CPA dosing to be reduced below current clinical standard dosing, and lower than previous studies have demonstrated, thus providing important benefits for the reduction in CPA dosing and its associated side effects (Bergoglio et al., 2013; Burinkul et al., 2021; Gazzeri et al., 2007; Kim et al., 2014; Knight & McDonald, 2013; Ter Wengel et al., 2016; Thole et al., 2004). However, as reported by our clinicians, difficulties in medication and treatment regimens can arise due to transient patients and attendance across different services and providers. Therefore, our protocol provides structured guidance for the administration of CPA to individual patients through routine monitoring of biochemical markers for testosterone allowing for adjustment and stepwise reductions of CPA dosage according to patient responses. Clinical guidance provided by our protocol for the titration of CPA dosing provides a useful regimen for clinical practice to not only reduce CPA dosage and its longer-term effects but ensure that target testosterone ranges are achieved without over suppression that can occur at higher CPA doses.

Strengths and limitations

This is the first study to our knowledge that investigates lowest CPA dosage as well as alternate day dosing. This study builds upon previous studies on lowering doses of CPA, thereby providing important implications for clinical practice. The sample size and high dropout rate of participants limited our ability to investigate the statistical significance of our findings, however descriptive analyses were conducted to investigate CPA titration, estrogen and testosterone. Participant dropout reason was not captured, therefore allowing limited insight into potential side effects resulting in discontinuation of treatment. Due to lack of qualitative data captured we are unable to determine the psychological effects of low dosage CPA on participants, for example mood changes and physical effects experienced from taking CPA. Therefore, whilst we were able to explore biochemical suppression, the impact and side effects experienced alongside this titration are not reported. These limitations should be taken into consideration when interpreting the study’s findings.

Conclusion

This study provided clinical evidence that lower and alternate-day dosing CPA can be achieved in individuals undergoing feminizing GAHT. While lower doses were achieved this was not the case for all participants, indicating the need for clinical practice to be tailored to the biochemical (and clinical) responses of the individuals. However, this study provided promising evidence for reductions in CPA dosing to reduce the impacts of CPA-related side effects and improve the outcomes and experiences of individuals undergoing GAHT.

Ethical approval

Ethical approval was provided by the Royal Brisbane and Women’s Hospital Human Research Ethics Committee (HREC/2019/QRBW/59298).

Acknowledgments

We wish to thank Mattea Lazarou for her contribution to the development and early administration of this study and Dr Rebecca Overbury for their support in recruiting participants into this study. We would also like to acknowledge and thank the study participants for their valuable contributions as well as the study site investigators and staff who assisted with recruitment and data collection.

Disclosure statement

The authors have no conflicts of interest to declare.

Data availability statement

The data that support this study cannot be publicly shared due to ethical or privacy reasons.

Additional information

Funding

This research was supported by the Sexual Health Research Fund, an initiative of the Sexual Health Ministerial Advisory Committee, funded by Queensland Health. It is administered by ASHM.