the landscape of uterine fibroids · bulk symptoms… the best treatment option for you is a...

The Landscape of Uterine Fibroids: What Do We Know? What Do We Need? What Do Our Patients Need?

Erica E. Marsh, MD, MSCI, FACOGAssociate Professor and ChiefDivision of Reproductive Endocrinology and InfertilityDepartment of Obstetrics and GynecologyUniversity of Michigan Health SystemUniversity of MichiganAnn Arbor, Michigan

2

Fibroid

Fibroid

Fibroid

Fibroid

Fallopian tube

Ovary

Vagina

Cervix

Uterus

Presentation Overview

• Well circumscribed benign masses

• Single or multiple masses

• Whirled, shiny, white, bulging, rubbery cut surface

• Vary in size up to 100 lb

• Composed of irregular bundles of cells in an extensive connective tissue matrix

• Account for up to $34B annually

Leiomyoma leio (smooth) + myo (muscle) + oma (tumor)

Cardozo ER et al. Am J Obstet Gynecol. 2012;206(3):211.e1-e9.

3

Epidemiology

• Cumulative Incidence of 65% to 70%

• Risk Factors:– Race in AAW

– Obesity

– Hypertension

– Pelvic infections

– Alcohol in women who drink >7 beers/week

– Parity and smoking

Who gets uterine fibroids?

4

Altered Gene Transcription – sex steroids, RA, DNA methylation status, Vit D3Altered Gene Translation - miRNA

Endocrine, Paracrine, Autocrine and Growth Factors – Estrogen, Progesterone, TGF, Leptin, CCN5

Germ Line + Somatic Genetic Alterations –MED12, HLRCC/FH, TSC2, BHD, HMG

Epigenetics/DNA MethylationStem Cells

Altered Gene Transcription – sex steroids, RA, Vit D3, solid state signaling, dermatopontinAltered Gene Translation - miRNA

Altered Protein Processing

Pathophysiology of Fibroids

5Graphic courtesy of Dr E. Marsh

Disease Pathophysiology

6

Patient Centeredness

Health care that establishes a partnership among practitioners, patients, and their families (when appropriate) to ensure that decisions respect patients' wants, needs, and preferences and that patients have the education and support they need to make decisions and participate in their own care.

Crossing the Quality ChasmInstitute of Medicine, 2001

Institute of Medicine. Crossing the Quality Chasm. Washington, DC: National Academies Press; 2001.

7

“The right care, in the right way, at the right time”


8


"Nothing about me without me"

9

Institute of Medicine

• Core need for health care to be:

– Safe– Effective– Patient centered– Timely– Efficient– Equitable

Institute of Medicine. Crossing the Quality Chasm. Washington, DC: National Academies Press; 2001.

10

Reprinted with permission from the National Academies Press, Copyright 2001, National Academy of Sciences.

Provider Perspective

43-year-old G4P3 with 24-week–sized fibroid uterus, childbearing complete, HMB and bulk symptoms…

The best treatment option for you is a hysterectomy.

11

HMB=heavy menstrual bleeding.

Patient Perspective

“They viewed my uterus like it was a useless organ… They said, ‘Well, why do you want to keep it?’ …and I said, because it’s mine.”

12

Provider Perspective

13

Courtesy of Dr E. Marsh

Patient Perspective

14

Consequences

15

Adapted from Ghant MS et al. J Psychosom Res. 2015;78(5):499-503.

16

Beyond the Physical: A Qualitative Assessment of the Burden of Symptomatic Uterine Fibroids on Women’s Emotional and Psychosocial Health

Consequences

Ghant MS et al. J Womens Health (Larchmt). 2016;25(8):846-852.

17

An Altered Perception of Normal: Understanding Causes for Treatment Delay

in Women With Symptomatic Uterine Fibroids

Altered State of Normal

“…my period lasted for 30 days and it was heavy and it was horrible. I was wearing pads like the size that you get in the hospital after you have a baby, and I was so used to that happening, that at that time I didn’t call anybody because you know it was, like, ‘This is normal’.”

18

Limited Knowledge

“No, I had not. With a bachelor’s degree and a master’s degree in science and chemistry, I had not. Thinking back to anatomy and physiology classes, we talked about having babies, talked about different forms of cancer, but did they ever mention a fibroid?

“I don’t think so.”

19

Avoidance-based Coping Strategies

“…this is what you go through as a woman, and it was like every month you are going to bleed half to death and then the rest of the time you are almost okay. I just went with that… you know, it didn’t kill me, so I would just be stronger.”

20

Patient-Provider Interactions

• Pressure to obtain a hysterectomy

• Lack of discussion of treatment options

• Belittling of symptoms

• Treatment discouragement

21

Eight Dimensions of Patient-Centered Care

Adapted from Registered Nurses’ Association of Ontario. Best Practice Guidelines. Copyright 2015 by National Research Corporation Canada. Picker Institute. Principles of Patient-Centered Care. http://pickerinstitute.org/about/picker-principles/. Accessed July 24, 2017.

The Patient

22

Patient Perspectives

• Treatment Expectations

• Treatment Barriers

• Treatment Recovery and Satisfaction

• Financial Challenges

Sengoba KS et al. J Racial Ethn Health Disparities. 2017;4(2):178-183.

23

Racial/Ethnic Differences in Women’s Experiences With Symptomatic Uterine Fibroids: A Qualitative Assessment

Marsh EE et al. Int J Gynaecol Obstet. 2014;125(1):56-59.

24

Prevalence and Knowledge of Heavy Menstrual Bleeding Among African American Women

Type of ExperienceNo. of

Participants

Clinician seen for HMB 75

Treated for HMB 61

Hospitalized for HMB 35

Presented to emergency department for HMB

34

Type of Treatment% of

Participants

Oral Contraceptives 24.6

Hysterectomy 19.7

Endometrial Ablation 4.9

Depo-Lupron 4.9

Depo-Provera 1.6

Myomectomy 1.6

Other 1.6

Summary• Patient centeredness is 1 of 6 aims identified by the IOM to

address in order to elevate the quality of patient care in the United States

• Fibroids cause emotional and psychological trauma for many patients

• Despite being significantly symptomatic, women are delaying their fibroid treatment

• Many patients report negative provider interactions during their fibroid evaluation—even if they are ultimately comfortable with their care

• Approximately 50% of women in our study reported negative feelings about hysterectomy as a treatment choice

• 28% of women reported being discouraged to pursue any treatment

25

Conclusions• Better and more tailored education is needed for women

regarding fibroid symptoms, diagnosis, and treatment options

• Many women are looking for low risk/no risk treatment options and would rather continue to be severely symptomatic than accept the available treatment options

• There is a disconnect between providers and patients during fibroid counseling and, thus, an opportunity and need to optimize patient-centered care by increasing provider sensitivity and awareness of women’s values, fears, and concerns during their evaluation and by developing research aimed at understanding the health-seeking behaviors and needs of women with fibroids

26

Expanding Medical Treatment Options for Uterine Fibroids

Sukhbir Sony Singh, MD, FRCSC, FACOG (Program Chair)

Associate Professor and Vice‐Chair of Gynecology

Department of Obstetrics and Gynecology

The Ottawa Hospital

University of Ottawa

Ottawa, Ontario, Canada

27

IMPACT OF UTERINE FIBROIDS

28

29

Uterine Fibroids Are TOUGH

• Common and growing problem

• Demand for uterine sparing and fertility preservation procedures increasing

29

Courtesy of Dr S. Singh

Uterine Fibroids Are Common

• Estimated cumulative incidence by age 50– >80% for black women– Almost 70% for white women

• Estimated prevalence of clinically relevant fibroids– 50% of premenopausal black women– 25% of premenopausal white women

Baird DD et al. Am J Obstet Gynecol. 2003;188(1):100-107. 30

Impact of Fibroids

• One of the main reasons for hysterectomy

• By late 40s– 80% of African American– 70% of White

31


Uterine Fibroids are TOUGH

• Surgical risks are REAL

• Skilled and willing surgeons are decreasing

32


S. Singh

33

Adhesions after myomectomy

Adhesions after myomectomy


Fibroids…

34


Fibroids…

35


Fibroids…

36


Fibroids…

37


Fibroids…

38


Fibroids…

39


Fibroids…

40


Fibroids…

41


Uterine Fibroids Are TOUGH

• Pathology Scares Us!

Smooth Muscle Tumor of Uncertain Malignant Potential

42



WHAT IS THE IDEAL THERAPY?

43

The Perfect Treatment Should….

• Manage signs and symptoms

• Offer sustained reduction in size of fibroids

• Preserve fertility

Miller CE. J Minim Invasive Gynecol. 2009;16(1):11-21. 44

Mass effectsrelated to the

size and locationof fibroids

Reproductivedysfunction

Bleedingcomplaints

These have been shown to diminish quality of life

Range of Symptoms Associated With Uterine Fibroids*

Tropeano G et al. Hum Reprod Update. 2008;14(3):259-274; Downes E et al. Eur J Obstet Gynecol Reprod Biol. 2010;152(1):96-102; Viswanathan M et al. Evid Rep Technol Assess (Full Rep). 2007;154:1-122.

*Not all fibroids are symptomatic

Nearly half of women with fibroids have significant and often disabling symptoms

Symptomatic fibroids*

45


Management Options for Fibroids

Fibroid

Fibroid

Fibroid

Fibroid

Fallopian tube

Ovary

Vagina

Cervix

Uterus

UTERUS WITH FIBRO I DS

Fibroid

Fibroid

Fibroid

Fibroid

Fallopian tube

Ovary

Vagina

Cervix

Uterus

UTERUS WITH FIBRO I DS

46


Evaluation

• Evaluate abnormal uterine bleeding

• Imaging to localize fibroids– Transvaginal ultrasound

– Saline infusion hysterography

– MRI

– Hysteroscopy

47

Fibroid

Fibroid

Fibroid

Fibroid

Fallopian tube

Ovary

Vagina

Cervix

Uterus

UTERUS W ITH FIBRO IDS

Fibroid

Fibroid

Fibroid

Fibroid

Fallopian tube

Ovary

Vagina

Cervix

Uterus

UTERUS W ITH FIBRO IDS


PALM‐COEIN Classification of AUB

Leiomyoma Subclassification System

S M – Submucosal 0 Pedunculated Intracavitary

1 <50% Intramural

2 ≥ 50% Intramural

O – Other 3 Contacts endometrium; 100% Intramural

4 Intramural

5 Subserosal ≥50% Intramural

6 Subserosal < 50% Intramural

7 Subserosal Pedunculated

8 Other (specify, eg, cervical, parasitic)

00

22

33

11

44

5566

77

00

2-52-5

0

2

3

1

4

56

7

0

2-5

Polyp

Adenomyosis

Leiomyoma

Malignancy & Hyperplasia

Coagulopathy

Ovulatory Dysfunction

Endometrial

Iatrogenic

Not Yet Classified

Submucosal

Other

Munro MG et al; FIGO Working Group on Menstrual Disorders. Int J Gynaecol Obstet. 2011;113(1):3-13.

AUB=Acute uterine bleeding.

PALM = Visually objective structural criteria

COEI = unrelated to structural anomalies N = entities not yet classified

48Copyright © 2011, Elsevier Ireland Ltd. Reprinted with permission.

The Current State in the United States vs World 2017

USA Current Worldwide

SurgeryMyomectomy and Hysterectomy

InterventionalUterine Artery EmbolizationMRI Focused UltrasoundRadiofrequency Ablation

Medical Management of SymptomsBleeding – Hormonal Suppression and Tranexamic Acid

Pressure – GnRH agonist

X Long‐Term Medical Long‐Term MedicalSelective Progesterone Receptor Modulators

49GnRH=gonadotropin-releasing hormone.

Uterine Fibroid Treatment Algorithm

Singh SS, Belland L. Contemporary management of uterine fibroids: focus on emerging medical treatments. Current Medical Research and Opinion. 2015;31(1):1-12. Reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com.

AsymptomaticAsymptomatic

Uterinefibroids

Symptomatic

Fertility notFertility notdesired

Fertilitydesired

Desire to preserveDesire to preserveuteruspreserve uterus

No desire topreserve uterus

Watchfulwaiting

HysterectomyHysterectomyPresurgicalmedical txPresurgicalmedical tx

Long termmedical txLong‐termmedical tx

Myomectomy

Uterine arteryembolizationUterine arteryembolization

Myolysis

EndometrialEndometrialablation

Presurgicalmedical tx


MyomectomyMyomectomy


Presurgicalmedical txPresurgicalmedical tx

Medical treatment includes:1. Fibroid‐directed therapies:

ulipristal acetate and GnRH agonists

2. Symptom‐relieving therapies (eg, OCs, Levonorgestrel IUS,danazol)IUS=Intrauterine system.

50

Symptomatic Fibroids

OPTIONS

Medical

Symptom Management

Targeted Therapy

Interventional Surgery

Myomectomy Hysterectomy

51


Medical

Symptoms

TranexamicAcid

Hormonal Contraception

Targeted Therapy

SPRMsGnRH

Analogues

SPRMs=selective progesterone receptor modulators.


52


Targeted Therapy

SPRMsGnRH

Analogues


53


GnRH Agonists

• 35%–65% uterine/fibroid size

• 3–6 months preoperatively + Fe– Facilitates MIS surgery– Optimizes Hb prior to surgery

• Disadvantages: flare, vasomotor sx, bone loss (6%/ 12mo), grow back

Singh SS, Belland L. Curr Med Res Opin. 2015;31(1):1‐12. 54

GnRH Antagonists

• Novel oral agents that may mimic efficacy of GnRH agonist, but allow for dosing variation

• Elagolix is currently being studied

• Balancing side effect of hypoestrogenism is main challenge

ClinicalTrials.gov. Safety and Efficacy Pre-Menopausal Women With Heavy Uterine Bleeding and Uterine Fibroids. NCT01441635. https://clinicaltrials.gov/ct2/results?term=NCT01441635&Search=Search. Accessed April 28, 2017. 55


Long‐Term Targeted Therapy

SPRMs

56Courtesy of Dr S. Singh

SELECTIVE PROGESTERONE RECEPTOR MODULATORS (SPRMs)*

57*Not currently FDA approved for the treatment of uterine fibroids

Progesterone

Factors Controlling Fibroid Growth

From Walker CL, Stewart EA. Uterine fibroids: the elephant in the room. Science. 2005;308(5728):1589-1592.58

Reprinted with permission from American Association for the Advancement of Science.

Selective Progesterone Receptor Modulators

• First PR antagonist, mifepristone (RU 486), discovered in 1980

• Other PR ligands developed with mixed activity:

– Agonistic and/or antagonistic depending on the tissue (SPRMs):

Bouchard P et al. Fertil Steril. 2011;96(5):1175-1189; Spitz IM. Curr Opin Investig Drugs. 2006;7(10):882-890.

Antagonists AgonistsMesoprogestins

OnapristoneMifepristone

Ulipristal acetateAsoprisnil

Telapristone acetateJ 1042

ProgesteroneR5020 (synthetic

progestin)

59


The SPRM Class

• Bind to progesterone receptors

• Modulate transcription in a positive or negative manner in tissue‐specific ways

• Have short‐term effects on endometrial proliferation

• Inhibit proliferation and induce apoptosis in cultured leiomyoma cells, but not normal myometrial cells

Bouchard P et al. Fertil Steril. 2011;96(5):1175-1189. 60

Vilaprisan Is a Potent Selective Progesterone Receptor Modulator

• Vilaprisan demonstrated a favorable, selective receptor‐binding profile

• Phase 1 and Phase 2 studies have confirmed the results from preclinical models

61

Wagenfeld A et al. Hum Reprod. 2013;28(8):2253-2264; Schütt B et al. Hum Reprod. 2016;31(8):1703-1712; Bradley L et al. Presented at: American Society for Reproductive Medicine Annual Meeting; October 16-20, 2016; Salt Lake City, UT. O-235.

SPRMs*THE KEY POINTS

*AVAILABLE SINCE JULY 2013 IN CANADA

62

Direct action on fibroids, reducing their size through the inhibition of cell proliferation and induction of apoptosis

Direct effect on the endometrium• Stops uterine bleeding• Results in benign and reversible changes in endometrial tissue, “Progesterone Receptor Modulator‐Associated Endometrial Changes” (PAEC)

Direct action on the pituitary, inducing amenorrhea by inhibiting ovulation and maintaining mid‐follicular phase levels of estradiol

Horak P et al. Int J Endocrinol. 2012;2012:436174; Donnez J et al; PEARL I Study Group. N Engl J Med.2012;366(5):409-420; Donnez J et al; PEARL II Study Group. N Engl J Med. 2012;366(5):421-432; Fibristal Product Monograph. Mississauga, Ontario, Canada: Actavis Specialty Pharmaceuticals Co. June 2013

PituitaryEndometriumFibroids

SPRM Mechanism of Action

63

Courtesy of Dr S. SinghCourtesy of Dr S. Singh

Ulipristal Acetate Clinical Trials: Randomized, Phase III

2008 2009 2010 2011 2012 2013 2014

June2012

Dec2014

451 patients in 11 countries

PEARL IV

Double‐blind

Jan2013

Jul2010


PEARL III (and extension)

Open‐label

Aug2008

Jun2010

301 patients in 9 countriesPEARL II

• Parallel‐group•Double‐blind•Double‐dummy•Active‐comparator–controlled

Oct2008

Aug2010

• Parallel‐group•Double‐blind• Placebo‐controlled


PEARL I

Donnez J et al; PEARL I Study Group. N Engl J Med. 2012;366(5):409-420; Donnez J et al; PEARL II Study Group. N Engl J Med. 2012;366(5):421-432; Donnez J et al; PEARL III and PEARL III Extension Study Group. Fertil Steril. 2014;101(6):1565-1573.e1-e18; Donnez et al. Fertil Steril. 2016;105(1):165-173.e4.

64

All Trials Conducted in Europe


65

Ulipristal Acetate: Canadian Intermittent Dosing Schedule

Fibristal (ulipristal acetate) Canada Product Monograph, Allergan Inc. November 7, 2016.

Repeated intermittent treatment has been studied up to 4 intermittent courses.

Menses

UPA

5 mg 5 mg 5 mg 5 mg 5 mg

3 months on

3 months on

3 months on

3 months on

2 months off

2 months off

2 months off

2 months off

FIBRISTAL® (ulipristal acetate) is indicated for:• Treatment of moderate to severe signs and symptoms of uterine fibroids in adult women of reproductive age, who are

eligible for surgery• Intermittent treatment of moderate to severe signs and symptoms of uterine fibroids in adult women of reproductive ageThe duration of each treatment course is 3 months.

First treatment course begins during first week of menstruation

Treatment‐free intervals for one full menstrual cycle

Re‐treatment courses begin, at the earliest, during first week of second menstruation following previous treatment course

UPA=ulipristal acetate.


Time to Control of Bleeding in Patients With PBAC <75

0

20

40

60

80

100

0 10 20 30 40 50 60 70 80 90 100

Time (days)

Patients (%)

7 days

Bleeding was controlled 7 days from treatment initiation in 75.9% of UPA 5 mg patients and in 82.7% of UPA 10 mg patients

Donnez J et al; PEARL I Study Group. N Engl J Med. 2012;366(5):409-420.

76% at 8 days92% EOT

EOT=end of treatment; PBAC=pictorial blood-loss assessment chart.66Courtesy of Dr S. Singh

UPA 10 mg PlaceboUPA 5 mg

Censored observations (ie, a patient had < 8 days at the end of the treatment period for which the total PBAC score met the criterion).

Time to Control of Bleeding (PBAC <75)

Donnez J et al; PEARL II Study Group. N Engl J Med. 2012;366(5):421-432.

0

20

40

60

80

100

0 10 20 30 40 50 60 70 80 90 100

Time (days)

Patients (%)

7 days 30 days

UPA 10 mg (n = 95) Leuprolide 3.75 mg (n = 93)UPA 5 mg (n = 93)

Uterine bleeding was controlled in 90% of patients on UPA 5 mg, in 98% of those on UPA 10 mg, and in 89% of those on leuprolide acetate

EOT:5 mg: 90% 10 mg: 98% GnRHa: 89%

30 days

67Courtesy of Dr S. Singh

Censored observations (ie, a patient had < 8 days at the end of the treatment period for which the total PBAC score met the criterion).

UPA vs GnRH agonist: Fibroid Volume Reduction

Donnez J et al; PEARL I Study Group. N Engl J Med. 2012;366(5):409-420; Donnez J et al; PEARL II Study Group. N Engl J Med. 2012;366(5):421-432; Donnez J et al; PEARL III and PEARL III Extension Study Group. Fertil Steril. 2014;101(6):1565–1573.e1-e18; Donnez J et al. Fertil Steril. 2016;105(1):165–173.e4.

Median change from baseline in fibroid volume* after each treatment course

• *PEARL I: total fibroid volume; PEARL II, III, IV: combined volume of 3 largest fibroids; †10-mg UPA dose not licensed 68

‐75

‐50

‐25

0

Treatment Course 2

Treatment Course 3

Treatment Course 4

3‐monthFollow‐up

Treatment Course 1

n 130 119 106 96 97207 189 173 160 158

Med

ian change in

fibroid volume (%

)

UPAPEARL IV

UPA†PEARL III

GnRHa (n = 93)

UPA (n = 93)

PEARL II

Placebo (n = 48)

UPA (n = 95)

PEARL I


Ulipristal Acetate 5 mg Clinical Summary

• Rapidly stopped excessive bleeding: 75% normalized menstrual bleeding (7 days), 50% amenorrhea (10 days)

• After 3‐month course: 90%–92% controlled excessive menstrual bleeding, 73%–75% induced amenorrhea

• Significantly reduced volume of the 3 largest fibroids– Maintained for up to 6 months after treatment cessation

Compared to GnRH agonist, UPA:• Controlled bleeding faster• Maintained fibroid volume reduction for up to 6 months• Had a better side‐effect profile

Donnez J et al; PEARL II Study Group. N Engl J Med. 2012;366(5):421-432; Donnez J et al; PEARL I Study Group. N Engl J Med. 2012;366(5):409-420.

69

70

UPA Research in US Population

71

• Venus 1– Simon et al. American Society for Reproductive Medicine (ASRM) 2016

– Phase 3 randomized double‐blind study – UPA (2 doses) vs placebo – n=157, 69% African American

– UPA superior to placebo

Simon JA et al. Ulipristal acetate treatment of uterine fibroids in black and obese women: Venus I Subgroup Analyses [28G]. Obstet Gynecol. May 2017. Presented at: The American College of Obstetricians and Gynecologists; May 6-9, 2017; San Diego, CA.

Venus 1 – ACOG 2017

72

Simon JA et al. Ulipristal acetate treatment of uterine fibroids in black and obese women: Venus I Subgroup Analyses [28G]. Obstet Gynecol. May 2017. Presented at: The American College of Obstetricians and Gynecologists; May 6-9, 2017; San Diego, CA.

BMI=body mass index.© 2017 Allergan. All rights reserved. Used with Permission.

73

Sustainability of Fibroid Volumea Reduction in Subjects Who Did Not Undergo a Procedure

Donnez J et al; PEARL II Study Group. N Engl J Med. 2012;366(5):421-432.

aMeasured by ultrasoundbChange from end of treatment (week 13) to 6‐month follow‐up for UPA 5 mg and UPA 10 mg vs leuprolide p < .05

EOTFollow‐up

EOTFollow‐up

EOTFollow‐up

‐46

‐50

‐45b

‐56

‐17

‐43

‐62

‐57‐55b

3‐mo 6‐mo 3‐mo 6‐mo 3‐mo 6‐mo

LeuprolideUPA 5 mg UPA 10 mg

0

‐10

‐20

‐30

‐40

‐50

‐60

‐70n = 45 n = 46 n = 44

Courtesy of Dr S. SinghUAE=uterine artery embolization.

SPRM Safety Summary

• Safe overall with some nuisance side effects

• No evidence that it leads to endometrial hyperplasia or malignancy

• Progesterone receptor modulator‐associated change

74

Progesterone Receptor Modulator‐Associated ChangeBenign Condition and Completely Reversible

Singh SS, Belland L. Curr Med Res Opin. 2015;31(1):1‐12. 75


Limitations of SPRM Treatment

• Non‐responders– 20% of fibroid volume– <10% bleeding

• Intermittent use

• Effects on surgical planes?

• Reproductive effects long term

76

SPRMs: How are they being used?

• Preoperative optimization– Improve blood count before surgery by stopping bleeding

• Control symptoms in:– Those who don’t want surgery– Those who cannot have surgery– Those close to menopause

• Potentially LONG‐TERM intermittent therapy

77

The Future Possibilities

Medical Therapy

78


PostponeOr

Avoid Surgery

PrimaryPrevention*

SecondaryPrevention*

* Theoretical hypothesis, not based on clinical research

the landscape of uterine fibroids · bulk symptoms… the best treatment option for you is a...

Documents