Perioperative Management of Estrogen HRT in Transgender Patients
Current Clinical Guidelines and Recommendations
WPATH Standards of Care: The World Professional Association for Transgender Health (WPATH) now recommends continuing estrogen therapy in the perioperative period for transgender women, unless there are specific contraindications[1]. This shift in guidance was driven by emerging evidence that maintaining estrogen through surgery does not appreciably increase perioperative thromboembolism risk, while stopping it can cause significant withdrawal symptoms (e.g. hot flashes, mood changes) and even exacerbate gender dysphoria[1][2]. In fact, explanatory language was added to the latest WPATH Standards of Care emphasizing that current data do not support suspending hormone therapy before surgery[2]. The priority is to avoid the psychological and physiologic stress of abrupt estrogen withdrawal, which can include depression, anxiety, and dysphoria at a vulnerable time.
Endocrine Society Guidance: The Endocrine Society's guidelines for gender-affirming care similarly promote the use of bioidentical 17β-estradiol and advise against older estrogen formulations with higher risk profiles (such as ethinyl estradiol)[3]. They endorse standard routes of estradiol administration - oral, transdermal, or intramuscular - with a preference for safer formulations. Notably, ethinyl estradiol is specifically discouraged due to its poor safety profile and greater thrombosis risk[3]. While the Endocrine Society guideline (2017) does not explicitly mandate how to manage hormones around surgery, its emphasis on using safer estrogen formulations aligns with minimizing thrombotic risk. By using transdermal estradiol (a bioidentical form), patients inherently reduce their baseline risk of venous thromboembolism (VTE) compared to riskier oral or synthetic estrogens.
Surgical and Anesthesiology Perspectives: In the past, many surgeons routinely advised transgender women to pause estrogen 2-4 weeks prior to major surgery out of an abundance of caution regarding blood clots[4]. This practice was originally adopted by analogy to cisgender women on hormone therapy and due to historical concern with lengthy procedures (like genital affirmation surgeries) that inherently carry some VTE risk (e.g. prolonged pelvic surgery with immobility)[5]. However, surgical society guidelines have been evolving. Some perioperative protocols still vary, but authoritative reviews now conclude there is no evidence to support routine discontinuation of gender-affirming hormones before surgery[6]. For example, a 2019 systematic review in JAMA Surgery found that most data linking estrogen to clots came from older oral contraceptive studies not directly applicable to modern trans care, and it determined that broadly halting all hormone therapy pre-surgery is unwarranted[6]. Recent consensus documents in both surgery and anesthesiology literature reflect this updated view, acknowledging that continuing transdermal or modern estradiol therapy perioperatively is generally safe and avoiding estrogen withdrawal is beneficial for patient well-being[1][2]. In practice, many centers (especially those experienced in transgender health) now keep patients on their estrogen through the time of surgery, barring any high-risk contraindication.
Thrombosis Risk: Transdermal vs. Oral Estrogen
Route of administration significantly influences estrogen's impact on coagulation. Transdermal estradiol (patches, gels) has a much lower effect on clotting factors than oral estrogen does. In cisgender populations, it's well documented that oral estrogen therapy (especially non-bioidentical forms) increases VTE risk, whereas transdermal estradiol confers little to no added risk of thrombosis[7]. A large 2019 UK study in postmenopausal women, for instance, found that HRT-related clot risk was entirely driven by oral preparations (which showed a modest 1.5-2-fold risk increase depending on type), while women using transdermal estradiol had no statistically significant increase in VTE incidence compared to women not on hormones[7]. These findings echo the consensus in the gynecologic literature that oral estrogens promote a prothrombotic state (by raising factors like fibrinogen, factor VII, etc.), whereas transdermal estrogen has little or no impact on coagulation parameters[8]. Consequently, for patients who have baseline VTE risk factors (e.g. older age, smoking, prior clot history), guidelines explicitly recommend choosing transdermal 17β-estradiol or lower-risk formulations over oral estrogen[9]. WPATH's guidance reflects this: transdermal estradiol (or bioidentical oral estradiol valerate) is favored in those at higher thrombotic risk, and the use of ethinyl estradiol is not recommended in transgender care[9].
It's important to highlight that the estradiol used in transgender HRT is "bioidentical" (chemically identical to endogenous human estrogen) and, when given transdermally, leads to more physiologic hormone levels without first-pass liver metabolism. This avoids the surge in liver protein synthesis (of clotting factors) seen with oral estrogens. In short, bioidentical transdermal estradiol has a substantially safer thrombotic profile than older oral estrogen therapies. The baseline VTE risk for a healthy trans woman on transdermal estradiol is thought to be only minimally above that of a cisgender woman with natural estrogen levels or a cis woman on a similar transdermal HRT regimen[8]. Indeed, one analysis noted that transdermal postmenopausal HRT shows no significant VTE risk increase and demonstrates a "low thrombogenic profile" in users[8]. This aligns with clinical experience that maintaining physiologic-dose estradiol via skin patches does not substantially elevate clot risk - a key reason why experts feel comfortable continuing transdermal HRT even when surgery is planned.
Evidence from Recent Studies on Perioperative Estrogen
Multiple peer-reviewed studies have investigated whether continuing estrogen through surgery actually increases thrombosis rates, and the findings have been reassuring:
- Mount Sinai (2021, Kozato et al.): A large retrospective study of transgender women undergoing gender-affirming surgeries compared outcomes between those who continued estrogen therapy perioperatively and those who stopped it before surgery. In a cohort of 919 patients (over 1,800 surgeries, including 407 vaginoplasty cases), only 1 patient developed a postoperative VTE - and that patient was from the group that had discontinued estrogen[10][11]. No clots occurred in any patient who continued HRT throughout surgery[11]. The authors concluded that perioperative VTE risk was not significantly different whether estrogen was held or continued, and overall clot events were exceedingly rare in their high-volume center[12]. This study provided strong evidence that continuing 17β-estradiol (largely given transdermally or injectable in their population) does not worsen surgical clot risk in healthy trans patients, especially when standard clot prophylaxis measures are used[13]. These findings have been influential - Dr. Joshua Safer of Mount Sinai noted that this data helped inform new guidelines stating there is "no real need" to withhold estrogen for gender-affirming procedures[14][15].
- Facial Feminization Surgery (2024, Li et al.): Even in the context of very long surgeries under general anesthesia, such as facial feminization (which often involves 6-8 hours of operative time on multiple facial bone and soft tissue procedures), continuing estrogen showed no added risk. A 38-year retrospective analysis of 953 transfeminine patients undergoing facial feminization surgery (FFS) found a postoperative VTE rate of only 0.1% (1 in 953)[16], which is comparable to the baseline rate for similarly extensive surgeries in patients not on HRT. Crucially, the incidence of clots did not differ whether patients stayed on full-dose estrogen, had a dose reduction, or temporarily stopped hormones (the VTE rate was statistically the same across groups, P > 0.99)[16][17]. The authors' conclusion was unambiguous: perioperative use of feminizing HRT does not increase VTE risk in FFS, and it is reasonable to continue estrogen through the time of surgery[18]. This study specifically addressed a surgery type considered relatively lower-risk for clots and affirmed that even in these cases, stopping HRT is unnecessary.
- Systematic Reviews and Meta-Analyses: Broader reviews reinforce these individual studies. A 2018 systematic review in JAMA Surgery (Boskey et al.) examined all available evidence on exogenous hormone use and surgical risk in transgender patients. It found no convincing evidence that continuing cross-sex hormone therapy leads to worse surgical outcomes or higher VTE rates[6]. Notably, the review pointed out that the data often cited to justify holding estrogen were based on oral contraceptives or older high-dose oral estrogens, which are not the regimens typically used in transgender care today[19]. In other words, past concerns were extrapolated from dissimilar contexts. The review's takeaway was that routine discontinuation of gender-affirming hormones prior to surgery is not supported by current evidence[6]. Similarly, a 2021 meta-analysis on VTE prevalence in transfeminine people found an overall low incidence (~2% prevalence of any VTE) and noted that younger trans women (<~37 years) on estrogen for under 4-5 years had essentially negligible VTE risk[20][21]. While continued research was encouraged, the existing literature did not show a perioperative spike in clots attributable to HRT.
In summary, the best available evidence indicates that maintaining transdermal estradiol through surgery does not measurably raise the risk of thrombosis in otherwise healthy transgender individuals. On the contrary, abrupt cessation of hormones can have clear negative effects. This evidence base has led expert committees and leading health centers to move away from blanket hormone stoppage policies.
Surgery Type, Anesthesia, and HRT Management
The decision to pause or continue HRT can be influenced by the nature of the surgery, but current guidance generally favors continuation of estradiol regardless of surgery type in patients with no additional risk factors. Key considerations include:
- Major vs. Minor Surgery: Major surgeries (e.g. abdominal or pelvic procedures, orthopedic joint replacements, lengthy reconstructions) inherently carry higher baseline VTE risk due to factors like longer anesthesia time and postoperative immobility. Historically, these were the cases where surgeons most often insisted on stopping estrogen pre-op. For example, early protocols for vaginoplasty (a major gender-affirming surgery) commonly had patients hold estrogen for a few weeks, fearing compounding risk[5]. Now, however, we know that with proper VTE prophylaxis (compression stockings, early mobilization, and if indicated, prophylactic heparin), continuing estradiol does not add significant risk even in major surgeries[13][10]. The Mount Sinai vaginoplasty data showed zero clots in the continued-estrogen group despite vaginoplasty being a lengthy, high-risk operation[11]. Minor surgeries or outpatient procedures (e.g. breast augmentation, minor laparoscopic surgeries, facial cosmetic procedures) have a much lower baseline risk of thrombosis, and thus there is virtually no rationale for stopping HRT in those cases - the clot risk is exceedingly low to begin with, and any theoretical reduction by holding hormones is outweighed by the downsides of discontinuation. In fact, experts have criticized the practice of hormone cessation being "applied to many surgeries outside of vaginoplasty, even those with little VTE risk," calling it an outdated over-correction[22][23]. Today's consensus is that for most surgeries - minor and major alike - transgender patients can remain on transdermal estrogen, provided standard surgical VTE precautions are in place.
- Type of Anesthesia (General vs. Regional/Local): The form of anesthesia itself (general anesthesia vs. regional or local anesthesia) is less directly relevant to estrogen management. The main concern is that general anesthesia often accompanies bigger surgeries that involve longer periods of immobility (which increases clot risk). But estrogen's effect on clotting does not acutely change based on anesthesia type - it's a chronic influence on coagulation, not something that interacts with anesthesia drugs. Thus, there are no specific guidelines suggesting different hormone handling for general vs. local anesthesia. Instead, the focus is on the overall risk profile of the surgery. For a short procedure under local or light sedation, the patient's risk of VTE is so minimal that continuing estrogen is a non-issue. For a multi-hour procedure under general anesthesia, the patient will receive the usual anti-thrombosis measures, and studies indicate estrogen can be safely continued in those circumstances as well[18][12]. Anesthetic societies have published guidance on caring for transgender patients that mention understanding their HRT regimens, but they do not mandate stopping hormones; rather, they emphasize tailoring perioperative care to each patient's needs (e.g. ensuring the correct name/hormone dosing is continued, etc.) and managing standard risk factors (like using appropriate DVT prophylaxis)[24][25].
In practice, many surgeons now categorize transgender patients on estrogen similarly to cisgender women on hormone therapy: if the patient is otherwise low-risk, they do not routinely discontinue HRT for surgery. If a patient has significant risk factors (say, a history of prior deep vein thrombosis, a known thrombophilia, or is extremely immobile and at risk post-op), the surgical team might take a more individualized approach - for example, temporarily lowering the estrogen dose, switching to a transdermal route if not already, or in rare high-risk scenarios, a short pause in concert with aggressive clot prophylaxis. However, for a healthy trans individual with no added risk factors, undergoing surgery with incisions and/or general anesthesia, current expert consensus is that pausing transdermal estradiol is not required[18][6]. The type of surgery (minor vs major) and anesthesia will influence the overall clot prophylaxis strategy, but not the necessity of stopping hormone therapy in an otherwise healthy patient.
Balancing Risks and Benefits
Risk Profile: It bears emphasizing that the absolute risk of perioperative VTE in transgender patients on modern HRT is low. The cohort studies available report VTE rates on the order of 0.1%-0.3% in the perioperative period for those continuing estrogen, which is comparable to general surgical populations[16][10]. Transdermal estradiol in particular has a benign profile; it avoids hepatic first-pass metabolism and does not significantly elevate clotting factors[7]. This means a healthy 30-year-old transfeminine patient on estrogen patches likely has a VTE risk profile approaching that of a pre-menopausal cisgender woman - very low in the absence of other risk modifiers[8]. Standard surgical precautions (such as pneumatic compression devices in the operating room, early ambulation after surgery, and short-course anticoagulant prophylaxis when appropriate) further mitigate the baseline risk for clots in any patient[13]. Thus, continuing HRT usually contributes only a negligible incremental risk, if any.
Consequences of Stopping HRT: On the flip side, the consequences of interrupting hormone therapy can be significant for transgender individuals. Sudden estrogen withdrawal can precipitate acute menopausal-like symptoms (night sweats, hot flashes, irritability) and, importantly, can trigger or worsen gender dysphoria - the distress arising from incongruence between experienced gender and biology. In the perioperative setting, when patients are already stressed and vulnerable, exacerbating dysphoria or causing emotional distress by hormone deprivation is considered detrimental[4]. Some reports have documented patients experiencing depression or even suicidal ideation when forced to stop hormones before surgery[1]. Additionally, cessation may lead to a transient resurgence of undesired masculine features (e.g. oilier skin or even minor muscle mass changes), which can be psychologically upsetting. These factors are not trivial and must be weighed against the theoretical benefit of hormone interruption. As one publication noted, the side effects of stopping estrogen "may be more harmful than the VTE risk itself" in a well-monitored patient[4]. This perspective underlines why guidelines tilt in favor of maintaining treatment: the risk-benefit calculus generally favors continuing estradiol, given the low clot risk and high potential for harm in withholding essential hormone therapy.
Lack of Consensus or Ongoing Debate: While the field is moving toward consensus, it's worth noting any remaining debate. At present, most leading transgender health protocols advise against routine HRT suspension, yet surveys indicate some surgeons and hospitals still have conservative policies. This lingering caution often stems from habit or medicolegal concerns rather than new data. For example, despite WPATH's guidance, one 2025 review observed that many surgeons continue to discontinue estrogen out of custom, even for surgeries with minimal clot risk[23]. However, this practice is increasingly viewed as outdated. As evidence accumulates, a "change in practice" is underway, and more providers are adhering to the updated guidelines allowing hormones to continue[26][27]. In scenarios where there is disagreement (say an individual surgeon still prefers a pause), it often becomes a case-by-case discussion with the patient, weighing that surgeon's anecdotal comfort against prevailing standards and the patient's wellbeing. Importantly, no major medical or surgical association today explicitly requires stopping transdermal estradiol in a low-risk patient - at most, some guidelines say it "may be considered" to hold therapy if a patient has multiple risk factors or in very high-risk operations, but blanket cessation is no longer the standard of care[6].
Conclusion
Current consensus among experts, guidelines, and research is that it is generally not necessary to stop bioidentical transdermal estradiol prior to surgery in a healthy transgender individual with no additional VTE risk factors. WPATH and other authoritative bodies support continuing estrogen through the perioperative period to avoid withdrawal and because evidence shows no increase in postoperative thrombosis rates with transdermal estradiol[10][18]. Transdermal estradiol's safer pharmacologic profile means it poses minimal thrombotic risk - especially relative to older oral estrogens - and parallels data from cisgender women on hormone therapy[7]. Whether the surgery is minor or major, and whether under local or general anesthesia, the prevailing approach is to maintain hormone therapy, alongside standard clot-prevention measures, rather than interrupt a crucial treatment absent clear contraindication.
In summary, for a healthy trans patient on transdermal estrogen, routine preoperative HRT cessation is not indicated[6]. The emphasis is on individualized care: managing known risk factors (if any), ensuring adequate thromboprophylaxis during and after surgery, and keeping the patient physiologically and psychologically stable. By following up-to-date guidelines and evidence, healthcare providers can safely proceed with surgery without forcing a halt to estrogen replacement, thus respecting the patient's gender-affirming needs while maintaining a low risk profile. As always, if unique circumstances apply (e.g. a prior blood clot or an especially prolonged immobilizing surgery), the care team may tailor the plan; but in the typical case of a transgender woman on a stable transdermal HRT regimen, there is broad agreement that therapy can be continued through the surgical period without added danger[18][27]. This approach maximizes patient well-being and surgical outcomes, reflecting the latest in both transgender medicine and perioperative safety research.
Sources:
- Coleman E. et al. (WPATH Standards of Care, Version 8, 2022) - World Professional Association for Transgender Health guidelines[1][2].
- Hembree WC et al. (Endocrine Society Clinical Practice Guideline, 2017) - Endocrine treatment of gender-dysphoric/gender-incongruent persons[3][9].
- Boskey ER et al. JAMA Surgery. 2019;154(2):159-169 - Systematic review of perioperative hormone therapy and surgical risk[6][19].
- Kozato A et al. J Clin Endocrinol Metab. 2021;106(4):e1586-e1590 - Study of VTE outcomes in transgender women undergoing surgery with vs. without estrogen therapy[10][12].
- Li AY et al. Plast Reconstr Surg. 2024;154(6):1309-1315 - Study on continuing estrogen during facial feminization surgery and VTE risk[17][18].
- Mount Sinai Center for Transgender Medicine - Press release summarizing research on perioperative estrogen (2021)[28][27].
- Vinogradova Y et al. BMJ. 2019;364:k4810 - UK observational study on HRT type and VTE risk (via Medscape summary)[7].
- Additional references: Frontiero A et al. Front Endocrinol. 2021 - Meta-analysis on VTE prevalence in transfeminine individuals[8]; Lee AH & Spiegel JH. The Laryngoscope. 2022 - Commentary on perioperative estrogen; Badreddine M et al. Eur Rev Med Pharmacol Sci. 2022 - Discussion of estrogen hold in low-risk surgeries[22][23].
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https://pubmed.ncbi.nlm.nih.gov/40646333/
[2] [11] [13] [14] [15] [26] [27] [28] Study Supports a Change in Practice-Allowing Patients to Remain on Estrogen for Gender-Affirming Surgery
https://reports.mountsinai.org/article/endo2022-_8_transgender_estrogen
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https://pubmed.ncbi.nlm.nih.gov/33417686/
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