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A journal club style critical review of current publications in evidence-based transgender medical care.

Friday, November 18, 2011

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.


     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.


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

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