Advances in the management of Abnormal Uterine Bleeding

Dr. Sikolia WanyonyiResident II

Dr. Timona OburaSenior Instructor & Program Director

AKUH-EA

..If a woman… bears a male child, she shall be …unclean seven days; as at the time of her menstruation, she shall be unclean. Her time of blood purification shall be thirty-three days…she bears a female child, she shall be unclean two weeks..; her time of blood purification shall be sixty-six days.(Lev. 12:2-5)

‘..And a woman was there who had been subject to bleeding for twelve years, but no one could heal her. She came up behind him and touched the edge of his cloak, and immediately her bleeding stopped..’ Luke 8:43-44

Ayurveda, 5000 B.C. describe the amount of normal blood flow during menses as four ‘Anjalis’. An anjali is the volume of fluid that can be accumulated in the hollow when one joins the two hands.

Epidemiology

12 month accumulative incidence Menorrhagia 25% Metrorrhagia 29% Oligomeonorrhea 15% Intermenstrual bleeding 17% Postcoital bleeding 6%

Shapley et al Br. J Gen Pract: 2004; 54:359

Walraven et al. Menstrual disorders in rural Gambia, Stu Fam Plan 2002; 33(3) 261-8

AUB: commonest indication for hysterectomies (46%)

VALUE study. BJOG 2004; 11, 688-694

Normal menstrual bleeding

Endocrine signals ensure Regular Predictable Consistency

Ovarian and Endometrial cycles

Menstrual flow Characteristics*

Normal Abnormal

Duration 4-6 days Less than 2 or more than 7 days

Volume 30mL More than 80 ml

Interval 24-35 days

*Hallberg et al,1966; Cole et al, 1971;

Estimation of menstrual loss

Presence of clots Use of more than one tampoon/pad Pictorial blood loss assessment

Accurate assessment Collect all pads Determine the Hb changes

Onset and cessation menses

Initiation Classic hypoxia theory

Ischemic necrosis of endometrial vasculature

Enzymatic theory autodigestion of the functional layer of

the endometrium

Progesterone withdrawal

Release of intracellular lysosomal enzymes

Stimulates inflammatory response in endometrium

Stimulates matrix metalloproteinases

Cessation Coagulation mechanisms Local vasoconstriction Release of growth factors Increasing estradiol

Anovulatory bleeding

Increased density of abnormal vessels with fragile structure

Focal rupture release of lysosomal proteolytic enzymes

from surrounding epithelial and stromal cells

migratory leucocytes and macrophages

Abnormalities of menstruation

Oligomenorrhea: Intervals >35 days Polymenorrhea: Intervals < 24 days Menorrhagia: Regular normal intervals,

excessive flow or duration Metrorrhagia: Irregular intervals,

excessive flow or duration

Diagnostic Evaluation

Careful menstrual history Laboratory tests; not always useful Aspiration biopsy Uterine imaging Sonohysterography Hysteroscopy

TREATMENT MODALITIES

Goals of treatment

Treat underlying cause Correct associated problems (anemia) Prevent recurrences

Take into consideration the patients’ contraceptive needs and fertility

Treatment

Induce or restore cyclic predictable menses of normal volume and duration

Treatment

The key to successful clinical management is to recognize or identify which mechanism is operating or responsible

Traditional treatment modalities

Progestin therapy

Powerful anti-estrogens Stimulate 17β- hyrodroxysteroid

dehydrogenase and sulfotransferase activity

Inhibit estrogen’s induction of its own receptors

Suppress estrogen mediated transcription of oncogenes

Progestin therapy

Antimitotic, growth limiting effects of progesterone and progestins on endometrium Prevents and reverses hyperplasia Arrest growth during the secretory phase

of the cycle

Progestin therapy

Cyclical treatment with progesterone Works well in women who are

anovulatory Do not suppress HPO axis or ovulation

Combined Oral contraceptive therapy

Prolonged episodes of heavy anovulatory bleeding

Use low dose monophasic combination pills

Treatment should continue for at least 5-7 days even after bleeding stops

Combined Oral contraceptive therapy

Pretreatment TVS To confirm the diagnostic impression To minimize the risk of unsuccessful

treatment with continued heavy blood loss

Combined Oral contraceptive therapy

DMPA in contraceptive doses can be used in women with difficulty in taking COCPs

NSAIDS

PGE2 and PGF2α increase in endometrium during the menstrual cycle

NSAIDS inhibit PG synthesis and decrease menstrual blood loss

Alter balance of TXA2 and PGI2

Decrease menstrual blood loss by 20-40%

Antifibrinolytics

Tranexamic acid Reversibly blocks lysine binding sites on

plasminogen Prevents fibrin degradation More effective than NSAIDS and

progestins Reduce flow by up to 55%

Estrogen therapy

Best used when a denuded or attenuated endometrium is suspected Low yield of biopsy tissue Chronic progestin treatment Thin endometrial stripe

Dilation and curettage

Denudation of the basal layer Stimulates the normal processes

involved in cessation of normal menstrual bleeding

Can be used in acute presentation

NOVEL TECHNIQUES

The LNG-IUS-Mirena®

Has a reservoir containing 52 mg LNG mixed with polydimethylsiloxane

Used as a contraceptive Licensed for AUB in some countries Releases 20µg of levonogestrel per

day

The LNG-IUD-Mirena®

Rapidly absorbed from uterine cavity Plasma concentrations plateaus at 1

month( 0.4-0.6 nmol/L) Intrauterine concentrations of LNG are

1000 times higher in IUS compared to subdermal implants

The LNG-IUD-Mirena

Mode of action

LNG is highly progestational Suppression and atrophy of the

endometrium Stroma swell, decidua, mucosa and

epithelium become inactive Decrease in mean vascular density

Endometrial ablation

Twenty (20) years old Minimally invasive technique Used for unexplained menorrhagia

when medical treatment are rejected, unsuccessful, or poorly tolerated

Could be hysteroscopic or non-hysteroscopic

Mode of action

Endometrial destruction Use of energy to produce necrosis of

full thickness of endometrium 1st generation: heat, laser 2nd generation:heat,cold, microwave,

suction

Criteria for endometrial ablation

Abnormal uterine bleeding No desire for amenorrhea Unsuccessful medical treatment Endometrial biopsy negative for atypia

and cancer Family complete

Exclusion criteria

Coexisting gynecological pathology Endometria atypia and cancer Submucous fibroids> 5cm Uterus more than 12 weeks in size Anovulation, endometrial hyperplasia

First generation

Roller ball ablation Loop endometrial section Laser ablation

First generation

Used in operating theatre under GA A non-ionic, low viscosity fluid (1.5%

glycine) used for uterine distention Fluid overload is possible

Long term risks

Post ablation pregnancy Hematometra from cervical stenosis Uterine synechiae Occult endometrial carcinoma

2 direct deaths reported in the MISTLETOE study* (10,686 women)

*Overton et al BJOG 19997;104:1351

First generation

Neither of the methods can guarantee sterility

Risk of uterine perforation is greatest at the uterine cornu as the myometriun is thinnest

Hormonal preparation not necessary prior to loop resection

Use of bipolar for endometrial resection improves safety

First generation

Take biopsy prior to roller ball or laser Success and safety is dependent on

the experience of the surgeon

Second generation

Cryotherapy Fluid balloon Microwave ablation Electrode Hydrothermoblation Laser interstitial hyperthermy Photodynamic therapy

Second generation

Different devices vary in their ability to treat non standard uteri

2nd generation devices show no difference in the short term outcomes, patient satisfaction (MISTLETOE study)

Lacking RCTs on the cost effectiveness of this methods and safety

Overton et al BJOG 19997;104:1351

Role of GnRH agonists

Can achieve short-term relief from a bleeding problem

Preoperatively adjunct in women awaiting surgery

Prior to endometrial ablation

Doctor which is the best method for me?

‘....make the operation/treatment suit the patient, rather than the patient suit the operation…’ Dr. Charles Mayo

LNG-IUS or Hysterectomy

Clinical outcomes and costs: Randomised trial 5-year

follow-up

JAMA 2004; 291(12): 1456-63

JAMA. 2004; 291:1456-1463

Hurkainen R. JAMA. 2004;294:1456

Conclusion

LNG-IUS Provides improvement in health related

quality of life at a relatively low cost May decrease costs due to interventions

involving surgery

LNG or hysterectomy

Fall in Gyne surgery with the rise in use of IUS in Newcastle upon Tyne

LNG-IUS vs Endometrial ablation

Lower PBAC with ablation No difference in amenorrhea Comparable rates of satisfaction No difference in the requirement for

further surgery

Conhrane review 2007, issue 4. CD001501

The Medicine or Surgery (Ms) trial

Effect of hysterectomy on Health-Related Quality of Life and Sexual Functioning

JAMA. 2004; 291: 1447-1455

Copyright restrictions may apply.

Kuppermann, M. et al. JAMA 2004;291:1447-1455.

MCS and PCS scores Over Time

Copyright restrictions may apply.

Kuppermann, M. et al. JAMA 2004;291:1447-1455.

MCS and PCS Over Time

Conclusions

Hysterectomy improved HRQL after 6 months

Half of the women on medical treatment eventually opt for surgery later

HRQL is similar despite these between the two groups.

Endometrial ablation vs Hysterectomy

Hysterectomy Reduced HMB High satisfaction Improvement in

general health Higher costs

Ablation Less duration of

surgery Quicker recovery Less complications Higher rates of

repeat surgery

Conhrane review 2007, issue 4. CD000329

Complications of hysterectomy

The Vaginal Abdominal or Laparoscopic Uterine Excision

(VALUE) Study

BJOG 2004; Vol 111: 688-694.

Interaction of risk of severe complications between indication and age

Interaction of risk of severe complications by method and age

Conclusions

Severe complications are more common in younger women.

Less invasive options should be considered

They could effectively replace hysterectomy

“…Daughter, your faith has healed you. Go in peace…"

Thank you