9/13/2018

Pediatric Pharmacy Advocacy Group

Missing Menses: Preventing the Menstrual Cycle and Emergent Therapy for Breakthrough Bleeding

Tara Wright, PharmD, BCPPS Seattle Children’s Hospital

Objectives

• Identify gynecologic concerns in adolescent females undergoing cancer therapy • Summarize supportive care recommendations for a patient receiving leuprolide acetate • Discuss pros and cons of preventative therapies for menstrual suppression • Recognize therapies that can be utilized for emergent management of breakthrough bleeding

Audience Experience

• My institution has a guideline for managing menstrual suppression

• I manage menstrual suppression regimens regularly

1 9/13/2018

Terminology

Term Definition

Amenorrhea No bleeding for ≥ 6 months in a nonmenopausal woman

Menorrhagia Heavy regular menstrual cycles with heavy bleeding of > 80 mL or a duration of > 7 days Menometrorrhagia Excessive menstrual bleeding at regular intervals

Metrorrhagia Bleeding between periods or irregular bleeding

Oligomenorrhea occurring at intervals > 35 days apart

Polymenorrhea Menstrual bleeding occurring at intervals < 21 days apart

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110.

Abnormal Uterine Bleeding (AUB)

• Change in menstrual cycle, amount of blood loss, duration of flow, or menses frequency

• AUB can significantly alter quality of life – 10-30% of women experience menorrhagia

• 20% of ambulatory care visit due to issues

• Among adolescents, 34-51% report experiencing oligomenorrhea and polymenorrhea

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Nicholson WK. Am J Obstet Gynecol. 2001; 184:523-30. Rigon F. Italian Journal of Pediatrics. 2012;38:38.

Cancer and AUB

• Diagnosis of cancer in females aged 15-19 years – 20 cases per 100,000 individuals per year • Cancer therapy and uterine toxicity – Radiation • Effects vary by site and dose – • Gonadotoxicity influenced by age and type of treatment • Hormonal disturbance and dysfunctional uterine bleeding – Surgery • Site of surgery and organs removed may affect fertility

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Centers for disease control and prevention. MMWR recomm Rep. 2010;59(RR-1):1-86. Obstet Gynecol. 2014;124(2):403-408.

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Gynecologic Concerns

• Pubertal development • and anemia • Contraception • Ovarian insufficiency • Breast and cervical cancer screening • Fertility • Pregnancy outcomes

Obstet Gynecol. 2014;124:397-402.

Complications in Oncology Patients

Increased Worsening Increased transfusion thrombocytopenia morbidity requirement

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Meirow D, et al. Cancer. 2006;107(7):1634-1641. Obstet Gynecol. 2014;124:397-402. Shipman C. JHOP. 2015;5(3):70-73.

Menstrual Cycle

https://medium.com/@bicspuc/menstrual-cycle-an-important-process-of-human-reproduction-e22a4abce2e2

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110.

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Hormone regulation of the Menstrual Cycle

GnRH = gonadotropin release hormone; FSH = follicle stimulating hormone; LH = luteinizing hormone

Hawkins S, et al. Ann N Y Acad Sci. 2008;1135:10-18. Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110.

Preventative Therapy

• Goal: prevention of menorrhagia – severe cause of significant morbidity

• Therapy Options 1) Estrogen/progestin oral contraceptive pills (OCP) 2) Transdermal system 3) Progestin only (various dosage forms) • Intramuscular/oral medroxyprogesterone acetate • Norethindone acetate 4) Gonadotropin-releasing hormone (GnRH) agonist • Leuprolide acetate

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402. Shipman C. JHOP. 2015;5(3):70-73.

Prevention of Heavy Menstrual Bleeding (HMB)

Quinn S, et al. Curr Opin Pediatr. 2016;28:421-427.

4 9/13/2018

Preventative Therapy Considerations

What to think about when choosing best option:

Ability to take oral medications

Patients’ risk of thromboembolism

Contraindication to intramuscular (IM) injections

Need for contraception

Ovarian preservation

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402. Oktay K, et al. J Clin Oncol. 2018;36:1994-2001. Shipman C. JHOP. 2015;5(3):70-73.

GONADOTROPIN RELEASING HORMONE AGONIST

GnRH Agonist

• Leuprolide acetate is a synthetic GnRH agonist

• Mechanism – Prolonged exposure results in desensitization of GnRH receptors – Decrease in synthesis and secretion of LH and FSH

• Generally considered agent of choice due to consistent ability to lead to amenorrhea – Lower failure rates observed when started at least 2 weeks prior to onset of thrombocytopenia

• 73-96% reduction in menstrual blood flow – Flare-bleeding may occur during the first 2-3 weeks after injection

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402. Quaas A, et al. Eur J Obstet Gynecol Reprod Biol. 2007;134:3-8 Shipman C. JHOP. 2015;5(3):70-73.

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Leuprolide Options

Drug Dosing Side effects

Lupron Depot® 3.75 mg IM monthly Hot flashes, night sweats, mood swings, bone mineral density loss with use > 6 months, potential Lupron Depot® – 3 month 11.25 mg IM q 3 months benefit on fertility preservation

Considerations • Clinical: ↓ injecons during thrombocytopenic state with 3 month depot

• Cost: no significant difference between 1 month and 3 month depot

• Safety: multiple products on formulary  confusion when prescribing/dispensing

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Leuprolide acetate. Lexi-comp™. Accessed August 1, 2018. Obstet Gynecol. 2014;124:397-402.

Leuprolide Literature

Study Methods Results Notes Sica S, et al. AML (n = 16) -No difference in frequency, duration of Both groups experienced (1996) bleeding or transfusion support. vaginal bleeding cessation; OCP vs. OCP (16 days) + leuprolide induced longer Prospective leuprolide 3.75 mg SQ q28 days - OCP only group: ↑ vaginal bleeding aer last amenorrhea stopping OCP in OCP group (p = 0.009)

-OCP only group: grade III-IV liver toxicity Lhomme C, et al. Hematologic malignancy, age 18- -85% of women had no clinically relevant Increased risk of (2001) 48 years (n = 21) vaginal bleeding osteoporosis observed if leuprolide use >6 months Prospective Nomegestrol acetate 5 mg/day -67% of the severe bleeding events on days 1-35 + leuprolide 3.75 occurred after the first leuprolide dose Supports need for mg SQ q28 days (flare effect) progestin therapy past second leuprolide injection Meirow D, et al. No treatment (n = 20) Rates of bleeding: No difference in inducing (2006) vs. -No treatment - 65% amenorrhea between DMPA 150 mg IM q3 mo (n = 42) -DMPA - 55% treatment groups vs. -Leuprolide - 23% Retrospective leuprolide 3.75 mg IM q28 days Higher rates of bleeding (n = 39) Moderate to severe bleeding: with DMPA vs. leuprolide -No treatment – 40% -DMPA – 21.4% -Leuprolide – 0%

Lhomme C, et al. Leuk Lymph. 2001;42:1033-41. Meirow D, et al. Cancer. 2006;107:1634-41. Sica S, et al. Am J Hematol. 1996;51:248-9.

GnRH Agonists Considerations

• Hypoestrogenic state can lead to vasomotor symptoms and bone density loss – Hormonal add-back therapy can preserve bone mass and reduce vasomotor symptoms • Norethindrone acetate 5 mg PO daily or • OCP (e.g. EE/norethindrone 0.03 mg/1.5 mg PO daily)

• Potential benefit on fertility preservation – Conflicting data; should not be used in place of proven fertility preservation methods

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Oktay K, et al. J Clin Oncol.2018;36:1994-2001.

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Bone Density and GnRH Agonists

• Adolescence is a critical time period for accrual of bone mineral density (BMD) • GnRH agonists increase bone turnover and possible prevent attainment of peak BMD in adolescents • Occurs with prolonged exposure (>6 months) – Potentially irreversible – Therapy restricted to 6 months vs. period of duration of myelosuppressive chemo

DiVasta A, et al. J Pediatr Adolesc Gynecol. 2007;20(5):293-297. Surrey E, et al. Obstet Gynecol. 2002;99(5):709-719. Taga M, et al. Acta Obset Gynecol Scand. 1996;75:162-165.

Managing Bone Health

• Education and awareness among all providers

• Calcium and vitamin D monitoring & supplementation

• Consider utility of DEXA scan

• Add back therapy with norethindrone acetate

Vitamin D Monitoring

• 25-hydroxy vitamin D levels (every 3-6 months) – Normal: > 30 ng/mL – Insufficient: 16-30 ng/mL – Deficient: 5-15 ng/mL – Severely deficient: < 5 ng/mL

• Supplementation – Calcium (1200-1500mg daily) – Vitamin D (400-800IU daily)

• Consider DEXA scans

Kaya A, et al. West Indian Med J. 2015;64(2):104-107. Kidney International. 2009. 76 (Suppl 113), S9–S2. Mitwally M, et al. Menopause. 2002;9(4):236-241.

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Lupron Add-back Study Group

• Hornstein M, et al (1998) – Purpose: evaluate the efficacy and safety of leuprolide acetate alone and in combination with hormonal add- back therapy – Methods: all patients received IM leuprolide with add- back therapy • Group A: placebo for progestin and estrogen • Group B: norethindrone acetate 5 mg daily and placebo for estrogen • Group C: norethindrone acetate 5 mg daily and conjugated estrogens 0.625 mg daily • Group D: norethindrone acetate 5 mg daily and conjugated estrogens 1.25 mg daily

Hornstein, et al. Obstet Gynecol. 1998;91:16-24.

Bone Mineral Density (BMD) Results

Group A Group B Group C Group D (placebo) (progestin + (progestin + (progestin + placebo) estrogen) higher dose estrogen)

BMD (g/cm2)

Baseline 1.030 ± 0.111 1.030 ± 0.128 1.060 ± 0.113 1.044 ± 0.121

Week 24 1.016 ± 0.113 1.046 ± 0.130 1.052 ± 0.108 1.057 ± 0.128

Week 52 0.988 ± 0.097 1.044 ± 0.137 1.051 ± 0.112 1.062 ± 0.132

Hornstein, et al. Obstet Gynecol. 1998;91:16-24.

Vasomotor Symptoms Results

Group A Group B Group C Group D (placebo) (progestin + (progestin + (progestin + placebo) estrogen) higher dose estrogen) % with hot 88 47 58 40 flashes Median days of 28 0 2 0 hot flashes Median maximum # of 6010 hot flashes in 24 hours

Hornstein, et al. Obstet Gynecol. 1998;91:16-24.

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Lupron Add-back Follow-up • Surrey E, et al (2002) – Purpose: assess post-treatment effects of a 12 month course of leuprolide alone or with hormonal add-back therapy – Methods: all patients received IM leuprolide with add-back therapy – Group A: placebo for progestin and estrogen – Group B: norethindrone acetate 5 mg daily and placebo for estrogen – Group C: norethindrone acetate 5 mg daily and conjugated estrogens 0.625 mg daily – Group D: norethindrone acetate 5 mg daily and conjugated estrogens 1.25 mg daily lumbar spine BMD and physical symptoms evaluated at 12 and 24 months post-therapy

Surrey E, et al. Obstet Gynecol. 2002;99(5):709-719.

Follow-up Results

Percent change in bone mineral density from baseline

Group A Group B Group C Group D (placebo) (progestin + (progestin + (progestin + placebo) estrogen) higher dose estrogen) Mean ± SEM percent change from baseline Final treatment -5.4 ± 0.71 -1.2 ± 0.7 -0.2 ± 0.63 0.5 ± 0.69 8 month post -3.4 ± 0.66 -0.9 ± 0.6 0.2 ± 0.58 0.6 ± 0.62 12 month post -2.3 ± 0.62 -0.7 ± 0.67 0.8 ± 0.64 0.5 ± 0.62 16 month post -1.9 ± 0.98 -0.03 ± 1.05 1.2 ± 0.78 2.3 ± 0.87 20 month post -2.1 ± 0.91 0.14 ± 0.89 0.3 ± 0.91 1.6 ± 1.06 24 month post -0.9 ± 1.29 1.5 ± 0.95 1.2 ± 1.1 0.9 ± 1.18

Surrey E, et al. Obstet Gynecol. 2002;99(5):709-719.

Lupron Add-back Study Conclusion

• Leuprolide can safely be extended to 12 months of use

• Leuprolide and norethindrone acetate ± low-dose estrogen preserves bone mineral density during and post completion of therapy

• Leuprolide and norethindrone acetate ± low-dose estrogen results in decrease of vasomotor symptoms

Hornstein, et al. Obstet Gynecol. 1998;91:16-24. Surrey E, et al. Obstet Gynecol. 2002;99(5):709-719.

9 9/13/2018

Leuprolide Counseling Points

• Should not be utilized as contraception

• Vasomotor symptoms including hot flashes and night sweats – Add back therapy can help manage symptoms

• Effects on bone health – Add back therapy shown to preserve BMD

• Conflicting data on fertility preservation

ORAL CONTRACEPTIVE PILLS

Oral Contraceptive Pills (OCP)

• Mechanism – Induces negative feedback loop on – Estrogen suppresses production of FSH, preventing follicular maturation – Progesterone prevents the surge of LH, leading to anovulation • Prevents withdrawal bleeding leading to amenorrhea – Contiguous hormone exposure maintains suppression of LH and FSH

• ~43% reduction in menstrual blood flow

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Bradley L, et al. Am J Obstet Gynecol. 2016;31-43. Shipman C. JHOP. 2015;5(3):70-73.

10 9/13/2018

OCP Options

 Estrogen/progestin products

Examples Dosing Side effects Oral Ethinyl / drospirenone 0.03 mg/3 mg PO daily* Mild: nausea, vomiting, (Ocella®) breast tenderness Ethinyl Estradiol/ norgestimate 0.035mg/0.25 mg PO daily* Serious: thrombosis, (Ortho-cyclen® 28) hypertension, hepatotoxicity Ethinyl Estradiol/ norethindrone 0.03 mg/1.5 mg PO daily* (Loestrin® 21 1.5/30) CYP3A4 inducers will ↓ efficacy of OCPs Patch Norelgestromin and ethinyl 1 patch every 7 days Black Box Warning: estradiol (Xulane®) increased risk of VTE compared to OCP *Continuous (not cyclic) dosing

Bradley L, et al. Am J Obstet Gynecol. 2016;31-43. Contraceptive comparison table. Lexi-comp™. Accessed August 7,2018. Jacobson JC, et al. J Midwifery Womens Health. 2012;57:585-592. Shipman C. JHOP. 2015;5(3):70-73.

Continuous vs. Cyclic OCP

Study Study Group Results Conclusion Miller, 2003 Healthy women 18-45 Amenorrhea • Adverse events similar years of age (continuous OCP; n = in both groups Purpose: 37): compare Continuous (no • 68% during cycles 1– • Continuous OCP use bleeding placebo pills) 3 associated with profiles of vs. • 88% during cycles significantly fewer cyclic vs. Cyclic (placebo pills) 10–12 bleeding days continuous administration OCP: 20 mcg ethinyl Amenorrhea (cyclic • Note: no equivalent of estradiol/100 mcg OC; n = 36): study in adolescent contraceptives levonorgestrel • 0% during cycles 1–3 population • 11% during cycles 10–12

OCP = oral contraceptive pill

Miller L, et al. Obstet Gynecol. 2003;101:653-661.

Disadvantages to OCP

Poor medication adherence

Erratic Absorption

Hepatotoxicity

Venous thromboembolism (VTE)

Bradley L, et al. Am J Obstet Gynecol. 2016;31-43. Obstet Gynecol. 2014;124:397-402. Quinn S, et al. Curr Opin Pediatr. 2016;28:421-427. Shipman C. JHOP. 2015;5(3):70-73.

11 9/13/2018

Hepatotoxicity and OCPs

• OCPs associated with several liver related complications – cholestasis, sinusoidal dilatation, hepatic adenomas, hepatocellular carcinoma, hepatic venous thrombosis, and increase risk of gallstones • OCPs undergo first-pass hepatic metabolism – Consider switching to a transdermal patch (Xulane® 0.035/0.15 mg/24 hours; q7 days)

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402. Shipman C. JHOP. 2015;5(3):70-73.

Venous Thromboembolism (VTE) Risk

Burkman R, et al. Am J Obstet & Gyn. 2004;190:5-22.

Risk Factors for VTE • Risk factors – Estrogen dose • highest risk with doses > 50 mcg/day – Increased risk during first year – Age – Type of progestin • Levonorgesterol lower risk than drosperinone and desogestrel – History of VTE • WHO guidelines: OCPs unacceptable risk for patients with active or history of DVT – Superficial venous thromboembolism: risk may outweigh benefits – Transdermal system • Steady state EE concentrations is ~60% higher and may increase the risk of VTE rates when compared with OCP

Frieden T, et al. MMWR Recomm Rep 2016;65(4):1-66. Lidegaard O, et al. BMJ. 2009;339:b2890.

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Contraindications to Estrogen Use

• History of estrogen-dependent tumor • Active or history of deep vein thrombosis • History of stroke • ≥35 years of age + ≥15 cigarettes/day • Multiple risk factors for cardiovascular disease* • Active liver disease • Migraine with aura

Frieden T, et al. MMWR Recomm Rep 2016;65(4):1-66.

PROGESTIN ONLY

Progestin

• Mechanism – Inhibits ovulaon and leads to ↓ secreon of FSH and LH, altering endometrial proliferation

• Less side effects than combined OCPs (lack of estrogen) – Bleeding can be unpredictable

• ~32-50% reduction in menstrual blood flow

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402. Shipman C. JHOP. 2015;5(3):70-73.

13 9/13/2018

Progestin Only Options

• Injectable and oral products

Drug Dosing Side effects Medroxyprogesterone IM: 150 mg every 12 weeks acetate Bloating, weight gain, PO: 2.5-10 mg daily acne, nausea, hirsutism, Norethindrone acetate 5 mg by mouth daily unpredictable bleeding

*If already implanted prior Levonorgesterol IUD: Infection with to diagnosis, may be intrauterine device insertion/during appropriate to continue for (IUD) neutropenia menstrual suppression

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402.

Survey of Current Practices in the Pediatric Blood and Marrow Transplant Consortium

Adegite E, et al. Pediatr Blood Cancer. 2012;59:553-557.

Drug Dosing Side effects Lupron Depot® 3.75 mg IM monthly Hot flashes, night sweats, mood 11.25 mg IM Q 3 months swings, BMD loss, potential benefit on fertility preservation Progestin only Medroxyprogesterone IM: 150 mg every 12 weeks acetate PO: 2.5-10 mg daily Bloating, weight gain, acne, nausea, hirsutism, unpredictable bleeding Norethindrone acetate 5 mg by mouth daily IUD: Infection with insertion/during *If already implanted prior to diagnosis, Levonorgesterol neutropenia may be appropriate to continue for intrauterine device (IUD) menstrual suppression Estrogen/progestin oral contraceptive pills (OCP)

Mild: nausea, vomiting, breast Various products tenderness 1 tablet by mouth daily Serious: thrombosis, hypertension, hepatotoxicity

Transdermal Patch Norelgestromin and ethinyl estradiol Black Box Warning: increased risk of 1 patch every 7 days (Xulane®) VTE compared to OCP

14 9/13/2018

Audience Participation Question

• Which of the following side effects has been reported with leuprolide acetate?

A. Breast tenderness B. Thromboembolism C. Transaminitis D. Hot flashes

Patient Case

• KS is a 16 y/o with HR • CBC pre-B ALL, currently in – WBC: 2,550 cells/mm3 delayed intensification – HGB: 8.5 g/dL – HCT: 26.8 % • She has a serious – PLT: 11,000 cells/mm3 boyfriend and reports – ANC: 800 cells/mm3 being sexually active • Liver Panel • She is taking ethinyl – AST: 402 U/L estradiol/ norethindrone – ALT: 630 U/L 0.03 mg/1.5 mg PO daily – T. bili: 0.2 mg/dL – GGT: 307 U/L

Audience Participation Question

• Upon review you note KS has up trending LFTs and you want to adjust her menstrual suppression regimen. What is the best option for menstrual suppression for KS?

A. Continue on current OCP B. Change to leuprolide 11.75 mg IM Q 3 months C. Change to a transdermal patch (Xulane Q 7 days) D. Change to DMPA 3.75 mg IM monthly

15 9/13/2018

ACUTE UTERINE BLEEDING MANAGEMENT

Breakthrough Bleeding

• Spotting or light bleeding – No intervention necessary if patient clinically stable

• Moderate - heavy bleeding – Intervention depends on preventative therapy already initiated

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402.

Management of Heavy Menstrual Bleeding (HMB)

Quinn S, et al. Curr Opin Pediatr. 2016;28:421-427.

16 9/13/2018

Breakthrough Bleeding Management

Leuprolide OCPs Progestin only Mild bleeding or No intervention if patient clinically stable spotting Norethindrone acetate Double the dose of DMPA: addition of taper (ex: 15 mg x 5 days, OCP until OCP 10 mg x 5 days, 5 mg amenorrhea daily) Oral: norethindrone Moderate to severe OR acetate taper (ex: 15 bleeding Medroxyprogesterone mg x 5 days, 10 mg x 5 acetate (40mg BID x 5 days, 5 mg daily) days, 20mg BID x 5 days, 10mg BID x 5 days, 10mg daily x 5 days) -addition of OCP until -change to OCP with -consider adding amenorrhea higher potency leuprolide Persistent bleeding -addition of hormonal hormones patch -add leuprolide

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402.

Menorrhagia

• May be present at time of diagnosis if thrombocytopenic

• Mild-moderate vs. severe bleeding – Can occur in the absence of preventive therapy – Can occur despite appropriate preventative measures

Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402.

Treatment Options

• Antifibrinolytics – Tranexamic acid: 1,300 mg PO 3 times daily (max: 3900 mg/day) – Aminocaproic acid: 50-100 mg/kg/dose IV/PO every 6 hours (max: 24g/day)

• Blood products – Fresh frozen plasma • factors II, V, VII, IX, X, and XI, fibrinogen, protein C and S – Cryoprecipitate • fibrinogen, von Willebrand factor, factor VIII, factor XIII – Packed RBCs – Platelets • Set threshold: 20,000-50,000 cells/mm3

• Hormones – Ex: Medroxyprogesterone: 60-120 mg x 1 day, 20 mg daily x 10 days

Aksu F, et al. Aust N Z J Obstet Gynaecol. 1997;37:228-231. Aminocaproic acid. Lexi-comp™. Accessed August 30, 2018. Bates JS, et al. Pharmacotherapy. 2011;31:1092-1110. Obstet Gynecol. 2014;124:397-402. Shipman C. JHOP. 2015;5(3):70-73. Tranexamic acid. Lexi-comp™. Accessed August 30, 2018.

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ACOG Proposed Algorithm

Obstet Gynecol. 2014;124:397-402.

Patient case

• AB is a 14 year old female with PMH of Ewing sarcoma • During consolidation week 3 of IE, Day 4, AB reports using 3-4 pads per day x 2 days. Platelets today are 8,000 cells/mm3 • AB received her first dose of leuprolide 1 week prior to admission and reports compliance with her daily norethindrone acetate 5 mg daily

Audience Participation Question

What is the most likely cause of breakthrough bleeding in this scenario?

A: Leuprolide is not as effective as other options for reducing menstrual bleeding B: It’s a common side effect of norethindrone C: Leuprolide flare effect D: Thrombocytopenia

18 9/13/2018

Audience Participation Question

• The team asks you what you for a recommendation regarding AB’s breakthrough bleeding. Which of the following is the best option for AB?

A. Increase norethindrone acetate to 15 mg daily B. Administer another dose of leuprolide C. Add estrogen-containing OCP D. Add DMPA injection

Take-Home Points

• Appropriately managing menstrual suppression therapy is paramount in maintain quality of life

• Ensure approximate supportive care management specific to therapy used for menstrual suppression

• Prevention and emergent therapy should be individualized for each patient based on risk factors and contraindications

Missing Menses: Preventing the Menstrual Cycle and Emergent Therapy for Breakthrough Bleeding

Tara Wright, PharmD, BCPPS Seattle Children’s Hospital

19