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Abstract

The newly released World Professional Association for Transgender Health Standards of Care, 8th Edition specify that adolescents should be offered menstrual suppression as part of their treatment plans to suppress menses and alleviate dysphoria, provide contraception, or improve irregular bleeding on testosterone therapy. This is a review of current evidence-based options for reversible interventions for menstrual suppression in adolescents with gender dysphoria or incongruence. Shared decision-making should be used by the clinician at all times, and the clinician should be intentional in prioritizing the patient’s stated needs and desires when offering interventions. No method should be withheld due to the experience of gender incongruence alone. Contraceptive options offering menstrual suppression include depot-medroxyprogesterone acetate, levonorgestrel intrauterine systems, progestin-only contraceptive pills, and combined hormonal contraceptives. Non-contraceptive options include norethindrone acetate, oral medroxyprogesterone acetate, gonadotropin-releasing hormone analogues/agonists, and danazol. Certain patients may also benefit from non-pharmacologic interventions, such as specialty menstrual underwear.

Plain language summary

Using medicine to stop Menstrual periods in teens with gender incongruence

Summary: Newly released recommendations for the care of teens and young adults with gender dysphoria or incongruence specifically recommend using medications to get rid of menstrual periods if desired or medically necessary. Patients may ask for this to help improve dysphoria, as a feature they want in birth control, or simply because they do not want to have periods. Because temporarily getting rid of periods is something that doctors can do for any patient old enough to have periods, patients with gender dysphoria should also be able to have their periods temporarily stopped using medications if requested. Doctors should ensure that they always help the patient make a decision that is right for them instead of prescribing what they think is right without considering the patient’s input. Options for temporarily getting rid of periods can include birth control, such as oral contraceptive pills, patches, or rings; intrauterine devices; or shots, and it can also be done with things that are not birth control, such a progesterone pills or puberty blockers. Finally, some patients may only need improved period hygiene with period underwear to feel better in their bodies.

Keywords

adolescence contraception gender dysphoria menstrual management

Introduction

Transgender and gender-diverse (TGD) people are individuals whose gender identity and/or gender expression is not in alignment with their sex assigned at birth.¹ Estimates of prevalence of transgender experience range between 0.1% and 0.5%, with some estimates as high as 0.7% of the general population of the United States;² the number of people who experience gender diversity is likely higher. Many TGD adolescents and young adults (AYA) report specific, intense dysphoria surrounding the menstrual cycle,^3,4 with many patients reporting a specific goal of achieving amenorrhea to reduce the sensation of incongruence of the experienced gender and the physical body.

The recently released World Professional Association for Transgender Health (WPATH) Standards of Care, 8th Edition recommend that ‘providers consider prescribing menstrual suppression agents for adolescents experiencing gender incongruence who may not desire testosterone therapy, who desire but have not yet begun testosterone therapy, or in conjunction with testosterone therapy for breakthrough bleeding’.⁵ This recommendation has not been included in previous editions of the Standards of Care, although the medical or social need for menstrual suppression in AYA with anatomy that may result in undesired bleeding has been well established in other populations.^6,7 In this review, we expand on the brief recommendations provided in the 8th edition of the Standards of Care to explore reversible therapies for menstrual management in a gender-informed context.

For a summary of menstrual suppression options that provide contraceptive benefit, please see Table 1. For a summary of menstrual suppression options that do not provide contraceptive benefit, or are not labeled as contraceptives, please see Table 2.

Table 1.

Menstrual management options providing contraception.

Intervention	Dosing schedule	Potential benefit	Potential risk
DMPA (Depo-Provera® or Depo-Subq®)	IM: 150 mg every 11–15 weeks Subcutaneous: 104 mg every 11–15 weeks	• Significant rates of amenorrhea • No estrogen • Subcutaneous preparation can be self-administered in some contexts	• Decreased bone mineral density • Delay in return to fertility • Weight gain
Norethindrone (Micronor® and others)	0.35 mg oral tab once daily	• Once-daily oral option • Inexpensive	• Less effective than other options for menstrual suppression
Drospirenone (Slynd®)	4 mg oral tab once daily	• Once-daily oral option	• Not well studied • Expensive • Anti-androgenic effect
Levonorgestrel intrauterine system (Mirena® and others)	52 mg device placed every 5–7 years	• Long-acting, reversible contraception that does not require user interaction • Effective menstrual suppression	• Insertion can be painful • Requires genital examination • Risks of placement with sedation
Combined hormonal contraceptive pill (numerous brands and formulations)	Typically, 1 pill once a day	• Cheap, effective, widely available, well studied	• Daily intervention • Contains estrogen • Thrombotic risk
Combined hormonal contraceptive patch	Ethinyl estradiol and norelgestromin transdermal system placed on skin once a week for 3 weeks followed by a patch-free week, and then repeated	• Effective • Widely available • Long-acting option with estrogen and without the need to interact with vagina	• Can cause dermatitis in some users • Contains estrogen • Thrombotic risk
Combined hormonal contraceptive vaginal ring	Ethinyl estradiol and etonogestrel vaginal ring placed into the vagina for 21 days, removed for 7 days, and then repeated	• Effective • Widely available • Least frequent interaction of all combined options	• Requires the device to be placed into the vagina, which may be dysphoric • Contains estrogen • Thrombotic risk

DMPA, depot-medroxyprogesterone acetate; IM, intramuscularly.

Table 2.

Menstrual management options not labeled as contraceptives.

Intervention	Dosing schedule	Potential benefit	Potential risk
Norethindrone acetate (Aygestin®)	2.5 to 20 mg PO per day, start with 5 mg	• High rates of amenorrhea • Inexpensive • Widely available	• Peripheral conversion to ethinyl estradiol includes some risk of thrombosis • Daily intervention
Medroxyprogesterone acetate (Provera®)	2.5 to 20 mg PO per day, start with 5 mg	• Inexpensive • Widely available • No conversion to ethinyl estradiol	• Somewhat less effective than other oral options
Danazol (Danocrine®)	50–400 mg PO BID, start with 200 mg PO BID	• Effective suppression • Reversible androgenic effect	• Twice-daily dosing • Can be expensive
Triptorellin acetate (Triptodur®)	22.5mg IM every 6 months	• Effective suppression • Twice-yearly dosing	• Injection • Potential increase in bleeding prior to suppression • Expensive
Depot-leuprolide acetate (Lupron®)	22.5 mg IM every 3 months (most common)	• Effective suppression • Four times a year	• Injection • Potential increase in bleeding prior to suppression • Expensive
Histrelin implant (Supprelin® LA)	50 mg subdermal implant every 12 months	• Effective suppression • Annual intervention	• Expensive • Can be difficult to find a provider to place it • May require several procedures depending on the duration of use
Non-prescription	Numerous, most commonly menstrual underwear	• Readily accessible • Does not necessarily ‘out’ patient as TGD • May be more acceptable to families • No side effects	• No actual impact on the physiology of menstruation

BID, twice daily; PO, orally; IM, intramuscularly; TGD, transgender and gender-diverse.

Shared decision-making framework and equity

There is a real risk of reproductive coercion when marginalized populations seek healthcare services. Examples include persons in American detention facilities who underwent hysterectomies without informed consent as recently as the late 2010s,⁸ the removal of cervical cancer cells from Henrietta Lacks for research and eventual profit,⁹ and the court case Buck v Bell, where the US Supreme Court determined that family members could request surgical sterilization for adults with intellectual disability.¹⁰ These are three high-profile examples of autonomy being removed from the patient with respect to medical decision-making and given to someone else, although the history of medical and legal coercion with respect to reproductive decision-making is long.¹¹ The experience of gender incongruity or dysphoria is another well-documented source of barriers to health equity, including the lack of access to appropriate contraceptive, menstrual, pregnancy-related, and general medical care.^5,12–20 For this reason, a shared decision-making (SDM) model is essential for providing menstrual healthcare to TGD AYA.

SDM frames the patient as the expert in their own needs and the healthcare provider as an expert guide in helping the patient decide which specific interventions best match the patients’ desires.²¹ This is the recommended model for most health domains with respect to gender-related care,^1,2,4,22 and menstrual care should also follow this model.

Within this SDM framework, the provider should first assess what the patient seeks out of menstrual management.^23,24 Does the patient desire complete cessation of menses? Do they specifically desire contraception? Patients may decide that any number of attributes is most important to them, including cost, availability, perceived ‘normalcy’, discretion or privacy, or effectiveness; whichever of these attributes is most important to the patient should be respected by the provider.

SDM requires that the clinician also counsel patients regarding realistic expectations of any specific intervention. No method is guaranteed to provide complete therapeutic amenorrhea, and patients should be counseled that over time rates of amenorrhea with all methods increase but are never 100%.^6,7

Reflexivity statement

The author would like to acknowledge that she is a cisgender, heterosexual individual and as such only has the lived experience of a healthcare provider to patients of various backgrounds, but lacks lived experience necessary for personal insight into the experience of gender incongruence itself. This likely influences the recommendations of this article.²⁵

Methods

OVID Medline and PubMed were searched using the terms ‘adolescent’ and ‘menstrual suppression’, which returned a total of 79 unique results. Of these, 19 were used in this review. The references of these articles were also reviewed, from which a further 20 references were obtained, comprised of 9 policy statements (one of which had a more recent update available) and 11 miscellaneous articles (including several regarding the history of development of various methods). Because this is an evolving field, the literatures of other areas of adolescent gynecology where menstrual suppression is widely recommended were also explored, including search terms ‘catamenial epilepsy’, ‘bleeding disorders’, and ‘intellectual disability’; ‘shared decision making’ was similarly included in this search. This yielded an additional 18 manuscripts. The Food and Drug Administration (FDA) labels of the approximately 16 medications available in the United States at the time of this writing mentioned throughout the other references were also reviewed.

As gender dysphoria in AYA is, as of this writing, a very popular topic among the lay press, recent publications from the New York Times regarding gender dysphoria and reproductive health were also reviewed, as were other publications outside of the medical realm. Four such citations are included, including the US court case Buck v Bell.

The results of this literature review are synthesized in narrative form below.

Testosterone

Current guidelines do not recommend the use of testosterone as a first-line agent to suppress menses alone; it should also not be considered a ‘reversible’ intervention for consent purposes.^5,26,27 In addition, while the newest revision of the WPATH Standards of Care does not specify at what age an individual becomes eligible for specific interventions, including testosterone,⁵ other society guidelines specify a lower age limit of 16 years for this intervention.²⁷ This discrepancy in clinical practice recommendations should be included in SDM conversations if age and reversibility are concerns.

Testosterone therapy alone can offer therapeutic amenorrhea, usually within 3–6 months^3,26,28–30 Many patients will prefer to use testosterone therapy alone to achieve this end, although there are several important caveats to consider, including the possibility that amenorrhea with testosterone therapy alone is not always possible.²⁶ Testosterone, while it does result in amenorrhea, does not provide complete ovulatory suppression and is not a contraceptive;^31–33 in addition, it may cause fetal harm.³⁴ In patients who engage in sexual activity that may result in pregnancy, the use of testosterone alone should not be considered adequate for pregnancy prevention. For patients who are not at risk of pregnancy or who do not desire specific contraception, testosterone without any other specific agent for menstrual suppression in the context of gender incongruence–related healthcare may be appropriate. The initiation of testosterone therapy in TGD AYA should follow all current recommendations regarding assessment of readiness for permanent hormonal interventions and should not be undertaken purely as a menstrual suppressant according to current WPATH Standards of Care.⁵

Progestins

The most diverse class of medications that can be used for menstrual suppression is synthetic progestins^{3,7,24,30,35–40} These medications are available for a wide variety of indications, can be contraceptive if that is a patient’s goal, and have many different methods of delivery. This diversity of use and preparation as well as a generally favorable safety profile makes progestins as a drug class very appealing for menstrual manipulation in adolescents who have a need for it for a broad number of reasons, including disability,⁶ bleeding disorder,⁴¹ catamenial disorders including epilepsy,^42,43 or who simply prefer to avoid menstruation,^7,44 regardless of gender.

In a gender-related context, the absence of estrogen in progestin-only methods of suppression may be seen as a benefit not only in terms of safety profile, as no synthetic progestin carries the same clot risk as ethinyl estradiol (EE), the most widely used synthetic estrogen in contraceptive methods in the United States.⁴⁵ Effective menstrual suppression with progestins may be achieved with pills,^46–48 subcutaneous injection,⁴⁹ intramuscular injection,⁵⁰ and intrauterine devices.⁵¹ Drospirenone 4 mg oral tabs is a relatively new progestin-only contraceptive pill that may offer more reliable contraception than norethindrone, but its use as a menstrual suppressant has not been studied, and its anti-androgenic effect may limit its use in TGD individuals.^30,52 Unfortunately, etonogestrel subdermal implants, while they do provide excellent contraception, do not generally provide reliable menstrual suppression and are less widely used in this context.^{3,30,32,38,53,54}

Norethindrone and norethindrone acetate

Norethindrone (NET) and norethindrone acetate (NETA) are both widely available progestins in the United States, with norethindrone 0.35 mg progestin-only pill labeled for contraceptive use⁵⁵ and NETA 5 mg tablets not labeled for contraceptive use.⁴⁶ While these medications share very similar names, and both enjoy widespread off-label uses, they are not identical compounds. NETA is an acetic acid ester of norethindrone, and as such, it is a different compound with different indications for usage and different pharmacologic characteristics,⁴⁶ with oral NETA 5 mg once daily more likely to result in amenorrhea than oral NET 0.35 once daily, despite its lack of on-label use as a contraceptive.^30,39 For patients who desire menstrual suppression in the form of a daily pill but who either do not require or do not desire contraception, NETA 2.5–20 mg is a reasonable choice for menstrual suppression.^3,30,37,39 In practice, the author recommends that if SDM techniques result in the use of NETA, the initial dose may be 5 mg/day and can increase to up to 20 mg/day by 2.5–5 mg increments every 4–8 weeks as needed to control bleeding or decreased to 2.5 mg/day to control side effects.

There is some peripheral conversion of NETA to EE,⁴⁰ which can limit its use in patients who have a medical contraindication to estrogen, such as a history of stroke or blood clot. This is relatively rare in the pediatric and adolescent population, although to that end if there is a true contraindication to estrogen, the author suggests considering oral medroxyprogesterone acetate (MPA), as discussed below.

Danazol

Danazol is another synthetic progestin that may be used for menstrual management to achieve amenorrhea.³⁵ Its FDA-approved uses are in endometriosis, fibrocystic breast disease, and for the prevention of attacks of hereditary angioedema.⁴⁸

Danazol is a synthetic steroid with both anti-estrogenic and anti-progestogenic properties, as well as some mild androgenic effect.³⁵ The mechanism of action for use of danazol in endometriosis is suppression of both estrogen and progesterone receptors in the endometrium, resulting in thinning of the endometrium and subsequent amenorrhea.^35,48

The androgenic effect of danazol limits its use in cisgender women in need of menstrual suppression: it has side effects of weight gain, breast atrophy, hirsutism, acne, and ‘hoarseness’ or voice change. These changes may or may not be desired by adolescent patients and they should be explored at length with the patient prior to prescription. These are all reversible with cessation of the medication.^35,48 These side effects that limit use in cisgender women may be seen as desirable reversible effects in patients in need of both menstrual suppression and androgenizing therapy without contraceptive need or desire, or who wish to trial a medication with reversible androgenic effects instead of initiation of testosterone therapy. This agent has not been widely studied in transgender adolescents, although the favorable side effect profile (in this context) and effective menstrual suppression make it an appealing option.

Notably, danazol is not labeled for use as a contraceptive and can be teratogenic.⁴⁸ Using an SDM framework, patients with anatomy necessary for pregnancy can all consider this medication in their regimen, although they should be counseled on both the lack of known efficacy as a contraceptive and the possibility of teratogenicity. Patients who do not desire and do not have a need for contraception may find this as a very attractive option; patients using this medication who do have some behavioral risk of pregnancy should be offered separate contraceptive counseling.

As this agent has not been studied as a menstrual suppressant in AYA, dosage is based on labeling for endometriosis. Patients may take 50–400 mg orally twice daily, and titration to effect is recommended.⁴⁸

Depot-medroxyprogesterone acetate and oral MPA

MPA and depot-medroxyprogesterone acetate (DMPA) are two closely related synthetic compounds, with the former being FDA-approved for treatment of secondary amenorrhea and abnormal uterine bleeding due to fibroids and/or uterine cancer as well as for endometrial protection in postmenopausal women taking oral estrogen,⁴⁷ and the latter approved for use as a contraceptive⁵⁰ and for endometriosis pain (subcutaneous preparation only).⁴⁹

MPA is an oral tablet that may be taken daily to suppress menses and abnormal uterine bleeding without specific indication for contraception.⁴⁷ Unlike NETA, it has no peripheral conversion to EE, so in patients who have serious thrombotic risk or contraindication to estrogen, this may be the safer option with similar bleeding profile.⁴⁰ Ovulation is not reliably suppressed at doses less than 10 mg per day.³⁹

If contraception or non-daily intervention for menstrual management is desired, subcutaneous or intramuscular preparations of DMPA may be used. These are both very effective contraceptives and effective menstrual suppressants.^{6,7,23,24,37,39,40,44,53} Both the subcutaneous and intramuscular preparations of DMPA carry a black-box warning from the FDA regarding a deleterious effect on bone health with the use of either of these medications for longer than 2 years, although the risk of fracture with prolonged use of DMPA is less clear.⁵⁶ If patients desire specific contraception, DMPA in either form is an excellent choice although the provider should counsel on the risks of changes to bone health, weight gain, and delay in return to fertility.^49,50

In keeping with the SDM framework, while the adverse effects of DMPA on bone health and weight are apparent, if the patient has a need for contraception, the deleterious effect of DMPA on bone health is probably less impactful than the health and social impacts of pregnancy itself,⁵⁷ and DMPA should not be withheld from adolescents based on this concern alone. An additional consideration in TGD patients is the potential plan for use of testosterone: testosterone is a sex steroid, and as such, it generally improves bone mineral density.³⁴ The impact of testosterone use in TGD AYA previously using DMPA or GnRH agonists, both of which negatively impact bone mineral density, has not been established, but in patients who are concurrently using testosterone and require contraception or in patients who hope to eventually start testosterone therapy, the risk to bone health may be mitigated.

Levonorgestrel intrauterine system

Levonorgestrel-containing intrauterine systems (LNG-IUS) are another potential method of menstrual management that offers a contraceptive benefit. These are small devices that contain variable amounts of the synthetic progestin levonorgestrel which may be placed in the uterus in a short, outpatient procedure and provide between 3 and 7 years of contraception depending on the amount of progestin in the device and variable bleeding control. These devices are well established for the use of menstrual suppression in various adolescent populations and are generally quite well tolerated^{24,30,39,51,54,58–63} For patients who cannot tolerate an in-office procedure, some providers are able to offer LNG-IUS placement with sedation.⁶⁴ At present, only the Mirena® 52 mg LNG-IUS is FDA-approved for use in controlling heavy menses,⁵¹ and as such, it is generally the most widely studied for use as a menstrual suppressant. Of note, LNG-IUS should not be placed within 90 days of an episode of pelvic inflammatory disease.⁶⁰

Using an SDM framework, the LNG-IUS should be offered to patients who desire menstrual suppression with non-daily intervention, regardless of other medication use, sexual activity, or history of pregnancy.^{30,44,54,60,61} This method is very effective at both pregnancy prevention and menstrual suppression, and patients do not need to have both indications to be candidates for this option. Similarly, while this option may be attractive to some providers for all of the above reasons, providers must also acknowledge that the requirement for genital visualization and manipulation for placement is, for some patients, an absolute barrier to use.^4,5,21 Many individuals may also find that post-placement pain and/or bleeding exacerbate dysphoria to an intolerable degree and may seek early discontinuation of the device. That said, the potential for early discontinuation should not be a reason to deny access to LNG-IUS if it is what the patient seeks, in particular as TGD AYA who self-select LNG-IUS for any reason have similar satisfaction rates with this method as non-TGD AYA.¹⁵

GnRH analogues

Gonadotropin-releasing hormone (GnRH) agonists or analogues are approved by the FDA for treatment of central precocious puberty^65,66 and prostate cancer,⁶⁷ although they enjoy several off-label uses, including fertility treatments, endometriosis, uterine fibroids, and other conditions where deprivation of sex hormones is needed.⁶⁸ The mechanism of action for these agents is a negative feedback loop: the GnRH agonist causes a transient increase in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary, which results in a short burst of increased sex steroid production, followed by a prolonged period of suppression of FSH, LH, and sex steroid production.^65–67 In a gender-informed context, they are most frequently used as agents to provide pubertal blockade and halt the progression of gonadal puberty, either to allow time to work with a therapist toward clarifying the patient’s individual body goals or to prevent the progression of known, undesired pubertal changes, as well as allowing time for the cognitive development necessary to participate in informed consent.^5,27

The surge of FSH and LH can result in undesired effects from these medications: shortly after the administration of these medications, there can be a brief increase in sex hormone followed by a drop. This can result in both ovulation and transient undesired withdrawal bleeding, which limits the use of these medications as contraceptives. In addition, the absence of any sex steroid has a deleterious effect on bones, and as a result, these agents are generally not used as initial interventions to control menstrual bleeding despite their high efficacy.^30,32,54

The use of GnRH analogues as first-line menstrual suppressants alone is limited in the current Standards of Care, which specify that patients must consent to these medications the same way for menstrual management as they might for pubertal blockade.⁵ It is important to note that the use of GnRH analogues for menstrual suppression in a person who is also using androgenizing medications is a distinct clinical case from individuals using GnRH analogues alone for blockade of puberty and should involve slightly different counseling in an SDM framework. In particular, if a person initiates pubertal blockade, never completes natal gonadal puberty, and continues on to use non-gonadal sex hormone, this may result in impaired fertility.^5,27 If a person is using a GnRH analogue to suppress menses after completion of gonadal puberty while also using testosterone therapy, this may not be the case.

Combined methods (pills, patches, and rings)

The most widely used method of menstrual management in the United States is, the familiar combined hormonal contraceptive (CHC) pill.^{24,41,44,60,69,70} Combined hormonal contraceptives include oral pills, transdermal patches,⁷¹ and vaginal rings,⁷² all of which contain some combination of estrogen and progestin.⁷³ TGD AYA may prefer to use methods other than CHC for menstrual management or for contraception, as the addition of estrogen to the body may be unwelcome, in terms of both physical symptoms like breast tenderness and the increased dysphoria of using a ‘female’ sex hormone. In the United States, the vast majority of these medications use the synthetic estrogen EE, although there are some emerging options that use either estradiol valerate or esterol.⁴⁵ For the purposes of this article, as the vast majority of CHCs use EE, the risks and benefits of CHCs will be discussed with respect to this specific compound.

EE combined with synthetic progestins offers effective contraception, though not without risk. Over the past several decades, there have been many attempts to reformulate CHCs with lower amounts of EE, due to risk of cardiovascular events and thrombotic events, as well as drug interactions via common metabolism in the CYP 3A4 pathway.^45,70,73

Conventional dosing of oral CHCs involves a pattern of active pills and placebo pills, where a patient takes pills containing EE and a progestin for 21 or 24 days (depending on brand), followed by 7 or 3 days of pills containing no active ingredients, for a predictable 28-day cycle.⁷³ In people desiring menstrual suppression for any reason, this schedule may be altered to contain fewer scheduled episodes of bleeding or no episodes at all.^{6,7,24,30,32,37} The potential benefit of menstrual suppression with contraceptive benefit in pill, patch, or ring form (as opposed to injection or intrauterine device) may be very appealing to some patients, although it must be balanced with the potential thrombotic and cardiovascular risks of EE.⁷³ Any brand or form of CHC may be used for menstrual suppression, as inactive pills and patch- or ring-free weeks can be safely skipped and active medication can be used continuously. There is a risk of breakthrough bleeding with this approach, which has been most widely studied with oral CHCs, and rates of amenorrhea improve over time.⁷

Current recommendations for AYA seeking contraception alone and prioritizing efficacy recommend long-acting reversible contraceptives over all forms of CHC due to ease of use, improved efficacy, and better safety profile^{58,60,61,74–76} An additional concern for those with gender incongruence may be that the use of estrogen may result in breast tenderness, as well as reducing the effectiveness of androgenizing regimens.^5,17,26 For this reason, use of an SDM framework again highlights that the most common method of contraception and menstrual suppression is not the only method available, and the patient’s needs should guide what interventions are offered. If a patient desires CHCs for menstrual suppression, they should be provided high-quality risks and benefits counseling – the same as with all other medical interventions – and if there are no medical contraindications and CHCs can be reasonably expected to achieve the patient’s goals, these methods should be considered. For medication safety reasons, if patients are neutral to ambivalent about methods of menstrual management, other options may be more appropriate. Clinicians should also be mindful that use of the vaginal ring may increase dysphoria in some patients.^4,30

Non-pharmacologic interventions

Some patients do not request, require, or have access to specific medical management of menstruation, and instead are interested in non-pharmacologic interventions to alleviate menstrual dysphoria. Non-pharmacologic options can include menstrual underwear or optimization of menstrual hygiene alone.

Menstrual underwear is a type of reusable specialty undergarment meant to absorb the flow of any liquids from the genitals.⁷⁷ These undergarments typically have the appearance of conventional underwear, including coming in a variety of different cuts and styles, with many manufacturers selling ‘gender-neutral’ models marketed specifically to TGD populations. The liner of menstrual underwear is usually black, which minimizes the appearance of the blood. If the patient’s primary goal in menstrual management is reduction of the appearance of blood and they are not, as such, bothered by pain, heavy flow, cyclic symptoms such as breast tenderness, or other issues that may involve medication management, menstrual underwear may be an ideal option. Menstrual underwear may also be preferred by adolescents who live in a family structure or environment where specific medical interventions for menstrual management are not desired or feasible.

Future directions

The area of menstrual management in TGD AYA is a developing and rapidly changing area, where different disciplines may offer very different perspectives on how to meet the asserted needs of the patient while minimizing potential harm. For example, some clinicians may choose to prioritize bone health concerns over risks of estrogen exposure, and therefore recommend the use of CHCs over GnRH analogues as an initial step to menstrual management, where another provider may have concerns about the physical effects of estrogen, such as breast growth, in an adolescent who already experiences a good deal of distress surrounding the development of secondary sex characteristics. All of these clinicians have valid perspectives, which is why the patient’s priorities and risk tolerance should be centered using an SDM model.

Areas of potential future study include evaluations of the tolerability of various methods of menstrual suppression in adolescents of various asserted genders, effect of testosterone on the efficacy of various contraceptives (including emergency contraceptives), or if use of a menstrual suppressant impacts the timeline for testosterone-related amenorrhea alone. For clinicians who practice in this area, frequent changes in the literature require the clinician to be alert to new possibilities for management, as well as openness to the possibility of changes in clinical recommendations.

At present, there are very few options for menstrual management that are not some sort of hormonal medication, although moving forward there are many promising options. One class of medications, selective progesterone receptor modulators (SPRMs), may represent an interesting direction in the field. These agents can offer treatment for breast cancer, endometrial disorders, estrogen-free contraception, and treatment of uterine fibroids.⁷⁸ In the United States, two such agents are available: ulipristal acetate⁷⁹ and mifepristone.⁸⁰ Mifepristone is approved only for induction of abortion up to 70 days’ gestation, and as such, it is subject to numerous restrictions in prescribing.⁸⁰ For this reason, it is unlikely to be used in menstrual management alone.

While there are selective estrogen receptor modulators (SERMs) that enjoy wide use as chemotherapeutic agents and have some utility in controlling abnormal uterine bleeding in a very specific set of circumstances (such as short-term use of tamoxifen for control of etonogestrel implant–related bleeding),⁸¹ their side effect and risk profiles make them inappropriate choices for use in menstrual management alone in AYA.⁸²

Ulipristal acetate is an SPRM approved for use as an emergency contraceptive due to its ability to suppress ovulation,⁷⁹ and it has also demonstrated effectiveness in treatment of uterine fibroids with associated amenorrhea. While this agent is effective as a contraceptive, reliably induces amenorrhea, and reduces pain, safety concerns related to hepatic injury further limit its use as an oral agent.^78,83

A final developing modality is a copper-containing intrauterine system (Cu-IUS) which also contains a small dose of ulipristal acetate. The developers of this device hope to offer highly effective intrauterine contraception that is not burdened by the increase in bleeding and pain that is often seen with Cu-IUS^73,84 and instead might offer hormone-free menstrual suppression.⁸⁵ This device is still in development and is therefore several years away from availability, but it may represent an interesting option for TGD AYA who do not desire the presence of any hormone, but desire menstrual suppression.

Conclusions and recommendations

There are many different approaches to menstrual management that meet the newly stated WPATH Standards of Care recommendation for menstrual suppression outside of testosterone use, including GnRH agonists, progestins, contraceptives, and non-prescription interventions, with several promising developments on the horizon. There is no single intervention that meets the needs of all individuals in all circumstances, regardless of the gendered experience. The recommended approach is SDM between the patient and the clinician, with the patients’ needs and priorities informing the order in which the clinician presents various available interventions. We recommend any intervention be given at least 3 months’ trial to determine the effectiveness, as most of the interventions here require 3–6 months to truly demonstrate impact on menstrual bleeding. We also recommend that clinicians are clear with their patients that testosterone is not a contraceptive, and contraceptive needs should be routinely reassessed. We also recommend that GnRN analogues may be used for menstrual suppression if other options have been trialed without success or if puberty blockade is otherwise desired, and we recommend consideration of danazol in patients who do not need contraception, can tolerate twice-daily dosing, and may be interested in androgenic side effects. The presence of gender incongruence should not reduce the amount of options offered to any particular patient but instead should be honored by the prescribing clinician while the patient’s stated priorities are centered.

Footnotes

Acknowledgements

None.

Declarations

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Reversible interventions for menstrual management in adolescents and young adults with gender incongruence

Abstract

Plain language summary

Keywords

Introduction

Shared decision-making framework and equity

Reflexivity statement

Methods

Testosterone

Progestins

Norethindrone and norethindrone acetate

Danazol

Depot-medroxyprogesterone acetate and oral MPA

Levonorgestrel intrauterine system

GnRH analogues

Combined methods (pills, patches, and rings)

Non-pharmacologic interventions

Future directions

Conclusions and recommendations

Footnotes

Acknowledgements

Declarations

References