Vaginal Prolapse, Pelvic Floor Function, and Related Symptoms 16 Years After Sex Reassignment Surgery in Transsexuals

     Cross sectional study of 52 MTF patients assessing for prolapse and related bladder, bowel and sexual problems found 3.8% of patients having prolapse warranting surgical repair, 47% with voiding difficulties, and 75% reporting that sexual complaints in some way interfered with their enjoyment of life.  (1)

     Pelvic organ prolapse affects 50% of non-transsexual parous women over age 50, though not all women with clinical signs of prolapse are symptomatic.  The authors aimed to assess the prevalence of pelvic organ prolapse in a cross sectional study of post-vaginoplasty MTF transsexual patients with a median age of 57 (range 39-69 years) under care at a single Swiss tertiary referral gynecology & endocrinology service.  The medial postoperative time was 16 years (range 13-29 years).  49 patients had undergone scrotal inversion and 3 patients had undergone sigmoideocolpoplasty at 14 different surgical centers distributed between Switzerland, the UK, France, the US and Thailand.  Objective measurement by a single examiner using the International Continence Society - Pelvic Organ Prolapse scoring (ICS-POP) and subjective symptom survey using the Sheffield Pelvic Organ Prolapse Quality-of-Life Questionnaire (SPS-Q) were conducted.

     7.5% of patients were found on exam to have an ICS-POP score greater than 2, with 3.8% of patients requiring surgical repair.  47% of patients reported voiding difficulties, 24.6% reported urgency, 17% urge incontinence, and 23% stress incontinence.  With respect to sexual satisfaction, 22.6% reported "never" and 26.4% reported "occasionally".  The paper includes a discussion of various anatomical considerations in pelvic surgery on transsexuals and also looked at outcomes in 3 FTM patients.

Comments:

     This paper is useful in reminding us that vaginoplasty is not a risk-free procedure, and that a non-trivial percentage of patients will experience bothersome urinary and sexual symptoms that can impact quality of life.  Primary care providers and surgeons should discuss known and unknown risks and percentages during the informed consent process prior to surgery.  These data are also useful in the ongoing development of government policies which allow changing legal documents to reflect the affirmed gender without requiring surgical intervention;  As more data emerge showing that surgery can be associated with substantial morbidity, the justification of surgery as a requirement for changing documents becomes weaker.

     The paper has several strengths and several weaknesses.  Using a single examiner eliminates inter-examiner reliability issues with respect to ICS-POP scoring.  At the same time, decision to perform pelvic surgical repair in cases of prolapse is more often guided by patient symptomatology and response to conservative treatment.  The study sample was rather large, but skewed towards an older population with an average age of 57.  The study population also represented an all-comer population from surgeons in a range of countries, but individual outcomes by surgeon or country were not reported.  Being a tertiary referral center, referral bias may have caused a higher prevalence of pathology in the study population.  The ICS-POP and SPS-Q scales have not been validated in transsexuals, and given the discussed anatomical differences may not be applicable or clinically relevant.  Comparisons are made to the prevalence of pelvic symptoms in parous non-transsexual women;  Weather or not this comparison is applicable vs. comparisons between groups of transsexual women by age or surgical technique, or comparison with pre- or non-op transsexual women are subjects to ponder.

References:

1) Kuhn A, Santi A, Birkhäuser M. Vaginal prolapse, pelvic floor function, and related symptoms 16 years after sex reassignment surgery in transsexuals. Fertil. Steril. 2011 Jun;95(7):2379–82.

Selective Estrogen Receptor Modulators (SERMs) for Uterine Leiomyomas (Cochrane Review)

     Cochrane Review of limited studies on the use of SERMs for uterine fibroid symptoms shows no clear evidence supporting this practice. (1)

     Uterine fibroids are known to respond to hormonal factors such as estrogens and progesterone.  Some hypothesize that a reduction in estrogen levels could improve fibroid symptomatology.  SERMS are mixed estrogen agonists/antagonists, and the SERM raloxifene specifically blocks estrogen action in breast and uterine tissue while stimulating receptors in bone and maintaining estrogenic effect on lipids.

     This Cochrane Review sought randomized controlled trials (RCT's) of women aged 18 to 45 with a diagnosis of uterine fibroids that included a raloxifene treatment arm.   Only three studies were identified, all of which had methodological limitations and data quality issues.  Adverse effects were not tracked by any of the studies.  The authors concluded that there exists insufficient evidence to support the use of SERMs in the management of uterine fibroids.


Comment:

     Transgender men receiving testosterone replacement who have not undergone oopherectomy may or may not have complete suppression of the hypothalamic-pituitary axis (HPA).  This combined with peripheral aromitization of exogenous testosterone may lead to persistantly elevated estrogen levels.  Unlike in transgender women, where testosterone blockade is central to hormonal reassignment regimens, cross gender HRT in trans men has not historically included blockers or other agents to manipulate estrogen levels.

     While most trans men do well clinically with testosterone only, a minority may present with a constellation of symptoms including abdominal or pelvic cramping, vaginal spotting, and bleeding or failed induction of amenorrhea.  Anecdotal clinician reports suggest that these patients tend to have serum estrogen levels above the normal male range, raising the question of weather or not estrogen level manipulation might improve these symptoms.

     The use of SERMs for uterine fibroids is essentially attempting to acheive similar outcomes of reduced estrogenic activity on the uterus while protecting bone health.  Bone health outcomes in trans men is an area of debate and limited evidence;  In theory, SERMs could offer relief to those trans men experiencing symptoms believed to be related to estrogen excess while reducing risks to bone health that might be seen with aromatase inhibitors or oopherectomy.   The increased risks of stroke, thromboembolic disease and hot flashes seen with SERMs in women may be mitigated in trans men by the presence of exogenous testosterone.

     This inconclusive Cochrane Review of limited quality studies does nonetheless bring to light the possible role of SERMs in the manipulation of estrogen levels and how this role might be applicable in the treatment of trans men.   Further study in this area as well as the use of aromatase inhibitors would be useful to assess their role in trans men on testosterone.

References:

1) Wu T, Chen X, Xie L. Selective estrogen receptor modulators (SERMs) for uterine leiomyomas. Cochrane Database Syst Rev. 2007;(4):CD005287. 

The Effects of Hormonal Gender Affirmation Treatment on Mental Health in Female-to-Male Transsexuals

     Results of an online, self-reported survey of a population of predominantly young, white, and educated female-to-male transsexuals demonstrated improved quality of life and reduced prevalence of mood disorders with the administration of testosterone. (1)

     Little data exist on the effects of cross gender HRT (cHRT) alone with respect to satisfaction and quality of life outcomes or the effect of cHRT on the prevalence of mood disorders in transgender persons.  Much of the existing data on these measures focuses on surgical interventions.  The authors distributed a self-reported survey to female-to-male (FTM) transsexuals via online discussion groups, measuring symptoms of depression, anxiety and stress as well as current perceived social support and health-related quality of life. The authors hypothesized that cHRT in FTM transsexuals reduced reported symptoms of depression, anxiety and stress and improved perceived social support and health-related quality of life.

     A total of 448 responses were collected, of which 369 were complete and met the minimum age requirement of 18 years.  The sample had an average age of 28, was predominantly white (76%), and educated (88% at least some college),  with 85% living in the US and 50% reporting sexual attraction to both men and women.  Sixty-six percent of respondents were on cHRT, and 41% of respondents had undergone male chest reconstruction (all but 7 of whom were also on cHRT).

     FTM transsexuals receiving cHRT reported statistically significantly lower levels of depression, anxiety and stress and higher levels of perceived social support and health-related quality of life.  Interestingly FTM transsexuals not on cHRT in this sample reported depression, anxiety, stress close to the control range.  Both groups reported lower than average perceived social support.  Both groups reported health-related quality of life higher than the control average.

Comment:

     This groundbreaking study looks at cHRT as a specific intervention with respect to mental health outcomes and quality of life measures.  Most outcome-based research on transgender populations have been focused on surgical interventions.  Looking at cHRT alone as an intervention that improves quality of life and mental health outcomes has significant implications for healthcare systems that offer limited (or no) access to more expensive surgical procedures which require additional resources and highly skilled surgeons, as well as for transgender persons who may simply not want to pursue genital surgery for a variety of reasons.

     One additional result of note is that 50% of respondents reported a sexual attraction to both men and women, further supporting the growing awareness of diversity of sexual orientations in transgender persons.

     One limitation mentioned by the authors is that the use of a psychological screening process to gain access to cHRT in some cases may color the differences between the cHRT and non-cHRT populations.  In fact, transsexuals with more severe mood symptoms may be more likely to be denied cHRT; Data on the reason(s) that the non-cHRT users were in fact not on cHRT would be helpful.  Additionally, nearly 62% of the cHRT users had undergone chest reconstruction while only 6% of the non-cHRT users had done so;  A subgroup analysis around this variable would have been helpful in determining any confounding of the results from this high prevalence of chest surgery in the study sample, as well as evaluating any incremental effects between cHRT alone and cHRT + chest surgery.  Nevertheless, chest reconstruction in its most rudimentary form is a much less painful, costly and specialized procedure than phalloplasty and as such these data are still quite relevant in the context of resources, availability and individual patient desires.

     It is interesting that respondents reported higher perceived social support on cHRT;  Was this simply an issue of perception, or was the actual provided support higher once on cHRT?  Additional study would be useful to determine the role of the former and the latter and to determine the community and societal factors driving this difference.   It is also interesting that FTM transsexuals not on cHRT reported levels of mood disorders not far from general population controls and that across all respondents reported health-related quality of life was higher than average.   This along with the somewhat homogeneous, white, educated sample limits the applicability of this study across other demographics;  Nonetheless it is a welcome addition to the nascent field of research on transgender persons undergoing cHRT alone and will hopefully lead to more study in this area.

References:

1) Colton Meier SL, Fitzgerald KM, Pardo ST, Babcock J. The Effects of Hormonal Gender Affirmation Treatment on Mental Health in Female-to-Male Transsexuals. Journal of Gay & Lesbian Mental Health. 2011 Jul;15(3):281-299. 

Microflora of the Penile Skin-Lined Neovagina of Transsexual Women

     In a study of the penile-inversion neovaginal microbiome of 50 transsexual women,  vaginal irritation and discharge was not correlated with the presence or absence of leukocytes or specific organisms on gram stain.  No cases of candidal colonization were identified, and only one woman had lactobacilli. (1)

     Transsexual women often present with a variety of vaginal symptoms after penile-inversion vaginoplasty.  The authors aimed to identify colonizing flora of the neovagina, and determine if any correlation existed between vaginal cleansing habits, specific flora or the presence of leukocytes and symptoms of irritation or discharge.  They also aimed to evaluate any correlation between sexual orientation (i.e. presence or absence of receptive penetrative sex with a penis) and presence of particular microbiologic species.

     50 post-vaginoplasty transsexual women (mean time since surgery: 6.3 yrs) were studied through a combination of pelvic examination, gram stain and culture/PCR, and self-report survey.  Almost all were on estrogen HRT (94%),  44% were heterosexual, 22% homosexual, 28% bisexual and 6% asexual.  Regular episodes of vaginal irritation occurred in 22% of the women and 18% experienced frequent dysuria.  Only 34 women answered questions about foul smelling discharge;  Of these, 23.5% had frequent foul smelling discharge.   No correlation was found between vaginal rinsing habits and vaginal pH or vaginal discharge, and no correlation was found between vaginal pH and complaints of irritation or malodorous discharge.  No correlation was found between the presence of leukocytes and reported malodorous discharge. 

     Mean vaginal pH was found to be 5.88.  On exam, clinicians reported a foul smelling discharge in “most patients”.  Microbiological studies revealed a mixed vaginal flora with typical skin and intestinal organisms.   Lactobacilli were found in only one woman, and candida were notably absent from all women.  Notably, colonization with E. faecalis was correlated with both heterosexual orientation and regular receptive coitus with a male partner.  Mobiluncus (a genus typically resistant to metronidazole) was found in higher numbers than in natal vaginal flora.  All participants were negative for Chlamydia and gonorrhea.  Twelve novel, untypable species were identified.  No strong correlation was found for any specific flora species and symptoms.

     The authors conclude that they are unable to explain the high rates of vaginal discharge and irritation in transsexual women through microbiologic analysis or analysis of vaginal rinsing habits. 

Comment: 

     This article highlights the fact that postoperative symptoms of irritation, odor, discharge, and dysuria are common complaints in transsexual women, even years after surgery.  It also reminds providers to take a different approach to penile-inversion neovaginas than they would for natal vaginas in the setting of vaginal complaints.  Also of interest is that the neovagina is colonized (not surprisingly) with a variety of skin and intestinal flora, and in heterosexual transsexual women active in receptive coitus is more likely to be colonized with the UTI-causing coliform E. faecalis. 

     No correlations with symptoms were found between symptoms and cleansing habits, pH, a particular microbial species, or the presence of leukocytes.  Only one woman was colonized with lactobacilli, and no candida was found.  Hopefully this will help lay to rest the notions that neovaginas are (or should become) colonized with a usual vaginal microbiome, that lactobacilli are important for neovaginal health, that neovaginal candidiasis is a common entity, and that pH effects microbial outcomes in neovaginal health. 

     The authors are unable to draw any conclusions on neovaginal symptomatology from a microbial perspective; It is likely that while colonization occurs, most neovaginal symptoms are not infectious in nature and instead relate to the constant production of sebum, sweat, and cellular and keratin debris that occurs in a skin-lined vagina.  Also likely to contribute is the presence of semen, lubricating gels and other foreign substances and the constant “skin-on-skin” irritation which may occur.  Treating neovaginal symptoms with antimicrobials is likely only treating colonization.  It is curious that cleansing habits did not improve or worsen symptoms.  More outcome-based research is needed to explore risk factors and curative interventions for neovaginal symptomatology.

Several additional points of interest in this paper:
- The range of reported sexualities in the study population supports the notion of diversity of sexual orientations among transsexual women

- A metronidazole-resistant microorganism was commonly found in neovaginas, suggesting that clindamycin should be used if one does decide to treat with antibiotics

- Heterosexual transsexual women are at higher risk of E. faecalis colonization.  Weather specific recommendations for preventive measures against UTI should be given to tramssexual women, and what measures should be taken are areas for future study.

- The fact that none of the 50 women were positive for gonorrhea or Chlamydia suggests that the neovagina itself is resistant to infection with these organisms;  Providers may consider obtaining swabs for these organisms from the urethral meatus for a higher yield.  It also may simply suggest that there are populations of transsexual women who have a low incidence of these (and perhaps other) STI’s.

References:

1) Weyers S, Verstraelen H, Gerris J, Monstrey S, Santiago G dos SL, Saerens B, et al. Microflora of the penile skin-lined neovagina of transsexual women. BMC Microbiol. 2009;9:102. 

Incidence of Thrombophilia and Venous Thrombosis in Transsexuals Under Cross-Sex Hormone Therapy

     Retrospective cohort study of 162 MTF patients on transdermal estradiol + cyproterone acetate with an 8% prevalence of baseline thrombophilic conditions showed no incidents of venous thromboembolism over an average 49.6 months. (1)

     Venous thromboembolism (VTE) is a common concern for providers providing cross gender hormone therapy (cHRT) for male-to-female (MTF) transgender persons.  Additional concern may exist for patients with pre-existing prothrombotic mutations, and the question arises as to weather or not it is important to pre-screen MTF persons for hypercoagulability prior to initiation of cHRT.

     Researchers conducted a retrospective review of outcomes in a cohort of 162 MTF women who had a baseline prevalence of 8% (13/162) prothrombotic mutations, which is consistant with the baseline prevalence in non-transgender caucasian persons.  All 13 patients exhibited activated protein C (aPC) resistance and four were smokers.  No cases of antithrombin III or protein C deficiency were found the study population.  Only one patient (a smoker) was on anticoagulation therapy.  161/162 patients received either transdermal estradiol monotherapy (if post-op) or transdermal estradiol + cyproterone acetate + finasteride (if pre-op).  One patient with multiple cardiovascular risk factors and aPC resistance (not on anticoagulation) was given cyproterone acetate monotherapy.  60/162 patients had reported prior self-directed cHRT use, all had been off cHRT for a minimum of 4 weeks prior to treatment at the study site.

     Over a mean duration of 49.6 months on cHRT (range 12-135 months), no incidents of VTE were observed in the study cohort.  The expected incidence of VTE in 0.43/18 patients with a prothrombotic mutation did not differ significantly from the observed incidence of 0/18.  The authors concluded that cHRT in transgender persons with a prothrombotic mutation is safe, and that routine pre-cHRT screening for prothrombotic mutations is not recommended if there is no family or personal history of VTE.

Comment:

     Venous thromboembolism is a commonly feared outcome of cross gender hormone therapy, but a growing body of recent evidence has shown that the use of transdermal estradiol (or oral estradiol as opposed to conjugated equine or synthetic estrogens) minimizes this risk.  The authors chose to look at the risk of VTE in a cohort of MTF women who were pre-screened for the presence of a prothrombotic mutation.  None of the women, with or without a mutation had a VTE during the study period of an average 49.6 months.  Since most incidents of VTE occur in the first year of HRT in non-transgender contexts, their conclusions that cHRT with respect to thrombophilia is safe seems reasonable.  This study should help reassure the clinician that the use of safe cHRT such as transdermal estradiol minimizes VTE risk in the general population and in those with minor prothrombotic mutations such as aPC resistance / factor V Leiden.

     Shortcomings include the relatively small number of patients, retrospective nature and the lack of any patients in the cohort with more serious prothrombotic mutations such as antithrombin III or protein C deficiency.

     Of note, the study also looked at an FTM cohort and found similar results.  While the authors cite several basic science articles suggesting testosterone increase thrombotic risk in lab animals, this is not congruent with publications in trauma research which suggest that testosterone leads to a hypocoaguable state. (2)

References:

1) Ott J, Kaufmann U, Bentz E-K, Huber JC, Tempfer CB; Incidence of Thrombophilia and Venous Thrombosis in Transsexuals Under Cross-Sex Hormone Therapy; Fertil Steril 2010;93:1267-72

2) Gee AC, Sawai RS, Differding J, Muller P, Underwood S, Schreiber MA; The Influence of Sex Hormones on Coagulation and Inflammation in the Trauma Patient; Shock 2008;29:334-41