Treatment Goals of AUB

 Control bleeding
 Prevent recurrence
 Correct anaemia
 Improve quality of life

Any interventions should aim to improve quality of life measures.

NICE guideline, 2007
 Management options of AUB

Medical Surgical
management management
When should we consider medical management ???

if there is : -

 No histological and major structural abnormality

 Fibroids <3cm in diameter causing no distortion
of uterine cavity

Medical management is the first line therapeutic option.

NICE guideline, 2007
 Medical treatment options

Non-hormonal treatment Hormonal treatment

Non-hormonal treatment
Non-steroidal anti-inflammatory drugs (NSAIDs)
Non-steroidal anti-inflammatory drugs (NSAIDs)

 Commonly used NSAIDs:- mefenamic acid, ibuprofen and

naproxen

 reduced menstrual blood loss by 33% to 55%

 The effect in reduction of menstrual blood loss is comparable

to COC and progestins.

 Less effective than tranexamic acid and LNG-IUS

 No individual variations among NSAIDs

Non-steroidal anti-inflammatory drugs (NSAIDs)

 additional benefit of improving dysmenorrhea for up to

70%

 Start at the first day of menses and continued for 5 days

or until cessation of menstruation

 If it does not improve symptoms within 3 menstrual

cycles, stop treatment.
Non-steroidal anti-inflammatory drugs (NSAIDs)

 Adverse effects : nausea, vomiting, abdominal pain,

headache

 contraindications : women with bleeding disorders or

platelet function abnormalities
 Antifibrinolytic agent (Tranexamic acid)

 Synthetic derivative of lysine

 Tranexamic acid is an anti-fibrinolytic drug that

reduces blood loss given only with menstruation in
women with heavy menstrual bleeding.
Antifibrinolytic agent (Tranexamic acid)
 Antifibrinolytic agent (Tranexamic acid)

 Recommonded dose : one gram orally every 6 hours for

the first four days of the cycle

 Intravenous tranexamic acid is available for more acute

scenarios, with a dose of 10 mg/kg every 6 hours.

 Reduce the menstrual blood loss by up to 40%

 does not treat dysmenorrhea

 Antifibrinolytic agent (Tranexamic acid)

 If tranexamic acid does not decrease menstrual blood loss

within 3 cycles, it should not be continued.

 Side effects are usually mild, but may include nausea,

vomiting, diarrhea, and headaches.

 The risk of venous thromboembolism by tranexamic acid is

controversial.

 Regardless of the lack of evidence, antifibrinolytics should

be used with caution in patients with risk factors for
thrombosis or when prescribed with CHCs.
 Antifibrinolytic agent (Tranexamic acid)

 Tranexamic acid and NSAIDs can be used together

but should be stopped after 3 months if there is no
symptomatic improvement.

 If they are beneficial, they may be continued

indefinitely.

 They can also be used as adjuvant therapy with

hormonal preparations.
Hormonal treatment
Combination hormonal contraceptives (CHCs)

Excellent choice for women with abnormal bleeding

who are seeking a reliable method of contraception

 progesterone component – suppress ovulation,

inhibits ovarian steroidogenesis and create endometrial
atrophy

 Estrogen component - supports to the endometrium to

reduce unscheduled breakthrough bleeding
Combination hormonal contraceptives (CHCs)

 excellent cycle control

 significantly reduce menstrual loss (up to 40% to 50%)

 improve dysmenorrhea
Combination hormonal contraceptives (CHCs)

Types of CHCs
 oral contraceptive pill
 contraceptive patch
 vaginal ring

All CHCs are effective in reduction

of menstrual blood loss.
Regiemes

 21 days, followed by 1 pill free week

reduce MBL up to 40-50%

 Continuous use of CHCs without the hormone-free

interval
induce amenorrhea in 80–100% of women by 10–12
months
The possible side effects Contraindications

 breast tenderness  women who are over 35 yrs old

 mood change who smoke
 headache  hypertension
 nausea  cardiovascular disease
 vomiting  migraine with aura
 breast cancer
 venous thromboembolism or
thrombogenic mutation
 Progestins

 Safer alternatives for women with fewer contraindications

compared to CHCs

 Oral progestin - norethindrone acetate (NETA)

medroxyprogesterone acetate (MPA)

 Injectable progestin - medroxyprogesterone acetate

(Depo-Provera)
 Progestins

Oral progestin

 Long-course (21 days per cycle) reduced

MBL in 63–78% of the women

 Short-course luteal phase progestin does

not produce significant benefit.

 Possible adverse effects : - unscheduled

bleeding, headache, breast tenderness,
nausea and vomiting
 Progestins

Injectable progestin

 induces amenorrhea by inhibition of FSH thus inhibiting

follicular development, reducing estradiol synthesis and
secretion resulting in a thin endometrium

 Administered every 12 weeks

 In trials, over half of the women became amenorrheic after 1

year, but many reported unscheduled bleeding in the first
few months.

 excellent contraception
 Progestins

Progestin
intrauterine system
(LNG-IUS)

 First line of treatment

in AUB (NICE, 2007)
Progestins (LNG-IUS)

Requires an endometrial cavity that is 6 to 9 cm

in length with minimal distortion
 Progestins (LNG-IUS)

 Approved for heavy menstrual bleeding treatment

for up to 5 years

 Minimal concentrations of LNG are absorbed into

the systemic circulation (0.4 to 0.6 nmol/L), limiting
the likelihood of systemic hormonal side effects.
 Progestins (LNG-IUS)

 amenorrheic by 12 months

 Changes in the bleeding pattern

lasting for longer than 6months,
particularly in first few cycles

 Should be advised to preserve for

at least 6 cycles to see the
benefits of the treatment

Andersson K, Odlind V, Rybo G. Levonorgestrel-releasing and copper-releasing

(Nova T) IUDs during five years of use: a randomized comparative trial.
Contraception 49(1), 56–72 (1994).
 Progestins (LNG-IUS)

Drawback:

 high cost

 spontaneous expulsion (7%)

 uterine perforation (1:1000 cases)

 Progestins (LNG-IUS)

 Common side effects

unscheduled bleeding, breast tenderness, abdominal/pelvic
pain/back pain, headache, ovarian cyst, and acne

 Contraindications
pregnancy, unexplained vaginal bleeding,
uterine sepsis
 Danazol

 Synthetic steroid with androgenic properties

 Anti-estrogenic and anti-progestogenic effect

 Can reduce the menstrual blood loss up to 80%

 Danazol

 100 to 400 mg/day in divided doses

 20% of women will become amenorrheic and 70%

reported oligomenorrhoea.

 The side effects:- androgenic effects such as hot

flushes, myalgia, weight gain and acne, which
occur in 85% of users.
 Danazol

 significantly more adverse effects than other medical

therapies

 should not be used routinely

 should be limited to 6 months

GnRH agonists
 GnRH agonists

Binds to GnRH receptor

Decreased FSH and LH
 GnRH agonists

 endometrial atrophy and amenorrhoea within 3–4 weeks

following initiation of treatment

 amenorrhea rate of up to 90%

 relief from dysmenorrhea associated with adenomyosis and

endometriosis

 increase the haematocrit level with minimal side effects

 GnRH agonists

 reduce uterine and leiomyoma volume by up to 60%

(reverses within months of stopping Rx)

 Use as short-term preoperative therapy

 adverse effects in long-term: bone pain, loss of bone density,

hot flashes, night sweats and vaginal dryness

 Add-back therapy with low-dose estrogen and progestins

(beyond 6 months of treatment)
 GnRH agonists

 The long-term use of GnRH agonists in abnormal bleeding

should be limited if other medical or surgical treatments are
contraindicated.

 the possible temporary “flare” or exacerbation of symptoms

immediately after GnRH injection
Selective progestrone receptor modulators(SPRM)
Selective progestrone receptor modulators (SPRM)

 Ulipristal acetate – the only SPRM to have been

licensed for use in clinical practice

 Tissue specific partial progesterone antagonist effect

and modulates the progesterone receptors in
endometrium and underlying myometrial tissue resulting
proapoptotic / antiproliferative effects on fibroid cells
Selective progestrone receptor modulators (SPRM)

 Control of heavy menstrual bleeding in 90% of women

 Amenorrhoea in over 70% of women
 Median times to amenorrhea: - 7 days for patients receiving 5
mg of ulipristal acetate
 Progestrone receptor modulator associated endometrial
changes (PAEC) - benign, non-physiological, non-proliferative,
histological features of the endometrium
 spontaneously reverse over a few weeks to months after
cessation of the 3-month UPA treatment.
Selective progestrone receptor modulators (SPRM)

 Median reduction in size of fibroids (12-36%)

 After treatment cessation, menstruation usually returns

within 4–5 weeks, but fibroid volume reduction can be
sustained for up to 6 months.

 Given as short-term (3 months) pretreatment of fibroid prior

to surgical removal (5-10mg daily)
Selective progestrone receptor modulators (SPRM)

 Minor reported side effects – headache (4%), breast

complaints (4%)

 Short-term use of SPRMs resulted in improved quality of

life, reduced menstrual bleeding and high rates of
amenorrhoea.

 No publication to date on the clinical utility of SPRMs in the

management of women with heavy menstrual bleeding
without fibroids
 Selective estrogen receptor modulators (SERM)

 Ormeloxifene is a selective estrogen receptor modulator,

which significantly inhibits endometrial proliferation and
increase haematocrit level among HMB women.

 With a dose of 60 mg twice a week

 Reduce the menstrual blood loss and endometrial thickness

by 85-97.7%

 after 3 months of treatment, 9.5% of the women reporting

amenorrhea
Selective estrogen receptor modulators (SERM)

 Side effects :- headache, GI upset, ovarian cyst

 Avoid in liver and renal disease, PCOS

 Benefit - cost effective, convenient dosage, any age

group, protective to breast and endometrium, use as
contraception

More RCTs required.

Medical treatment options for abnormal uterine
bleeding based on PALM-COEIN etiology

Etiology Treatment

AUB-P  Multiple polyps or polypoidal endometrium and

(Polyps) fertility is not desired– LNG-IUS can be
combined with surgical removal

AUB-A  LNG-IUS
(Adenomyosis)  If LNG IUS is not accepted– CHCs, NSAIDs,
progestins
 GnRH agonists with add back therapy
Medical treatment options for abnormal uterine
bleeding based on PALM-COEIN etiology
Etiology Treatment

AUB-L  Tranexamic acid or CHCs or NSAIDs, LNG-IUS

(Leiomyoma)
 In women >40 years of age, fertility is not desired,
short-term management (up to 6 months)– GnRH
agonists followed by hysterectomy

 In women <40 years of age, fertility is desired,

short-term management of GnRH agonists followed
by myomectomy

 Long-term GnRH with add-back therapy

 Newer medical options: SPRMs

Medical treatment options for abnormal uterine
bleeding based on PALM-COEIN etiology

Etiology Treatment

AUB-M Hyperplasia without atypia : -

(Malignancy and LNG-IUS
Endometrial oral progestins
Hyperplasia) SPRMs

AUB-C Tranexamic acid as primary option

(Coagulopathy) Hormonal treatment with CHCs/LNG-IUS as
secondary option
NSAIDs and injectables were contraindicated.
Medical treatment options for abnormal uterine
bleeding based on PALM-COEIN etiology

Etiology Treatment

AUB-O  In women desiring contraception; - COC, DMPA,

(Ovulatory and LNG-IUS
Dysfunction)
 In women with cyclic bleeding or predictable in
timing;- NSAIDs and antifibrinolytics

AUB-E Similar to management of AUB-O

(Endometrial)
Medical treatment options for abnormal uterine
bleeding based on PALM-COEIN etiology

Etiology Treatment
AUB-I  Medications causing AUB should be changed to
(Iatrogenic other alternatives
causes)  If no alternatives are available, LNG-IUS is
recommended.

AUB-N  Idiopathic AUB and desire effective contraception:-

(Not defined) LNG-IUS and CHCs
 Cyclic oral progestins (from day 5 to 26), are
recommended if CHCs are contraindicated.
 Cyclic bleeding :- NSAIDs and Tranexamic acid
 If medical and surgical treatment have failed or
contraindicated:- GnRH with add-back therapy
 References

Andersson, K., Odlind, V., Rybo, G. (1994) Levonorgestrel-releasing and

copper-releasing (Nova T) IUDs during five years of use: a randomized
comparative trial. Contraception 49(1), 56–72
Donnez, J., Tatarchuk, T.F. and Bouchard, P. (2012) Ulipristal acetate versus
Leuprolide Acetate for uterine fibroid, N. Engl. J. Med., 366, 421-32
Farrukh, J.B., Towriss, K., McKee,N. (2015) Abnormal uterine
bleeding;Taking the stress out of controlling the flow, Canadian Family
Physician Vol 61
Lethaby, A., Puscasiu, L., Vollenhoven., B (2017) Cochrane Database of
Systematic Reviews; Preoperativemedical therapy before surgery for
uterinefibroids
 References

Murji, A., Whitaker, L., Chow, T.L., Sobel, M.L. (2017) Cochrane Database of
Systematic Reviews; Selective progesterone receptormodulators
(SPRMs) for uterine fibroids
Maybin, J.A. and Critchley (2016) Medical management of heavy menstrual
bleeding, Womens health, 12(1), 27-34
NICE (2007) Heavy menstrual bleeding, clinical guidance 44
SOGC (2013) Abnormal uterine bleeding in pre-menopausal women,
Clinical practice guideline No. 292
Sriprasert, I. , Pakrashi, T., Kimble, T. and Archer, D.F. (2017) Heavy
menstrual bleeding diagnosis and medical management, Contraception
and Reproductive Medicine,(2)20