Treatment Goals of AUB
- Control bleeding
- Prevent recurrence
- Correct anaemia
- Improve quality of life
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Any interventions should aim to improve quality of life measures.
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Management options of AUB
Medical management
Surgical management
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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
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Medical management is the first line therapeutic option.
Medical treatment options
Non-hormonal treatment
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Hormonal treatment
Non-hormonal treatment
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Non-steroidal anti-inflammatory drugs (NSAIDs)
Mechanism of action
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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
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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.
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Non-steroidal anti-inflammatory drugs (NSAIDs)
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- Adverse effects : nausea, vomiting, abdominal pain, headache
- contraindications: women with bleeding disorders or platelet function abnormalities
Antifibrinolytic agent (Tranexamic acid)
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- 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)
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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
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Antifibrinolytic agent (Tranexamic acid)
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- 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.
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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.
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Hormonal treatment
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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
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Combination hormonal contraceptives (CHCs)
- excellent cycle control
- significantly reduce menstrual loss (up to 40% to 50%)
- improve dysmenorrhea
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Combination hormonal contraceptives (CHCs)
Types of CHCs
- oral contraceptive pill
- contraceptive patch
- vaginal ring
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All CHCs are effective in reduction of menstrual blood loss.
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Combined hormonal contraceptives (CHCs)
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
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Combination hormonal contraceptives (CHCs)
The possible side effects
Contraindications
- breast tenderness
- mood change
- headache
- nausea
- vomiting
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- women who are over 35 yrs old who smoke
- hypertension
- cardiovascular disease
- migraine with aura
- breast cancer
- venous thromboembolism or thrombogenic mutation
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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)
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Progestins
Oral progestin
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- 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
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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
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Progestins
Progestin intrauterine system (LNG-IUS)
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- First line of treatment in AUB (NICE, 2007)
Progestins (LNG-IUS)
Vertical stem: release daily doses of 20 micrograms of LNG
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Effects: -prevent endometrial proliferation -thicken cervical mucus -suppress ovulation
Reduction of MBL between 71-96% -benefit seen after 6 months
Requires an endometrial cavity that is 6 to 9 cm in length with minimal distortion
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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.
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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
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Progestins (LNG-IUS)
Drawback:
- high cost
- spontaneous expulsion (7%)
- uterine perforation (1:1000 cases)
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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
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Danazol
- Synthetic steroid with androgenic properties
- Anti-estrogenic and anti-progestogenic effect
- Can reduce the menstrual blood loss up to 80%
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Danazol
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- 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.
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Danazol
- significantly more adverse effects than other medical therapies
- should not be used routinely
- should be limited to 6 months
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GnRH agonists
Synthetic peptide that act like a natural GnRH but with longer biological half life
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GnRH agonists
Binds to GnRH receptor Decreased FSH and LH
No follicular development, estrogen production, no ovulation, no progeterone, no menses
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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
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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)
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GnRH agonists
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- 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)
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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
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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.
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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)
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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
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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
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Selective estrogen receptor modulators (SERM)
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- Side effects :- headache, Gl 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.
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Medical treatment options for abnormal uterine bleeding based on PALM-COEIN etiology
| Etiology | Treatment |
|---|---|
| AUB-P (Polyps) |
|
| AUB-A (Adenomyosis) |
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Medical treatment options for abnormal uterine bleeding based on PALM-COEIN etiology
| Etiology | Treatment |
|---|---|
| AUB-L (Leiomyoma) |
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Medical treatment options for abnormal uterine bleeding based on PALM-COEIN etiology
| Etiology | Treatment |
|---|---|
| AUB-M (Malignancy and Endometrial Hyperplasia) | Hyperplasia without atypia : -
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| AUB-C (Coagulopathy) |
|
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Medical treatment options for abnormal uterine bleeding based on PALM-COEIN etiology
| Etiology | Treatment |
|---|---|
| AUB-O (Ovulatory Dysfunction) |
|
| AUB-E (Endometrial) | Similar to management of AUB-O |
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Medical treatment options for abnormal uterine bleeding based on PALM-COEIN etiology
| Etiology | Treatment |
|---|---|
| AUB-I (Iatrogenic causes) |
|
| AUB-N (Not defined) |
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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
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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
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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
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This download link is referred from the post: MBBS Lecture Notes for all subjects (updated for 2021 syllabus) - All universities