Advertisement

Hormonal Contraceptives, Intrauterine Devices, Gonadotropin-releasing Hormone Analogues and Testosterone: Menstrual Suppression in Special Adolescent Populations

  • Shashwati Pradhan
    Affiliations
    Division of Pediatric and Adolescent Gynecology, Washington Hospital Center, Children's National Medical Center, Georgetown University, Washington, DC
    Search for articles by this author
  • Veronica Gomez-Lobo
    Correspondence
    Address correspondence to: Veronica Gomez-Lobo, MD, Department of Obstetrics and Gynecology, Washington Hospital Center, 110 Irving Street NW, Rm 5B41, Washington, DC 20010; Phone (202) 877-3029; fax: 301-451-2857
    Affiliations
    Division of Pediatric and Adolescent Gynecology, Washington Hospital Center, Children's National Medical Center, Georgetown University, Washington, DC
    Search for articles by this author
Published:April 10, 2019DOI:https://doi.org/10.1016/j.jpag.2019.04.007

      Abstract

      Menstrual suppression (the use of hormonal contraceptive methods to eliminate or significantly decrease the frequency of menstrual cycles) is frequently used in the adolescent population for the management of menstrual symptoms such as heavy or painful periods, premenstrual syndrome, menstrual migraines, or even for patient preference. However, in cases of menstrual suppression in special populations additional risks and benefits need to be considered. The purpose of this article is to review the options and medical considerations for menstrual suppression in patients undergoing chemotherapy who might be at risk of abnormal uterine bleeding, those with intellectual or physical disability, and transgender and gender nonbinary individuals.

      Key Words

      Introduction

      Since the establishment that monthly menses could be manipulated to achieve amenorrhea or at least less frequent menstrual cycles, menstrual suppression with hormonal contraceptives has become an accepted practice.
      • Hillard P.A.
      Menstrual suppression: current perspectives.
      Menstrual suppression is often used to treat issues such as heavy or painful menses, as well as to improve symptoms in patients with chronic pain or those with migraines, mood issues, nausea, or bloating associated with menses. In specific patient populations such as those with an oncologic diagnosis, developmental and physical disabilities, and transgender and gender nonbinary patients, achieving amenorrhea or less frequent menstrual bleeding requires some additional considerations as well as discussion of some other options not used in routine settings. In this review, in addition to the use of hormonal contraceptive options for menstrual suppression, we also discuss the use of gonadotropin-releasing hormone (GnRH) agonists in oncology patients and the effect of testosterone therapy on menstrual bleeding in transgender individuals.

      Hormonal Methods of Menstrual Suppression

      Combined Hormonal Contraceptives

      Combined oral contraceptives (COCs) come in different combinations of levels of ethinyl estradiol (ranging from 10 μg-50 μg) with different doses and generations of progesterone. Traditional dosing intervals can be 21-24 days of active medication with a 4-7 day placebo break. However, several extended cycle regimens have been introduced which range from 42-84 days with a subsequent placebo or low-dose estrogen-only week. Patients can also be instructed to take active medication until breakthrough bleeding occurs when a pill break and a hormone-free interval is started (usually 4 days). With initiation, irregular or breakthrough bleeding is a known side effect; however, irregular bleeding decreases with prolonged use.
      • Hee L.
      • Kettner L.O.
      • Vejtorp M.
      Continuous use of oral contraceptives: an overview of effects and side-effects.
      • Wiegratz I.
      • Kuhl H.
      Long-cycle treatment with oral contraceptives.
      In a randomized study that compared continuous with cyclic COC use, amenorrhea was seen in 79% of continuous COC users at pill pack number 13.
      • Teichmann A.
      • Apter D.
      • Emerich J.
      • et al.
      Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial.
      Lower-dose estrogen COCs are associated with increased breakthrough bleeding and therefore COCs with ethinyl estradiol dose greater than 20 μg are usually used if menstrual suppression is the primary goal.
      • Archer D.F.
      • Nakajima S.T.
      • Sawyer A.T.
      • et al.
      Norethindrone acetate 1.0 milligram and ethinyl estradiol 10 micrograms as an ultra low-dose oral contraceptive.
      • Gallo M.F.
      • Nanda K.
      • Grimes D.A.
      • et al.
      20 μg versus >20 μg estrogen combined oral contraceptives for contraception.
      In addition, the use of 30-35 μg ethinyl estradiol COCs has been advocated because studies have shown that when adolescent patients have prolonged use of COCs containing less than 30 μg of estrogen, bone mineral density (BMD) might be adversely affected.
      • Scholes D.
      • Ichikawa L.
      • LaCroix A.Z.
      • et al.
      Oral contraceptive use and bone density in adolescent and young adult women.
      • Baison T.P.
      • Goldberg T.B.L.
      • Kurokawa C.S.
      • et al.
      Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period.
      The vaginal ring can also be used in an extended manner as well with the insertion of a new vaginal ring every 3 weeks. Studies of extended-cycle vaginal ring users shows excellent efficacy and amenorrhea rates.
      • Miller L.
      • Verhoeven C.H.
      • Hout J.I.
      Extended regimens of the contraceptive vaginal ring: a randomized trial.
      • Guazelli C.A.
      • Barreiros F.A.
      • Barbosa R.
      • et al.
      Extended regimens of the vaginal contraceptive ring: cycle control.
      • Barreiros F.A.
      • Guazzelli C.A.
      • de Araujo F.F.
      • et al.
      Bleeding patterns of women using extended regimens of the contraceptive vaginal ring.
      Similar satisfaction has been noted with extended use of the transdermal contraceptive with placement of a new patch weekly.
      • Stewart F.H.
      • Kaunitz A.M.
      • Laguardia K.D.
      Extended use of transdermal norelgestromin/ethinyl estradiol: a randomized trial.
      Similar to COCs, if breakthrough bleeding occurs when using the transdermal patch or vaginal ring in a continuous fashion, patients can take a break from the patch or vaginal ring for a hormone-free interval before restarting the method.

      Progestin-Only Methods

      Progestin-only methods of hormonal contraception, including depo-medroxyprogesterone acetate (DMPA) injection, levonorgestrel intrauterine device (IUD), progestin-only pills, and the etonogestrel implant, can be used for menstrual suppression with varying levels of efficacy. Because of excellent amenorrhea rates and overall ease of use, DMPA and levonorgestrel IUD are frequently used forms of progestin-only methods for menstrual suppression. DMPA users report improving amenorrhea rates with continued usage with 46% reporting amenorrhea at 1 year of use.
      • Hubacher D.
      • Lopez L.
      • Steiner M.J.
      • et al.
      Menstrual pattern changes from levonorgestrel subdermal implants and DMPA: systematic review and evidence-based comparisons.
      • Arias R.D.
      • Jain J.K.
      • Brucker C.
      • et al.
      Changes in bleeding patterns with depot medroxyprogesterone acetate subcutaneous injection 104 mg.
      Levonorgestrel IUD users also achieve excellent rates of amenorrhea (50% amenorrhea at 1 year; 60% with continued use of the IUD at 5 years).
      • Hillard P.A.
      Menstrual suppression: current perspectives.
      • Adeyemi-Fowode O.A.
      • Santos X.M.
      • Dietrich J.E.
      • et al.
      Levonorgestrel-releasing intrauterine device use in female adolescents with heavy menstrual bleeding and bleeding disorders: single institution review.
      • Rönnerdag M.
      • Odlind V.
      Health effects of long-term use of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use.
      • Hidalgo M.
      • Bahamondes L.
      • Perrotti M.
      • et al.
      Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years.
      In addition, although amenorrhea might not be achieved, another 25% of patients reported oligomenorrhea while using the levonorgestrel IUD with rates of unscheduled spotting in only 11% of users at 2 years.
      • Hidalgo M.
      • Bahamondes L.
      • Perrotti M.
      • et al.
      Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years.
      It should be noted that amenorrhea rates for the levonorgestrel IUD are highest when the 52-mg IUD approved for 5 years is used as opposed to other forms of the levonorgestrel IUD, which have overall lower daily dosage of hormone and also lower amenorrhea rates.
      • Grandi G.
      • Farulla A.
      • Sileo F.G.
      • et al.
      Levonorgestrel-releasing intra-uterine systems as female contraceptives.
      • Nelson A.L.
      Levonorgestrel-releasing intrauterine system (LNG-IUS 12) for prevention of pregnancy for up to five years.
      • Nelson A.L.
      LNG-IUS 12: a 19.5 levonorgestrel-releasing intrauterine system for prevention of pregnancy for up to five years.
      The 52-mg IUD that is approved for 3 years has amenorrhea rates of 19% at 12 months and 38% at 3 years.
      The 13.5 mg IUD approved for 3 years has an amenorrhea rate of 6% at 1 year and 12% at 3 years.
      • Gemzell-Danielsson K.
      • Schellschmidt I.
      • Apter D.
      A randomized, phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena.
      The 19.5 mg IUD approved for 5 years has amenorrhea rate of 12% at 1 year.
      Although excellent for contraception, the copper IUD is not used for the goal of menstrual suppression.
      Progestin-only pills can also be used for menstrual suppression in individuals who do not desire or have a contraindication for estrogen. Improved rates of amenorrhea can be achieved with uptitration of medications such norethindrone acetate or medroxyprogesterone acetate (daily up to 3 times per day dosing) with reports citing up to 76% amenorrhea rates at 2-year follow-up.
      • Hillard P.A.
      Menstrual suppression: current perspectives.
      • Altshuler A.L.
      • Hillard P.J.
      Menstrual suppression for adolescents.
      • Molsa P.K.
      Inducement of therapeutic amenorrhea in mentally retarded women: two-year follow-up study.
      However, escalating doses of progestin-only pills might not be well tolerated with side effects such as weight gain and mood changes.
      • Altshuler A.L.
      • Hillard P.J.
      Menstrual suppression for adolescents.
      Progestin-only medication such as norethindrone 0.35 mg (“minipill”) can be used as well for menstrual suppression; however, in addition to issues with need for strict compliance and breakthrough bleeding, amenorrhea rates are poor with only 10% of patients achieving menstrual suppression with this method.
      • Hillard P.A.
      Menstrual suppression: current perspectives.
      • Altshuler A.L.
      • Hillard P.J.
      Menstrual suppression for adolescents.
      • Broome M.
      • Fotherby K.
      Clinical experience with the progestogen-only pill.
      The etonogestrel implant, although an excellent contraceptive option, functions poorly if the desired outcome is menstrual suppression, with reported amenorrhea rates of 13% at 12 months of use and higher rates of irregular bleeding.
      • Hubacher D.
      • Lopez L.
      • Steiner M.J.
      • et al.
      Menstrual pattern changes from levonorgestrel subdermal implants and DMPA: systematic review and evidence-based comparisons.
      Table 1 summarizes methods, doses, amenorrhea rates and considerations for menstrual suppression methods discussed.
      Table 1Medications for Menstrual Suppression
      MethodDoseAmenorrhea RatesConsiderations
      COCsDifferent dosage levels of ethinyl estradiol and different generations of progestins; monophasic COCs used in continuous fashion (1 tablet daily) without use of placebo weekAlmost 80% at 1 year of use
      • Teichmann A.
      • Apter D.
      • Emerich J.
      • et al.
      Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial.
      VTE consideration in immobile patients

      Interactions with antiepileptic medications

      BTB
      PO progestin-only medicationsNorethindrone 0.35 mg; daily PO medication

      Norethindrone acetate, medroxyprogesterone acetate; PO medications with uptitration of doses (once to 3 times daily) as required
      Low efficacy
      • Hillard P.A.
      Menstrual suppression: current perspectives.
      • Altshuler A.L.
      • Hillard P.J.
      Menstrual suppression for adolescents.
      • Broome M.
      • Fotherby K.
      Clinical experience with the progestogen-only pill.


      Improved efficacy compared with norethindrone; 76% at 2 years
      • Hillard P.A.
      Menstrual suppression: current perspectives.
      • Altshuler A.L.
      • Hillard P.J.
      Menstrual suppression for adolescents.
      • Molsa P.K.
      Inducement of therapeutic amenorrhea in mentally retarded women: two-year follow-up study.
      Ideal if estrogen is contraindicated and PO medication is desired by patient

      BTB and especially with norethindrone need for strict compliance
      Depo-medroxyprogesterone acetate injection150 mg intramuscular (most commonly used); can also be given 104 mg subcutaneously

      Injections every 12 weeks; might shorten interval if BTB occurs
      46% at 1 year of use
      • Hubacher D.
      • Lopez L.
      • Steiner M.J.
      • et al.
      Menstrual pattern changes from levonorgestrel subdermal implants and DMPA: systematic review and evidence-based comparisons.
      • Arias R.D.
      • Jain J.K.
      • Brucker C.
      • et al.
      Changes in bleeding patterns with depot medroxyprogesterone acetate subcutaneous injection 104 mg.
      Irregular BTB, weight gain, and issues regarding bone mineral density with prolonged use
      IUD20 μg per day released by 52-mg levonorgestrel IUD approved for 5 years

      Additional IUD doses

      52 mg 3-year IUD; 19.5 mg 5-year; 13.5 mg 3-year
      52 mg 5-year

      50% at 1 year; 60% at 5 years of continuous use
      • Hillard P.A.
      Menstrual suppression: current perspectives.
      • Adeyemi-Fowode O.A.
      • Santos X.M.
      • Dietrich J.E.
      • et al.
      Levonorgestrel-releasing intrauterine device use in female adolescents with heavy menstrual bleeding and bleeding disorders: single institution review.
      • Rönnerdag M.
      • Odlind V.
      Health effects of long-term use of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use.
      • Hidalgo M.
      • Bahamondes L.
      • Perrotti M.
      • et al.
      Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years.
      (see text for amenorrhea rates for other IUD types)
      Requires procedure for placement; patients with disabilities (physical or developmental) might require sedation/general anesthesia for placement
      GnRH agonistDifferent formulations; most common is leuprolide acetate 11.25 mg given every 12 weeks usually for a maximum duration of 6 monthsNearing 100% efficacy in menstrual suppression
      • Chiusolo P.
      • Salutari P.
      • Sica S.
      • et al.
      Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the prevention of menstrual bleeding in premenopausal women undergoing stem cell transplantation.
      • Meirow D.
      • Rabinovici J.
      • Katz D.
      • et al.
      Prevention of severe menorrhagia in oncology patients with treatment-induced thrombocytopenia by luteinizing hormone-releasing hormone agonist and depo-medroxyprogesterone acetate [erratum in 2007; 110:936].
      • Laufer M.R.
      • Townsend N.L.
      • Parsons K.E.
      • et al.
      Inducing amenorrhea during bone marrow transplantation. A pilot study of leuprolide acetate.
      • Lhomme C.
      • Brault P.
      • Bourhis J.H.
      • et al.
      Prevention of menstruation with leuprorelin (GnRH agonist) in women undergoing myelosuppressive chemotherapy or radiochemotherapy for hematological malignancies: a pilot study.
      (might have increased bleeding with initiation because of transient increase in gonadotropins and steroid hormones)
      Ideal for patients requiring suppression for a short period of time (such as during chemotherapy); prolonged use not advised because of issues with bone density and menopausal symptoms; length of treatment can be extended with use of add-back therapy
      • Surrey E.S.
      • Hornstein M.D.
      Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up.
      • DiVasta A.D.
      • Feldman H.A.
      • Sadler Gallagher J.
      • et al.
      Hormonal add-back therapy for females treated with gonadotropin-releasing hormone agonist for endometriosis: a randomized controlled trial.
      • Chwalisz K.
      • Surrey E.
      • Stanczyk F.Z.
      The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis.
      BTB, breakthrough bleeding; COC, combined oral contraceptive; GnRH, gonadotropin-releasing hormone; IUD, intrauterine device; PO, oral; VTE, venous thromboembolism.

      Special Populations

      Patients with Developmental and Physical Disabilities

      Patients with developmental and physical disabilities have a wide spectrum of abilities with some having only physical disabilities such as patients with spinal cord injury, whereas others might have a developmental disability that has intellectual as well as physical manifestations. When patients with disabilities and their families/caregivers present for discussion of menstrual suppression, it is important to undertake a detailed discussion addressing who desires menstrual suppression and why menstrual management is desired. Patients and caregivers might desire menstrual suppression for a multitude of reasons. For example, patients with physical disabilities might report that menstrual hygiene is difficult because of limited mobility and would prefer suppression of menses. In addition, with the start of menses, caregivers of patients with developmental disabilities might report mood swings, self-mutilation, or other behavioral changes surrounding menses, which might be the patients’ way to express pain or distress.
      American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
      • Kirkham Y.A.
      • Ornstein M.P.
      • Aggarwal A.
      • et al.
      Menstrual suppression in special circumstances.
      • Grover S.
      Menstrual and contraceptive management in women with intellectual disability.
      In these circumstances, initiation of menstrual suppression might be helpful for control of menstrual-related symptoms.
      Importantly, some caregivers might present before the onset of menarche to discuss menstrual suppression. Although counseling can be conducted, to ensure the absence of an obstructive congenital anomaly, demonstrate a functional hypothalamic-pituitary-gonadal axis and endogenous estrogen production, no method should be initiated before the onset of menses.
      American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
      • Kirkham Y.A.
      • Ornstein M.P.
      • Aggarwal A.
      • et al.
      Menstrual suppression in special circumstances.
      It is also important to discuss whether caregivers or patients are also concerned about contraception. Although often thought of as an asexual population, patients with developmental and physical disabilities lead sexual lives. This discussion presents an excellent educational opportunity for a frank conversation about puberty, sexuality, and issues of consent in an individualized and developmentally appropriate manner, which can help to ensure that contraceptive goals are also achieved. In addition, this patient population is vulnerable to sexual abuse.
      • Hornor G.
      • Fischer B.A.
      Child sexual abuse revictimization: child demographics, familial psychosocial factors, and sexual abuse case characteristics.
      Therefore, a discussion about suspicion for abuse is imperative as well as counseling that menstrual suppression and contraception cannot prevent sexual abuse.
      American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
      When patients with developmental or physical disabilities present for evaluation and describe a history of heavy or irregular menses, a thorough history should be undertaken because there are several reasons for menstrual irregularity in these individuals. For example, patients with Trisomy 21 have been shown to have a higher incidence of thyroid disease, which can lead to menstrual irregularities.
      American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
      • Lavigne J.
      • Sharr C.
      • Elsharkawi I.
      • et al.
      Thyroid dysfunction in patients with Down syndrome: results from a multi-institutional registry study.
      In addition, patients with disabilities might be receiving medications that might lead to abnormal menstruation. For example, antipsychotic medications and antidepressants can lead to hyperprolactinemia (Table 2) and some antiseizure medications such as valproic acid might lead to signs of hyperandrogenic anovulation.
      • Molitch M.E.
      Medication-induced hyperprolactinemia.
      Because hyperprolactinemia might be associated with amenorrhea, it can be tolerated if menstrual suppression is a goal and no structural causes (such as a prolactinoma) are identified. However, providers should consider that hyperprolactinemia is associated with adverse effects on BMD (due to the hypoestrogenic state) and galactorrhea and therefore ensure appropriate monitoring of symptoms and BMD.
      Table 2Medications with Highest Risk of Causing Hyperprolactinemia
      • Molitch M.E.
      Medication-induced hyperprolactinemia.
      Class of DrugName of Drug
      Antipsychotics (typical)Phenothiazines (chlorpromazine, thioridazine, mesoridazine, trifluoperazine, fluphenazine, perphenazine)

      Thioxanthenes (thiothixene)

      Butyrophenones (haloperidol)
      Antipsychotics (atypical)Risperidone

      Molindone
      AntidepressantsTricyclics (clomipramine)

      MAO inhibitors (pargyline, clorgiline)
      MAO, monoamine oxidase.
      Most hormonal options for menstrual suppression can be used in this patient population, but several considerations need to be taken on the basis of the medical history of the patient. If there are no medical contraindications for use of COCs, physical or intellectual disability is not a direct contraindication in these patients. These medications can be used in cyclic fashion or in continuous fashion as discussed previously. If the patient is currently receiving antiepileptic medications such as lamotrigine or valproate, it is important to counsel that serum levels of these medication might decrease with concurrent use of estrogen, thus increasing the risk of seizure activity.
      • Reimers A.
      • Brodtkorb E.
      • Sabers A.
      Interactions between hormonal contraception and antiepileptic drugs: clinical and mechanistic considerations.
      Similarly, antiepileptic medications that are cytochrome P450 enzyme-inducing accelerate conversion of estrogen and progesterone to inactive metabolites and decrease serum concentrations leading to issues with decreased contraceptive efficacy and breakthrough bleeding.
      • Reimers A.
      • Brodtkorb E.
      • Sabers A.
      Interactions between hormonal contraception and antiepileptic drugs: clinical and mechanistic considerations.
      Table 3 shows common antiepileptic medications used and their interaction with COCs.
      • Reimers A.
      • Brodtkorb E.
      • Sabers A.
      Interactions between hormonal contraception and antiepileptic drugs: clinical and mechanistic considerations.
      • Carl J.S.
      • Weaver S.P.
      • Tweed E.
      • et al.
      Effect of antiepileptic drugs on oral contraceptives.
      If a patient is wheelchair-bound or otherwise has limited mobility, there is controversy about the risk of venous thromboembolism (VTE) with use of COCs. There is additional concern with use of transdermal patches in patients with limited mobility because studies have shown a twofold increased risk of VTE with use of patches compared with COCs.
      • Galzote R.M.
      • Rafie S.
      • Teal R.
      • et al.
      Transdermal delivery of combined hormonal contraception: a review of the current literature.
      However, the patch might be ideal in patients with issues swallowing or with malabsorptive gastrointestinal disorders.
      • Kirkham Y.A.
      • Ornstein M.P.
      • Aggarwal A.
      • et al.
      Menstrual suppression in special circumstances.
      The vaginal ring might be difficult to place in some individuals with physical disabilities, and on occasion caregivers/partners can assist with placement.
      American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
      In patients with developmental and physical disabilities, however, careful consideration of patient autonomy and privacy as well as caregiver comfort should be undertaken before considering caregiver placement of the vaginal ring.
      Table 3Drug-Drug Interactions between Combined Oral Contraceptives and Antiepileptic Medications
      AEDAED Efficacy Reduced by COC
      • Reimers A.
      • Brodtkorb E.
      • Sabers A.
      Interactions between hormonal contraception and antiepileptic drugs: clinical and mechanistic considerations.
      COC Affected by AED
      • Carl J.S.
      • Weaver S.P.
      • Tweed E.
      • et al.
      Effect of antiepileptic drugs on oral contraceptives.
      phenobarbitalUnknownYes
      phenytoinUnknownYes
      carbamazepineUnknownYes
      topiramateUnknownYes
      valproateYesNo
      gabapentinUnknownNo
      lamotrigineYesNo
      levetiracetamNoNo
      AED, antiepileptic drug; COC, combined oral contraceptive.
      Intramuscular depo-medroxyprogesterone injections given every 12 weeks remains an option for patients, with excellent amenorrhea rates. The dosing interval can be shortened if patients have issues with breakthrough bleeding toward the end of the 12-week dosing schedule. Concern in this specific patient population are twofold: first is the issue of long-term bone health because studies have shown decreased BMD in adolescent patients using DMPA compared with adolescent patients using COCs or no contraception.
      • Cromer B.A.
      • Bonny A.E.
      • Strager M.
      • et al.
      Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study.
      • Scholes D.
      • LaCroix A.Z.
      • Ichikaw L.E.
      • et al.
      Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception.
      American College of Obstetrics and Gynecology Committee on Adolescent Health Care: ACOG Committee Opinion No. 602. Depot medroxyprogesterone acetate and bone effects.
      However, BMD values were shown to be stable after 12 months of use and did rebound after discontinuation.
      • Cromer B.A.
      • Bonny A.E.
      • Strager M.
      • et al.
      Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study.
      • Scholes D.
      • LaCroix A.Z.
      • Ichikaw L.E.
      • et al.
      Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception.
      American College of Obstetrics and Gynecology Committee on Adolescent Health Care: ACOG Committee Opinion No. 602. Depot medroxyprogesterone acetate and bone effects.
      Therefore, with discussion of risk and benefit, continuation of DMPA is a viable option in patients with disability if DMPA is functioning well for menstrual suppression. Dual energy x-ray absorptiometry (DEXA) evaluation can be conducted once in patients who have prolonged DMPA use to assess the effect of the medication on BMD.
      • Kirkham Y.A.
      • Ornstein M.P.
      • Aggarwal A.
      • et al.
      Menstrual suppression in special circumstances.
      This should especially be considered in patients who might be immobile or wheelchair-bound because their risk of decreased BMD might be further heightened by prolonged DMPA use.
      • Kirkham Y.A.
      • Ornstein M.P.
      • Aggarwal A.
      • et al.
      Menstrual suppression in special circumstances.
      The second concern with DMPA use focuses on weight gain. Studies show that patients with weight gain in the first 6 months are at continued risk of significant weight gain with further DMPA use.
      • Bonny A.E.
      • Secic M.
      • Cromer B.
      Early weight gain related to later weight gain in adolescents on depot medroxyprogesterone acetate.
      Weight gain can be particularly challenging for those who self-transfer or need the assistance of caregivers for transfers.
      American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
      • Kirkham Y.A.
      • Ornstein M.P.
      • Aggarwal A.
      • et al.
      Menstrual suppression in special circumstances.
      The levonorgestrel IUD presents an excellent form of menstrual suppression in this patient population with good amenorrhea rates as well as lack of daily or every 12 week medication delivery. In addition, drug interactions are low, which is a relative benefit because this patient cohort is often taking multiple other medications. Studies have shown that progesterone-containing IUDs do not affect the concentrations of antiepileptic medications and therefore do not affect their efficacy making them an ideal option for patients with seizure disorders.
      • Davis A.R.
      • Saadatmand H.J.
      • Pack A.
      Women with epilepsy initiating a progestin IUD: a prospective pilot study of safety and acceptability.
      • Vieira C.S.
      • Pack A.
      • Roberts K.
      • et al.
      A pilot study of levonorgestrel concentrations and bleeding patterns in women with epilepsy using a levonorgestrel IUD and treated with antiepileptic drugs.
      In individuals with physical disability, placement might need to be done with anesthesia because of issues such as contractures, which might hinder in-office placement. Patients with developmental disability have a wide range of presentations and some might tolerate an in-office placement with reassurance and guidance and others might require placement with sedation. Although preprocedure ultrasound examination is not necessary in adolescents, in patients who require anesthesia for placement, preplacement ultrasound examination might be helpful to ensure appropriate uterine cavity length before the procedure to avoid unnecessary anesthesia exposure.
      Although it is often requested by parents or caregivers for alleviation of symptoms and because of fear of pregnancy, surgical management is not indicated as initial treatment for menstrual suppression in this patient population. Endometrial ablation is associated with high rates of failure to achieve amenorrhea in adolescents and cannot be used as a form of contraception or sterilization.
      American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
      Intrauterine scarring, contractures, and cervical stenosis occurring after ablation can lead to further complications including hematometra and postablation syndrome.
      • McCausland A.M.
      • McCausland V.M.
      Long-term complications of endometrial ablation: cause diagnosis, treatment and prevention.
      Furthermore, pregnancy subsequent to ablation has increased risk of issues such as preterm birth and pathologic adherence of the placenta in the placenta accreta spectrum.
      • Bauer A.M.
      • Hackney D.N.
      • El-Nashar S.
      • et al.
      Pregnancy outcomes after endometrial ablation in a multi-institutional cohort.
      • Kohn J.R.
      • Shamshiraz A.A.
      • Popek E.
      • et al.
      Pregnancy after endometrial ablation: a systematic review.
      Hysterectomy as initial management of menses is also not recommended. The risks of hysterectomy outweigh the benefits especially in light of multiple forms of effective medical management, which are now readily available.
      American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
      However in rare cases, if all options for management of menses have been exhausted and the decision is taken to proceed with surgical management, there needs to be a thorough discussion with patients and guardians about the irreversible nature of hysterectomy, the surgical risk involved with the procedure, and the fact that it will not prevent sexual abuse nor decrease the risk of sexually transmitted infections.
      American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
      In addition, there should be a discussion and careful observation of state laws surrounding sterilization and consent especially in the case in which the patient is a minor or has an intellectual and developmental delay. In addition, discussion with an ethics committee should also be considered before proceeding with surgical procedures for menstrual management.

      Oncology Patients

      Oncology patients represent another unique population who might benefit from menstrual suppression. Although the incidence of a cancer diagnosis in patients ages 15-19 is rare (20 in 100,000), the complications are significant.
      American College of Obstetrics and Gynecology Committee on Adolescent Health Care: ACOG Committee Opinion No. 606. Options for prevention and management of heavy menstrual bleeding in adolescent patients undergoing cancer treatment.
      • Howlader N.
      • Noone A.M.
      • Krapcho M.
      • et al.
      SEER Cancer Statistics Review, 1975-2010.
      Patients are at risk of abnormal uterine bleeding from thrombocytopenia, which might be a result of their cancer or from treatments such as chemotherapy, radiation, or pretreatment regimens for stem cell or bone marrow transplantation.
      • Kirkham Y.A.
      • Ornstein M.P.
      • Aggarwal A.
      • et al.
      Menstrual suppression in special circumstances.
      To avoid risk of heavy bleeding in an already immunocompromised patient population, discussion with patients about menstrual suppression before initiation of treatment plans is advised.
      In a survey of providers in the Pediatric Bone and Marrow Transplant Consortium, GnRH agonists have become the preferred method of menstrual suppression used by pediatric oncologists.
      • Adegite E.A.
      • Goyal R.K.
      • Murray P.J.
      • et al.
      The management of menstrual suppression and uterine bleeding: a survey of current practices in the Pediatric Blood and Marrow Transplant Consortium.
      Short-acting formulations are preferred with the goal of only using the medication when thrombocytopenia (which could lead to heavy menstrual bleeding) is expected. After a transient increase in gonadotropins and estrogen for 2 weeks after initiation, which might lead to increased bleeding, GnRH agonists function as an excellent form of menstrual suppression by inducing a hypoestrogenic state.
      American College of Obstetrics and Gynecology Committee on Adolescent Health Care: ACOG Committee Opinion No. 606. Options for prevention and management of heavy menstrual bleeding in adolescent patients undergoing cancer treatment.
      Leuprolide acetate (LA) is a frequently used GnRH analogue in this population with studies showing 96% amenorrhea rates, but triptorelin has also been used in studies with similar success.
      • Chiusolo P.
      • Salutari P.
      • Sica S.
      • et al.
      Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the prevention of menstrual bleeding in premenopausal women undergoing stem cell transplantation.
      • Meirow D.
      • Rabinovici J.
      • Katz D.
      • et al.
      Prevention of severe menorrhagia in oncology patients with treatment-induced thrombocytopenia by luteinizing hormone-releasing hormone agonist and depo-medroxyprogesterone acetate [erratum in 2007; 110:936].
      With regard to timing, studies have shown starting LA 1 month before planned initiation of treatment yields the lowest rates of failure.
      • Chiusolo P.
      • Salutari P.
      • Sica S.
      • et al.
      Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the prevention of menstrual bleeding in premenopausal women undergoing stem cell transplantation.
      Although this study used a dose of 3.75 mg LA every 28 days with amenorrhea in 29 of 30 patients, other studies have shown similar success rates with different dosing regimens.
      • Laufer M.R.
      • Townsend N.L.
      • Parsons K.E.
      • et al.
      Inducing amenorrhea during bone marrow transplantation. A pilot study of leuprolide acetate.
      • Lhomme C.
      • Brault P.
      • Bourhis J.H.
      • et al.
      Prevention of menstruation with leuprorelin (GnRH agonist) in women undergoing myelosuppressive chemotherapy or radiochemotherapy for hematological malignancies: a pilot study.
      The use of 11.5 mg every 3 months intramuscular injections continues to be popular because of the prolonged period between need for injections, and this medication can also be delivered subcutaneously or intravenously if intramuscular injection is contraindicated.
      • Laufer M.R.
      • Townsend N.L.
      • Parsons K.E.
      • et al.
      Inducing amenorrhea during bone marrow transplantation. A pilot study of leuprolide acetate.
      American College of Obstetrics and Gynecology Committee on Adolescent Health Care: ACOG Committee Opinion No. 606. Options for prevention and management of heavy menstrual bleeding in adolescent patients undergoing cancer treatment.
      Because of the hypoestrogenic state induced by GnRH agonists, if the duration of suppression is expected to be longer than 6 months, add-back therapy should be strongly considered with careful consideration of the risks and benefits.
      • Surrey E.S.
      • Hornstein M.D.
      Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up.
      • DiVasta A.D.
      • Feldman H.A.
      • Sadler Gallagher J.
      • et al.
      Hormonal add-back therapy for females treated with gonadotropin-releasing hormone agonist for endometriosis: a randomized controlled trial.
      • Chwalisz K.
      • Surrey E.
      • Stanczyk F.Z.
      The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis.
      Add-back therapy is commonly conducted with norethindrone acetate 5 mg/d, which has been shown to have positive effects on BMD, decreases in vasomotor symptoms, and decrease of the overall low risk of progesterone-only methods in patients with complex medical conditions.
      • Surrey E.S.
      • Hornstein M.D.
      Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up.
      • DiVasta A.D.
      • Feldman H.A.
      • Sadler Gallagher J.
      • et al.
      Hormonal add-back therapy for females treated with gonadotropin-releasing hormone agonist for endometriosis: a randomized controlled trial.
      • Chwalisz K.
      • Surrey E.
      • Stanczyk F.Z.
      The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis.
      However, combination norethindrone acetate (5 mg/d) and conjugated equine estrogen (0.625 mg/d) add-back appears to be a more effective form of add-back therapy for increasing BMD compared with norethindrone acetate alone.
      • DiVasta A.D.
      • Feldman H.A.
      • Sadler Gallagher J.
      • et al.
      Hormonal add-back therapy for females treated with gonadotropin-releasing hormone agonist for endometriosis: a randomized controlled trial.
      Other medications such as transdermal estrogen can also be options for delivery of estrogen.
      GnRH agonists became popular for use in this population because of thoughts that they might confer some fertility preservation benefit. It is important to keep in mind that although useful in the prevention of menstrual bleeding, the use of GnRH agonists for fertility preservation remains controversial and experimental and thus these medications should not be used for the express purpose of fertility preservation.
      • Oktay K.
      • Harvey B.E.
      • Partridge A.H.
      • et al.
      Fertility preservation in patients with cancer: ASCO clinical practice guideline update.
      • Bildik G.
      • Akin N.
      • Senbabaoglu F.
      • et al.
      GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro.
      • Bai F.
      • Lu Y.
      • Wu K.
      • et al.
      Protecting effects of gonadotropin-releasing hormone agonist on chemotherapy-induced ovarian damage in premenopausal breast cancer patients: a systematic review and meta-analysis.
      • Elgindy E.A.
      • El-Haieg D.O.
      • Horshid O.M.
      • et al.
      Gonadotrophin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial.
      Referral to oncofertility specialist is recommended for patients undergoing gonadotoxic treatment for discussion of fertility preservation options.
      • Oktay K.
      • Harvey B.E.
      • Partridge A.H.
      • et al.
      Fertility preservation in patients with cancer: ASCO clinical practice guideline update.
      Common strategies for menstrual suppression can also be used in oncology patients. The patient’s oncology team might have concerns regarding the use of COCs in this patient population because of the increased risk of venous thromboembolic events as well as liver toxicity in bone marrow and stem cell transplantation patients.
      • Kirkham Y.A.
      • Ornstein M.P.
      • Aggarwal A.
      • et al.
      Menstrual suppression in special circumstances.
      • Hagglund H.
      • Remberger M.
      • Klaesson S.
      • et al.
      Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation.
      • Sica S.
      • Salutari P.
      • Chiusolo P.
      • et al.
      Hormonal therapy after stem cell transplantation and risk of veno-occlusive disease.
      Patients with active malignancy are known to have a 7 times higher risk of developing VTE; however the risk of pregnancy and bleeding requiring transfusion might outweigh the VTE risk depending on the individual patient.
      • Wun T.
      • White R.H.
      Epidemiology of cancer-related venous thromboembolism.
      The US Medical Eligibility Criteria for Contraceptive Use specifically mentions only breast, ovarian, cervical, and endometrial cancers, however, all hormonal contraceptive methods were listed as category 1 or 2 for which there is either no risk or the advantages of using the medication generally outweigh the risks. The exceptions are in breast cancer patients because of concern of hormonally active breast cancer and IUD initiation in cervical and endometrial cancer patients because of concern of seeding with insertion.
      • Curtis K.M.
      • Tepper N.K.
      • Jatlaoui T.C.
      • et al.
      US medical eligibility criteria for contraceptive use, 2016.
      Although there are no large-scale studies in this specific patient population, after a discussion with the patient and their oncology team about risks and benefits, COCs can be used effectively as a form of menstrual suppression. Amsterdam et al in a retrospective chart review of 33 adult patients undergoing bone marrow transplantation reported that 18 patients were receiving some form of COC pill as a first-line treatment for management of heavy menses.
      • Amsterdam A.
      • Jakubowski A.
      • Castro-Malaspina H.
      • et al.
      Treatment of menorrhagia in women undergoing hematopoietic stem cell transplant.
      All but 1 of these patients achieved resolution of their symptoms showing that COCs can be used effectively in this patient population.
      • Amsterdam A.
      • Jakubowski A.
      • Castro-Malaspina H.
      • et al.
      Treatment of menorrhagia in women undergoing hematopoietic stem cell transplant.
      Progesterone-only methods can also be used for menstrual management in this population. DMPA is an option for oncology patients for menstrual suppression during chemotherapy; however, Meirow et al did show that those receiving DMPA had higher rates of needing acute management for bleeding than those receiving GnRH agonists.
      • Meirow D.
      • Rabinovici J.
      • Katz D.
      • et al.
      Prevention of severe menorrhagia in oncology patients with treatment-induced thrombocytopenia by luteinizing hormone-releasing hormone agonist and depo-medroxyprogesterone acetate [erratum in 2007; 110:936].
      Although the use of the levonorgestrel IUD for the management of heavy menses is well established, no specific long-term studies about use of the levonorgestrel IUD have been conducted in this particular population.
      • Adeyemi-Fowode O.A.
      • Santos X.M.
      • Dietrich J.E.
      • et al.
      Levonorgestrel-releasing intrauterine device use in female adolescents with heavy menstrual bleeding and bleeding disorders: single institution review.
      • Lethaby A.
      • Cooke I.
      • Rees M.C.
      Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding.
      However, in a case study it was reported that the continued use of the levonorgestrel IUD during stem cell transplantation resulted without complications of pelvic infection or heavy bleeding even when the patient developed severe pancytopenia.
      • Brady P.C.
      • Soiffer R.J.
      • Ginsburg E.S.
      Continuation of a levonorgestrel intrauterine device during hematopoietic stem cell transplant: a case report.
      Similarly, the etonogestrel implant has also not been studied but it remains a less ideal choice for menstrual suppression because of the known incidence of menstrual irregularity.

      Transgender Patients

      The adolescent transgender and gender nonbinary patient who was assigned female at birth represents another unique patient population who might desire menstrual suppression. For patients who present before the onset of menarche, puberty suppression with the use of GnRH agonists is an option. Working along with a qualified mental health care provider (MHP) with expertise in child and adolescent developmental psychology and psychopathology who can confirm the diagnosis of gender dysphoria/gender nonconformity is essential to assess eligibility for therapy. The Endocrine Society Clinical Practice Guidelines state that if the patient is pubertal (at least Tanner stage 2) puberty suppression can be initiated.
      • Hembree W.C.
      • Cohen-Kettenis P.T.
      • Gooren L.
      Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline.
      If initiated in time, these patients will not experience thelarche or menarche. Subsequently, usually at age 16, with the supervision of a qualified MHP, those who identify as male can choose to initiate testosterone therapy.
      • Hembree W.C.
      • Cohen-Kettenis P.T.
      • Gooren L.
      Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline.
      However, a significant number of patients present after the onset of menarche because puberty and menses can be a moment of initial or increased feelings of gender dysphoria.
      • Crisler J.S.
      • Gorman J.A.
      • Manion J.
      • et al.
      Queer periods: attitudes toward and experiences with menstruation in the masculine of centre and transgender community.
      If these patients are too young to discuss testosterone therapy, have yet to work with a qualified MHP, and desire to avoid monthly menses, initiation of menstrual suppression can be an important step in improving distress due to menses.
      In addition, the desire to keep menstruation controlled in this patient population becomes especially important because transgender patients face issues with safety and access to public restrooms. In a recent survey of transgender and gender nonbinary patients, 66% of participants who are still menstruating reported feeling unsafe or very unsafe using men’s public restrooms.
      • Crisler J.S.
      • Gorman J.A.
      • Manion J.
      • et al.
      Queer periods: attitudes toward and experiences with menstruation in the masculine of centre and transgender community.
      It is therefore not uncommon that patients who have not undergone puberty suppression often present initially for gynecologic care specifically for menstrual suppression. In the same survey, 95% of participants were aware of options for menstrual suppression and 40% had taken medication for menstrual suppression.
      • Crisler J.S.
      • Gorman J.A.
      • Manion J.
      • et al.
      Queer periods: attitudes toward and experiences with menstruation in the masculine of centre and transgender community.
      When discussing options for menstrual management, estrogen-containing hormonal options are often avoided by transgender men because of the feelings of gender dysphoria surrounding the use of an estrogen-containing medication. However, there are no overt medical contraindications to the use of estrogen-containing oral contraceptives. They might often prefer to proceed with progesterone-only oral medications or DMPA injections because these do not require a procedure; however, some patients will decline progesterone-containing methods as well as it is also a “female” hormone. In addition to menstrual suppression, because of its known effect of decreasing estrogen levels, DMPA can also be used in this patient population as a form of puberty suppression if GnRH agonists cannot be obtained because of cost.
      Placement of the levonorgestrel IUD again shows excellent efficacy; however, patient preference plays a key role in the decision to proceed with IUD placement. Some transgender and gender nonbinary patients prefer the idea of not having to take daily medication and if sexually active prefer the increased contraceptive efficacy. Other patients report dysphoria with acknowledging the presence of an IUD. Some patients who do desire the IUD for menstrual suppression will request placement under anesthesia because a pelvic exam can oftentimes be traumatic.
      In addition to the previously mentioned methods, testosterone when initiated in transgender men is another method of menstrual suppression. In a study conducted in Japan of 138 transgender men who took 3 different doses of intramuscular testosterone enanthate ranging from 125 mg every 2 weeks to 250 mg every 2 weeks, cessation of menstruation was noted by 47%-62% in 1 month and by 86%-97% of participants by 6 months of use.
      • Nakmura A.
      • Wantanabe M.
      • Sugimoto M.
      • et al.
      Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder.
      In the study, patients who used 250 mg every 2 weeks had the fastest response of cessation of menses.
      • Nakmura A.
      • Wantanabe M.
      • Sugimoto M.
      • et al.
      Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder.
      Several other studies support this finding that most patients experience cessation of menses 6 months after initiation.
      • Ahmad S.
      • Leinung M.
      The response of the menstrual cycle to initiation of hormonal therapy in transgender men.
      • Deutsch M.B.
      • Bakri V.
      • Kubicek K.
      Effects of cross-sex hormone treatment on transgender women and men.
      These reports also note that high levels of testosterone are not needed to induce menstrual cessation in most patients. A study by Ahmad and Leinung showed that patients who received an average dose of 40.1 (± 8.2) mg/wk of testosterone experienced cessation in 6 months.
      • Ahmad S.
      • Leinung M.
      The response of the menstrual cycle to initiation of hormonal therapy in transgender men.
      Some patients did require higher dose to achieve menstrual cessation; however the average dose was still 56.1 (± 12) mg/wk.
      • Ahmad S.
      • Leinung M.
      The response of the menstrual cycle to initiation of hormonal therapy in transgender men.
      Patients use several different formulations of testosterone; however, in a study of 45 transgender men randomly assigned either intramuscular injection of testovorin-depot, testosterone gel, or intramuscular testosterone undecanoate, time to amenorrhea ranged from 30 to 41 weeks and was not found to differ between the 3 formulations with all participants reporting amenorrhea by 1 year.
      • Pelusi C.
      • Costantino A.
      • Martelli V.
      • et al.
      Effects of three different testosterone formulations in female-to-male transsexual persons.
      It is important that all transgender patients be counseled that although testosterone does function well for menstrual suppression, it does not function as a contraceptive method with reports of pregnancy with concurrent use of testosterone.
      • Light A.D.
      • Obedin-Maliver J.
      • Sevelius J.M.
      • et al.
      Transgender men who experienced pregnancy after female-to-male gender transitioning.
      Patients who are sexually active and report penetrative vaginal intercourse have a chance of unintended pregnancy and should therefore be counseled on contraceptive options.
      • Light A.D.
      • Obedin-Maliver J.
      • Sevelius J.M.
      • et al.
      Transgender men who experienced pregnancy after female-to-male gender transitioning.
      Currently no contraceptive method is contraindicated in patients using cross-sex hormone therapy and although we do not recommend a specific contraceptive method, we highly encourage comprehensive contraceptive counseling including long-acting reversible contraception methods and allowing patients to make an informed decision about their contraceptive options. In addition, unlike progesterone-based medications, testosterone also might not prevent endometrial hyperplasia. A recent study of hysterectomy samples in the transgender men who were receiving testosterone revealed active endometrium in most cases of hysterectomy despite amenorrhea, showing that testosterone might not prevent endometrial hyperplasia.
      • Grimstad F.W.
      • Fowler K.G.
      • New E.P.
      • et al.
      Uterine pathology in transmasculine persons on testosterone: a retrospective multicenter case series.

      Conclusion

      Adolescents require menstrual suppression for a wide array of issues ranging from personal preference to control of chronic pelvic pain to issues with gender dysphoria. In most patients standard counseling can be conducted with use of hormonal contraceptive options as first-line management for patients. However, with special populations additional considerations as well as additional management options need to be discussed to provide the best management of menstrual bleeding.

      References

        • Hillard P.A.
        Menstrual suppression: current perspectives.
        Int J Womens Health. 2014; 6: 631
        • Hee L.
        • Kettner L.O.
        • Vejtorp M.
        Continuous use of oral contraceptives: an overview of effects and side-effects.
        Acta Obstet Gynecol Scand. 2013; 92: 125
        • Wiegratz I.
        • Kuhl H.
        Long-cycle treatment with oral contraceptives.
        Drugs. 2004; 64: 2447
        • Teichmann A.
        • Apter D.
        • Emerich J.
        • et al.
        Continuous, daily levonorgestrel/ethinyl estradiol vs. 21-day, cyclic levonorgestrel/ethinyl estradiol: efficacy, safety and bleeding in a randomized, open-label trial.
        Contraception. 2009; 80: 504
        • Archer D.F.
        • Nakajima S.T.
        • Sawyer A.T.
        • et al.
        Norethindrone acetate 1.0 milligram and ethinyl estradiol 10 micrograms as an ultra low-dose oral contraceptive.
        Obstet Gynecol. 2013; 122: 601
        • Gallo M.F.
        • Nanda K.
        • Grimes D.A.
        • et al.
        20 μg versus >20 μg estrogen combined oral contraceptives for contraception.
        Cochrane Database Syst Rev. 2013; 8: CD003989
        • Scholes D.
        • Ichikawa L.
        • LaCroix A.Z.
        • et al.
        Oral contraceptive use and bone density in adolescent and young adult women.
        Contraception. 2010; 81: 35
        • Baison T.P.
        • Goldberg T.B.L.
        • Kurokawa C.S.
        • et al.
        Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period.
        BMC Endocr Disord. 2015; 15: 15
        • Miller L.
        • Verhoeven C.H.
        • Hout J.I.
        Extended regimens of the contraceptive vaginal ring: a randomized trial.
        Obstet Gynecol. 2005; 106: 473
        • Guazelli C.A.
        • Barreiros F.A.
        • Barbosa R.
        • et al.
        Extended regimens of the vaginal contraceptive ring: cycle control.
        Contraception. 2009; 80: 430
        • Barreiros F.A.
        • Guazzelli C.A.
        • de Araujo F.F.
        • et al.
        Bleeding patterns of women using extended regimens of the contraceptive vaginal ring.
        Contraception. 2007; 75: 204
        • Stewart F.H.
        • Kaunitz A.M.
        • Laguardia K.D.
        Extended use of transdermal norelgestromin/ethinyl estradiol: a randomized trial.
        Obstet Gynecol. 2005; 105: 1389
        • Hubacher D.
        • Lopez L.
        • Steiner M.J.
        • et al.
        Menstrual pattern changes from levonorgestrel subdermal implants and DMPA: systematic review and evidence-based comparisons.
        Contraception. 2009; 80: 113
        • Arias R.D.
        • Jain J.K.
        • Brucker C.
        • et al.
        Changes in bleeding patterns with depot medroxyprogesterone acetate subcutaneous injection 104 mg.
        Contraception. 2006; 74: 234
        • Adeyemi-Fowode O.A.
        • Santos X.M.
        • Dietrich J.E.
        • et al.
        Levonorgestrel-releasing intrauterine device use in female adolescents with heavy menstrual bleeding and bleeding disorders: single institution review.
        J Pediatr Adolesc Gynecol. 2017; 30: 479
        • Rönnerdag M.
        • Odlind V.
        Health effects of long-term use of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use.
        Acta Obstet Gynecol Scand. 1999; 78: 716
        • Hidalgo M.
        • Bahamondes L.
        • Perrotti M.
        • et al.
        Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years.
        Contraception. 2002; 65: 129
        • Grandi G.
        • Farulla A.
        • Sileo F.G.
        • et al.
        Levonorgestrel-releasing intra-uterine systems as female contraceptives.
        Expert Opin Pharmacother. 2018; 19: 677
        • Nelson A.L.
        Levonorgestrel-releasing intrauterine system (LNG-IUS 12) for prevention of pregnancy for up to five years.
        Expert Rev Clin Pharmacol. 2017; 10: 833
        • Nelson A.L.
        LNG-IUS 12: a 19.5 levonorgestrel-releasing intrauterine system for prevention of pregnancy for up to five years.
        Expert Opin Drug Deliv. 2017; 14: 1131
      1. Liletta (levonorgestrel-releasing intrauterine system) [package insert]. Actavis Pharma, Inc, Parsippany, NJ2015
        • Gemzell-Danielsson K.
        • Schellschmidt I.
        • Apter D.
        A randomized, phase II study describing the efficacy, bleeding profile, and safety of two low-dose levonorgestrel-releasing intrauterine contraceptive systems and Mirena.
        Fertil Steril. 2012; 97: 616.e1
      2. Kyleena (levonorgestrel-releasing intrauterine system (19.5) [product monograph]). Bayer Inc, Whippany, NJ2018
        • Altshuler A.L.
        • Hillard P.J.
        Menstrual suppression for adolescents.
        Curr Opin Obstet Gynecol. 2014; 26: 323
        • Molsa P.K.
        Inducement of therapeutic amenorrhea in mentally retarded women: two-year follow-up study.
        Am J Ment Defic. 1986; 90: 591
        • Broome M.
        • Fotherby K.
        Clinical experience with the progestogen-only pill.
        Contraception. 1990; 42: 489
        • Chiusolo P.
        • Salutari P.
        • Sica S.
        • et al.
        Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the prevention of menstrual bleeding in premenopausal women undergoing stem cell transplantation.
        Bone Marrow Transplant. 1998; 21: 821
        • Meirow D.
        • Rabinovici J.
        • Katz D.
        • et al.
        Prevention of severe menorrhagia in oncology patients with treatment-induced thrombocytopenia by luteinizing hormone-releasing hormone agonist and depo-medroxyprogesterone acetate [erratum in 2007; 110:936].
        Cancer. 2006; 107: 1634
        • Laufer M.R.
        • Townsend N.L.
        • Parsons K.E.
        • et al.
        Inducing amenorrhea during bone marrow transplantation. A pilot study of leuprolide acetate.
        J Reprod Med. 1997; 42: 537
        • Lhomme C.
        • Brault P.
        • Bourhis J.H.
        • et al.
        Prevention of menstruation with leuprorelin (GnRH agonist) in women undergoing myelosuppressive chemotherapy or radiochemotherapy for hematological malignancies: a pilot study.
        Leuk Lymphoma. 2001; 42: 1033
        • Surrey E.S.
        • Hornstein M.D.
        Prolonged GnRH agonist and add-back therapy for symptomatic endometriosis: long-term follow-up.
        Obstet Gynecol. 2002; 99: 709
        • DiVasta A.D.
        • Feldman H.A.
        • Sadler Gallagher J.
        • et al.
        Hormonal add-back therapy for females treated with gonadotropin-releasing hormone agonist for endometriosis: a randomized controlled trial.
        Obstet Gynecol. 2015; 126: 617
        • Chwalisz K.
        • Surrey E.
        • Stanczyk F.Z.
        The hormonal profile of norethindrone acetate: rationale for add-back therapy with gonadotropin-releasing hormone agonists in women with endometriosis.
        Reprod Sci. 2012; 19: 563
      3. American college of obstetrics and gynecology committee on adolescent health care: ACOG committee opinion No. 668. Menstrual manipulation for adolescents with physical and developmental disabilities.
        Obstet Gynecol. 2016; 128: e20
        • Kirkham Y.A.
        • Ornstein M.P.
        • Aggarwal A.
        • et al.
        Menstrual suppression in special circumstances.
        J Obstet Gynaecol Can. 2014; 36: 915
        • Grover S.
        Menstrual and contraceptive management in women with intellectual disability.
        Med J Aust. 2002; 176: 108
        • Hornor G.
        • Fischer B.A.
        Child sexual abuse revictimization: child demographics, familial psychosocial factors, and sexual abuse case characteristics.
        J Forensic Nurs. 2016; 12: 151
        • Lavigne J.
        • Sharr C.
        • Elsharkawi I.
        • et al.
        Thyroid dysfunction in patients with Down syndrome: results from a multi-institutional registry study.
        Am J Med Genet A. 2017; 173: 1539
        • Molitch M.E.
        Medication-induced hyperprolactinemia.
        Mayo Clin Proc. 2005; 80: 1050
        • Reimers A.
        • Brodtkorb E.
        • Sabers A.
        Interactions between hormonal contraception and antiepileptic drugs: clinical and mechanistic considerations.
        Seizure. 2015; 28: 66
        • Carl J.S.
        • Weaver S.P.
        • Tweed E.
        • et al.
        Effect of antiepileptic drugs on oral contraceptives.
        Am Fam Physician. 2008; 78: 634
        • Galzote R.M.
        • Rafie S.
        • Teal R.
        • et al.
        Transdermal delivery of combined hormonal contraception: a review of the current literature.
        Int J Womens Health. 2017; 9: 315
        • Cromer B.A.
        • Bonny A.E.
        • Strager M.
        • et al.
        Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study.
        Fertil Steril. 2008; 90: 2060
        • Scholes D.
        • LaCroix A.Z.
        • Ichikaw L.E.
        • et al.
        Change in bone mineral density among adolescent women using and discontinuing depot medroxyprogesterone acetate contraception.
        Arch Pediatr Adolesc Med. 2005; 159: 139
      4. American College of Obstetrics and Gynecology Committee on Adolescent Health Care: ACOG Committee Opinion No. 602. Depot medroxyprogesterone acetate and bone effects.
        Obstet Gynecol. 2014; 123: 1398
        • Bonny A.E.
        • Secic M.
        • Cromer B.
        Early weight gain related to later weight gain in adolescents on depot medroxyprogesterone acetate.
        Obstet Gynecol. 2011; 117: 793
        • Davis A.R.
        • Saadatmand H.J.
        • Pack A.
        Women with epilepsy initiating a progestin IUD: a prospective pilot study of safety and acceptability.
        Epilepsia. 2016; 57: 1843
        • Vieira C.S.
        • Pack A.
        • Roberts K.
        • et al.
        A pilot study of levonorgestrel concentrations and bleeding patterns in women with epilepsy using a levonorgestrel IUD and treated with antiepileptic drugs.
        Contraception. 2019; 99: 251
        • McCausland A.M.
        • McCausland V.M.
        Long-term complications of endometrial ablation: cause diagnosis, treatment and prevention.
        J Minim Invasive Gynecol. 2007; 14: 399
        • Bauer A.M.
        • Hackney D.N.
        • El-Nashar S.
        • et al.
        Pregnancy outcomes after endometrial ablation in a multi-institutional cohort.
        Am J Perinatol. 2018; 35: 931
        • Kohn J.R.
        • Shamshiraz A.A.
        • Popek E.
        • et al.
        Pregnancy after endometrial ablation: a systematic review.
        BJOG. 2018; 125: 43
      5. American College of Obstetrics and Gynecology Committee on Adolescent Health Care: ACOG Committee Opinion No. 606. Options for prevention and management of heavy menstrual bleeding in adolescent patients undergoing cancer treatment.
        Obstet Gynecol. 2014; 124: 397
        • Howlader N.
        • Noone A.M.
        • Krapcho M.
        • et al.
        SEER Cancer Statistics Review, 1975-2010.
        National Cancer Institute, Bethesda, MD2013
        • Adegite E.A.
        • Goyal R.K.
        • Murray P.J.
        • et al.
        The management of menstrual suppression and uterine bleeding: a survey of current practices in the Pediatric Blood and Marrow Transplant Consortium.
        Pediatr Blood Cancer. 2012; 59: 553
        • Oktay K.
        • Harvey B.E.
        • Partridge A.H.
        • et al.
        Fertility preservation in patients with cancer: ASCO clinical practice guideline update.
        J Clin Oncol. 2018; 36: 1994
        • Bildik G.
        • Akin N.
        • Senbabaoglu F.
        • et al.
        GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro.
        Hum Reprod. 2015; 30: 2912
        • Bai F.
        • Lu Y.
        • Wu K.
        • et al.
        Protecting effects of gonadotropin-releasing hormone agonist on chemotherapy-induced ovarian damage in premenopausal breast cancer patients: a systematic review and meta-analysis.
        Breast Care (Basel). 2017; 12: 48
        • Elgindy E.A.
        • El-Haieg D.O.
        • Horshid O.M.
        • et al.
        Gonadotrophin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial.
        Obstet Gynecol. 2013; 121: 78
        • Hagglund H.
        • Remberger M.
        • Klaesson S.
        • et al.
        Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation.
        Blood. 1998; 92: 4568
        • Sica S.
        • Salutari P.
        • Chiusolo P.
        • et al.
        Hormonal therapy after stem cell transplantation and risk of veno-occlusive disease.
        Blood. 1999; 93: 3154
        • Wun T.
        • White R.H.
        Epidemiology of cancer-related venous thromboembolism.
        Best Pract Res Clin Haematol. 2009; 22: 9
        • Curtis K.M.
        • Tepper N.K.
        • Jatlaoui T.C.
        • et al.
        US medical eligibility criteria for contraceptive use, 2016.
        MMWR Recomm Rep. 2016; 65: 1
        • Amsterdam A.
        • Jakubowski A.
        • Castro-Malaspina H.
        • et al.
        Treatment of menorrhagia in women undergoing hematopoietic stem cell transplant.
        Bone Marrow Transplant. 2004; 34: 363
        • Lethaby A.
        • Cooke I.
        • Rees M.C.
        Progesterone or progestogen-releasing intrauterine systems for heavy menstrual bleeding.
        Cochrane Database Systematic Rev. 2005; 4: CD002126
        • Brady P.C.
        • Soiffer R.J.
        • Ginsburg E.S.
        Continuation of a levonorgestrel intrauterine device during hematopoietic stem cell transplant: a case report.
        Anticancer Res. 2017; 37: 1985
        • Hembree W.C.
        • Cohen-Kettenis P.T.
        • Gooren L.
        Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline.
        Endocr Pract. 2017; 23: 1437
        • Crisler J.S.
        • Gorman J.A.
        • Manion J.
        • et al.
        Queer periods: attitudes toward and experiences with menstruation in the masculine of centre and transgender community.
        Cult Health Sex. 2016; 18: 1238
        • Nakmura A.
        • Wantanabe M.
        • Sugimoto M.
        • et al.
        Dose-response analysis of testosterone replacement therapy in patients with female to male gender identity disorder.
        Endocr J. 2013; 60: 275
        • Ahmad S.
        • Leinung M.
        The response of the menstrual cycle to initiation of hormonal therapy in transgender men.
        Transgend Health. 2017; 2: 176
        • Deutsch M.B.
        • Bakri V.
        • Kubicek K.
        Effects of cross-sex hormone treatment on transgender women and men.
        Obstet Gynecol. 2015; 125: 605
        • Pelusi C.
        • Costantino A.
        • Martelli V.
        • et al.
        Effects of three different testosterone formulations in female-to-male transsexual persons.
        J Sex Med. 2014; 11: 3002
        • Light A.D.
        • Obedin-Maliver J.
        • Sevelius J.M.
        • et al.
        Transgender men who experienced pregnancy after female-to-male gender transitioning.
        Obstet Gynecol. 2014; 124: 1120
        • Grimstad F.W.
        • Fowler K.G.
        • New E.P.
        • et al.
        Uterine pathology in transmasculine persons on testosterone: a retrospective multicenter case series.
        Am J Obstet Gynecol. 2019; 220: 257.e1