Course Director, Elizabeth A. Stewart, MD, prepared useful Practice Aids pertaining to uterine fibroids and endometriosis for this CME activity titled "Advances in Medical Options for Uterine Fibroids and Endometriosis: Clinical Highlights From Montreal." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2HY3HDz. CME credit will be available until June 24, 2020.

1. Access the activity, “Advances in Medical Options for Uterine Fibroids and
Endometriosis: Clinical Highlights From Montreal,” at PeerView.com/NNZ40.
Medical Management
and Classification of
Uterine Fibroids
PRACTICE AID
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Planning pregnancy
in future
• Hormonal
contraceptives or
tranexamic acid
• Reevaluate in 1 y,
or sooner if
symptoms worsen
When patient is
ready for pregnancy,
reassess for risk
factors for infertility
and possible need for
additional fibroid
treatment
Not planning pregnancy
in future
• First-line therapy: Hormonal
contraceptives, endometrial
ablation, tranexamic acid
• Reevaluate in 1 y, or sooner
if symptoms worsen
• Consider hysterectomy if
there is inadequate response
to first-line therapy, other
intercurrent disease that is
responsive to hysterectomy,
new fibroids that develop after
initial treatment success, or if
patient elects hysterectomy
after comprehensive counseling
Wishes to become
pregnant now
Severe symptoms
• Complete fertility
evaluation
• Consider
myomectomy or
other uterine-sparing
treatment with
counseling regarding
risks to fertility if no
other reason for
infertility is identified
Mild symptoms
• Advise patient to attempt
pregnancy for 6 mo
• If not pregnant, complete
fertility evaluation
• Consider myomectomy or
other uterine-sparing
treatment with counseling
regarding risks to fertility
if no other reason for
infertility is identified
Women with heavy menstrual bleeding only
Type 0 or 1
fibroids
All other types
of fibroids
Hysteroscopic
myomectomy
Women with bulk symptoms with or without heavy menstrual bleeding
Wishes to become
pregnant now
Severe symptoms
• Complete fertility
evaluation
• Consider myomectomy
or other uterine-sparing
treatment with
counseling regarding
risks to fertility if no other
reason for infertility is
identified
Mild symptoms
• Advise patient to attempt
pregnancy for 6 mo
• If not pregnant, complete fertility
evaluation
• Consider myomectomy or other
uterine-sparing treatment with
counseling regarding risks to
fertility if no other reason for
infertility is identified
Planning future pregnancy
(in 2 to ≤5 y or >5 y)
• ≤5 y: Medical therapy
(progesterone-receptor
modulator or GnRH agonist
with low-dose estrogen,
progesterone, or both)
• >5 y: Myomectomy or MRI-guided
FUS, or UAE or radio-frequency
ablation with counseling
regarding risks to fertility
When patient is ready for
pregnancy, reassess for risk
factors for infertility and
possible need for additional
fibroid treatment
Not planning pregnancy in future
Assess time to menopause
(≤5 y or >5 y)
• ≤5 y: Medical therapy vs UAE,
MRI-guided FUS, or radio-
frequency ablation or
hysterectomy if there is
inadequate response to first-line
therapy, other intercurrent
disease that is responsive to
hysterectomy, new fibroids that
develop after initial treatment
success, or if patient elects
hysterectomy after
comprehensive counseling
• >5 y: Hysterectomy vs UAE,
MRI-guided FUS, or radio-
frequency ablation
Medical Management of Uterine Fibroids—With HMB1
Medical Management of Uterine Fibroids—With Bulk Symptoms With or Without HMB1

2. Access the activity, “Advances in Medical Options for Uterine Fibroids and
Endometriosis: Clinical Highlights From Montreal,” at PeerView.com/NNZ40.
Medical Management
and Classification of
Uterine Fibroids
PRACTICE AID
FUS: focused ultrasound surgery; GnRH: gonadotropin-releasing hormone; HMB: heavy menstrual bleeding; UAE: uterine artery embolization.
1. Stewart EA. N Engl J Med. 2015;372:1646-1655. 2. Munro MG. Understanding the Clinical Impact: Addressing Evidence Gaps in Adenomyosis, Endometriosis, and Uterine Fibroids. Society of
Endometriosis and Uterine Disorders Congress 2019 (SEUD 2019).
Leiomyoma Subclassification System2
SM:
Submucous
0 Pedunculated intracavitary
1 <50% intramural
2 ≥50% intramural
Contacts endometrium; 100% intramural
O:
Other
4 Intramural
5 Subserous ≥50% intramural
6 Subserous <50% intramural
7 Subserous pedunculated
8 Other (specify; eg, cervical, parasitic)
Hybrid
(Contact both the
endometrium and
the serosal layer)
2 numbers are listed, separated by a hyphen. By convention, the first
refers to the relationship with the endometrium while the second refers
to the relationship in the serosa. One example is below.
2-5
Submucous and subserous, each with less than
half the diameter in the endometrial and
peritoneal cavities, respectively
2-5
3 4
6 2
7
8
5
1
0
3

3. Access the activity, “Advances in Medical Options for Uterine Fibroids and
Endometriosis: Clinical Highlights From Montreal,” at PeerView.com/NNZ40.
Medical Management
of Endometriosis and
Endometriosis-Associated Pain
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
GnRH: gonadotropin-releasing hormone; SERM: selective estrogen receptor modulator; SPRM: selective progesterone receptor modulator.
1. Giudice LC. N Engl J Med. 2010;362:2389-2239. 2. Munro MG. Understanding the Clinical Impact: Addressing Evidence Gaps in Adenomyosis, Endometriosis, and Uterine Fibroids. Society of
Endometriosis and Uterine Disorders Congress 2019 (SEUD 2019). 3. Petraglia F. Plenary on Endometriosis: From Bench to Bedside. SEUD 2019.
PRACTICE AID
First-
Line
• NSAIDs1
• Cyclic combined oral contraceptives (estrogen + progestin)1,2
Second-
Line
• Continuous combined oral contraceptives1,2
• Medroxyprogesterone acetate1,2
• Levonorgestrel intrauterine system1,2,a
• GnRH agonists ± add-back therapy1,2
• GnRH antagonists ± add-back therapy2
• Danazol1,2
Third-
Line
• Aromatase inhibitors1,a
Medical treatment preferred3
:
• In women of reproductive age in pain and no desire for pregnancy
• When surgery is contraindicated
• When patient refuses surgery due to previous surgical experiences
• To prevent or treat recurrence
Reduce estrogen
sensitivity
GnRH
antagonists
Aromatase
inhibitors
SERMs
Reduce
progesterone
resistance
SPRMs
Reduce
inflammation/pain
Monoclonal
antibodies
Prostaglandin
receptor
antagonists
Reduce peritoneal
invasion/
neuroangiogenesis
Dopamine
agonists
New Strategies for Endometriosis Management3
First-, Second-, and Third-Line Strategies for Endometriosis Management1
a
Not US FDA–approved for this indication.

4. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Treatment Options for Endometriosis-Associated
Pain and Uterine Fibroids—Insights From SEUD 2019
PRACTICE AID
Access the activity, “Advances in Medical Options for Uterine Fibroids and Endometriosis:
Clinical Highlights From Montreal,” at PeerView.com/NNZ40.
Medication
Class
Agent
Study Name/
Phase
Key Findings
GnRH analogue Triptorelin Noninterventional study1
• Pelvic pain, ovulation pain, and dyspareunia were reduced by mo 3 and
maintained through mo 24
• Dysmenorrhea increased from 9.5% at 12 mo to 15.4% at 24 mo
GnRH antagonist
Elagolix
ELARIS EM-1 and
ELARIS EM-2
Phase 32,3
• Higher percentage of patients on elagolix experienced reduction in pain and
had decreased or stable use of rescue analgesic agents
• At mo 6, 75.3% women receiving elagolix 200 mg BID and 42.1% receiving
elagolix 150 mg QD vs 23.1% receiving placebo had dysmenorrhea
• Reduction in nonmenstrual pelvic pain was observed in 62.1% of women
receiving elagolix 200 mg BID and 45.7% receiving elagolix 150 mg QD
vs 34.9% receiving placebo
Linzagolix
EDELWEISS
Phase 2b4
• Dose-dependent reductions in serum estradiol levels and endometriosis-
associated pelvic pain observed at 12 wk
– For doses ≥75 mg, titration did not increase benefit
– 200-mg dose suppressed estradiol to postmenopausal levels
– Effects were maintained or increased at 24 wk
Relugolix
Phase 2 study2
• Once-daily oral relugolix was noninferior to monthly leuprorelin injection in
endometriosis management
• Greatest benefit in decrease in pelvic pain was observed at the highest dose
of 40 mg QD
SPIRIT 1, SPIRIT 2, and
SPIRIT EXTENSION
Phase 35-7
• Ongoing randomized, placebo-controlled trials assessing relugolix 40 mg QD
in combination with low-dose estradiol and norethindrone acetate for 24 wk
(SPIRIT 1 and SPIRIT 2) or up to 104 wk (SPIRIT EXTENSION) in women
with endometriosis-associated pain
• Primary endpoint: Proportion of patients with dysmenorrhea and nonmenstrual
pelvic pain
• Anticipated N = 600 in SPIRIT 1 and SPIRIT 2; 800 in SPIRIT EXTENSION
Agents in Endometriosis-Associated Pain

5. Treatment Options for Endometriosis-Associated
Pain and Uterine Fibroids—Insights From SEUD 2019
PRACTICE AID
Access the activity, “Advances in Medical Options for Uterine Fibroids and Endometriosis:
Clinical Highlights From Montreal,” at PeerView.com/NNZ40.
Medication
Class
Agent
Study Name/
Phase
Key Findings
Progestin Dienogest
DIVA
Observational study8
• ≈50% experienced strong improvement in QOL at 6 mo
• Over 75 mo, cumulative incidence of symptom recurrence was <10% with
dienogest compared to ≈80% without postoperative medication
Aromatase
inhibitor
Anastrazole Phase 2b study2
• Ongoing randomized, double-blind, double-dummy, parallel-group,
multicenter study in women with symptomatic endometriosis
• Anastrozole and levonorgestrel in an intravaginal ring vs placebo and
leuprorelin/leuprolide acetate
• Anticipated N = 272
SPRM Vilaprisan
VILLENDO
Phase 2b9
• Ongoing randomized, double-blind, parallel-group, placebo-controlled
study assessing two different doses of vilaprisan for 24 wk in women
with symptomatic endometriosis
• Primary endpoint: 7-day mean “worst pain” from baseline to mo 3
• Anticipated N = 315
Agents in Endometriosis-Associated Pain (Cont’d)

6. Treatment Options for Endometriosis-Associated
Pain and Uterine Fibroids—Insights From SEUD 2019
PRACTICE AID
Access the activity, “Advances in Medical Options for Uterine Fibroids and Endometriosis:
Clinical Highlights From Montreal,” at PeerView.com/NNZ40.
Medication
Class
Agent
Study Name/
Phase
Key Findings
GnRH
antagonist
Elagolix
ELARIS UF-1 and
ELARIS UF-2
Phase 310
• HMB was dramatically improved with elagolix compared to placebo in ELARIS UF-1
(84.1% vs 8.7%) and ELARIS UF-2 (76.9% vs 10.5%)
• Symptom severity and HRQOL were much improved with elagolix as well
ELARIS UF-EXTEND
Phase 311
• At 12 mo, elagolix 300 mg BID + add-back reduced HMB (87.9% response)
• BMD loss was lower with elagolix + add-back therapy than elagolix alone
Linzagolix
PRIMROSE 1 and
PRIMROSE 2
Phase 312,13
• Ongoing randomized, placebo-controlled trials assessing linzagolix alone and in
combination with add-back therapy for the reduction of HMB associated with UF in
premenopausal women
• Primary endpoint: Percentage of responders based on MBL volume reduction at wk 24.
Secondary endpoints include amenorrhea, time to amenorrhea, time to reduced MBL,
and number of days of uterine bleeding for each 28-day interval
• Anticipated N ≈ 500
Relugolix
Phase 2 study10
• Relugolix was associated with dose-dependent reductions in MBL; PBAC score <10 from
wk 6-12 was noted in 83.6% of patients receiving relugolix 40 mg/d, 43.6% of patients
receiving 20 mg/d, and 20.8% of patients receiving 10 mg/d compared to 0 patients
receiving placebo
• Dose-dependent improvement was noted in all secondary endpoints as well (proportion
of patients with amenorrhea and changes in myoma volume and uterine volume)
• Once-daily oral relugolix was noninferior to monthly leuprorelin injection
LIBERTY 1
Phase 310
• Significant response in relugolix combination arm (73.4%) compared to placebo
(18.9%; P <.0001)
• Reduction in MBL vs baseline with relugolix combination treatment was 84.3% (P <.0001)
• Relugolix also reduced pain, improved QOL, achieved amenorrhea, improved anemia,
and reduced uterine volume in significantly higher proportion of patients
Agents in Uterine Fibroids

7. Treatment Options for Endometriosis-Associated
Pain and Uterine Fibroids—Insights From SEUD 2019
BID: twice daily; BMD: bone mineral density; GnRH: gonadotropin-releasing hormone; HMB: heavy menstrual bleeding; IL: interleukin; MBL: menstrual blood loss; PBAC: pictorial blood loss assessment chart; QD: daily; SEUD: Society for Endometriosis and Uterine Disorders; SPRM:
selective progesterone receptor modulator; UF: uterine fibroids; UFS-QOL: Uterine Fibroid Symptom and Quality of Life; UPA: ulipristal acetate.
1. Zhang X et al. Multicentre, Prospective, Non-Interventional Study of the Efficacy of 24 Weeks of Treatment With Triptorelin Following Conservative Surgery in Deep Infiltrating Endometriosis: A 24-month Analysis. Society of Endometriosis and Uterine Disorders Congress
2019 (SEUD 2019). 2. Petraglia F. Plenary on Endometriosis: From Bench to Bedside. SEUD 2019. 3. Taylor HS et al. N Engl J Med. 2017;377:28-40. 4. Taylor H et al. Linzagolix for Endometriosis-Associated Pain (EAP): Primary Efficacy and Safety in a Dose-Ranging Trial. SEUD 2019. 5.
https://clinicaltrials.gov/ct2/show/NCT03204318. Accessed June 12, 2019. 6. https://clinicaltrials.gov/ct2/show/NCT03204331. Accessed June 12, 2019. 7. https://clinicaltrials.gov/ct2/show/NCT03654274. Accessed June 12, 2019. 8. Singh S, Murji A. New Insights From Endometriosis
Management in the Real World: Learnings From a Large Observational Study. SEUD 2019. 9. https://clinicaltrials.gov/ct2/show/NCT03573336. Accessed June 12, 2019. 10. Al-Hendy A. Novel Natural and Synthetics Compounds for Treatment of Uterine Fibroids: From Bench to
Bedside. SEUD 2019. 11. Lamb YN. Drugs. 2018;78:1501-1508. 12. https://clinicaltrials.gov/ct2/show/NCT03070899. Accessed June 12, 2019. 13. https://clinicaltrials.gov/ct2/show/NCT03070951. Accessed June 12, 2019. 14. Gemzell-Danielsson K. Efficacy and Safety of the Selective
Progesterone Receptor Modulator Vilaprisan: Integrated Analysis of Phase 2 ASTEROID 1 and 2 Studies. SEUD 2019. 15. https://clinicaltrials.gov/ct2/show/NCT03400826. Accessed June 12, 2019.
PRACTICE AID
Access the activity, “Advances in Medical Options for Uterine Fibroids and Endometriosis:
Clinical Highlights From Montreal,” at PeerView.com/NNZ40.
Medication
Class
Agent
Study Name/
Phase
Key Findings
SPRM
Ulipristal acetate
VENUS II
Phase 310
• Rate of amenorrhea (42% with UPA 5 mg and 54.6% with UPA 10 mg vs 0 with
placebo) and UFS-QOL (48.3% with UPA 5 mg and 56.7% with UPA 10 mg vs
13% with placebo) were substantially improved in a dose-dependent manner
• No evidence of liver injury was noted in this trial
• However, due to concerns with liver toxicity in other studies, UPA is not
approved for use in the US
Vilaprisan
ASTEROID 1 and
ASTEROID 2
Phase 214
• Best 12-wk outcomes were noted with vilaprisan 2 mg compared to UPA 5 mg
or placebo
• Vilaprisan rapidly controlled HMB in >96% of patients, induced reversible
amenorrhea in >83% of patients, decreased mean UF volume by 29%,
and increased symptomatic relief in 63% of patients (“much better” or “very
much better”)
Statin Simvastatin Phase 2 study15
• Ongoing double-blind randomized placebo-controlled trial assessing
simvastatin 40 mg/d for 12 wk followed by surgery
• Primary endpoint: Change in tumor size. Secondary endpoints include clinical
symptom improvement and adherence to the recommended treatment dosing
• Anticipated N = 60
Agents in Uterine Fibroids (Cont’d)