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.