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Office hysteroscopy in
postmenopausal women on HRT
with uterine bleeding
Branka Žegura
Gynecologic Clinic,
University Clinical Centre
Maribor, Slovenia
Brijuni; 11.9.2011
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AUB and HRT
Abnormal uterine bleeding
(AUB) with HRT is unscheduled
bleeding.
It affects around 40 to 60% on
combined HRT.
Commonly leads to
discontinuation of the therapy.
Hickey M. Maturitas 2009.
AUB and HRT
AUB occurs with cyclical and
continuous combined regimens.
38% on sequential and 41% on
combined HRT in one year.
12% and 20%, respectively
require endometrial biopsy.
Ettinger B. Fertil Steril 1998
AUB and HRT
Unscheduled bleeding is most
common in the initial months and
tends to settle with long-term
use.
Mechanisms of endometrial
bleeding and combined HRT
•wide range of combined HRT
•varying prescribing schedules
•no correlation between endometrial
histology with the type or dose of
HRT
•individual variations in response to
the same HRT
AUB and HRT
•poor compliance
•systemic or pelvic pathology
•40% of women with endometrial
polyps and sub mucus fibroids
•in the majority - no pathological
cause for the bleeding
HRT and endometrial
hyperplasia
Sequential HRT - 2.7 - 5% in
over 3 years.
Combined continuous HRT - <1%
Sturdee DW. Br J Obstet Gynecol 2001
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Unopposed estrogen and
endometrial carcinoma (ERT)
•RR 2,8
•duration of treatment
•increased risk persists for up to
15 years after treatment
•dosage
•type of estrogen - no difference
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Duration of treatment (ERT)
•in 10% endometrial hyperplasia
after 1 year of ERT
•50% after 2 years
•62% after 3 years, 50% complex
or atypical
The Writing Group for PEPI Trial. Effects of HRT on
endometrial histology in postmenopausal women. The PEPI trial.
J Am Assoc 1996; 275: 370-5.
Duration of therapy (ERT)
•after 4 months of ERT, simple endometrial
hyperplasia progresses to atypical.
Kurman RJ at al. The behaviour of endometrial hyperplasia. A long-term
untreated hyperplasia in 170 patients. Cancer 1985; 56 (2): 403-12.
•10 years of ERT increases the incidence of
endometrial cancer from 1:1000 to 10:1000
Shapiro S et al. Risk of localized and widespread endometrial cancer in relation
to recent and discontinued use of conjugated estrogens. New Engl J Med 1985;
313 (16): 969-72.
Combined HRT
Relative risk for endometrial cancer
Sequential:
progestogen <10 days: 2
progestogen >10 days: 1,3
12 to 14 days of progestogen for the
protection of endometrium.
Continuous: 0,9
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The safety of sequential HRT
•3 years study: protective effect of 10 mg MPA or
200 mg micronised progesterone
•1 year study: protective effect of 5 mg MPA
The Writing Group for PEPI Trial. Effects of HRT on endometrial histology in
postmenopausal women. The PEPI trial. J Am Assoc 1996; 275: 370-5.
•2 year study: protective effect of 10 mg
didrogesterone
Van der Mooren MJ et al. Changes in the withdrawal bleeding pattern and endometrial
histology during 17ßestradiol-dydrogesterone therapy in postmenopausal women: a 2year prospective study. Maturitas 1995; 20: 175-80.
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After 5 Years?
•2,5 fold increased risk
Beresford SAA et al. Risk of endometrial cancer in relation to use of estrogen
combined with cyclic progestagen therapy in postmenopausal women. Lancet 1997; 349:
458-61.
•RR 2,9 for progesterone and RR 0,9 for
testosterone derivatives
Weiderpass E et al. Risk of endometrial cancer following estrogen replacement with and
without progestins. J Natl Cancer Inst 1999; 91 (13): 1131-7.
•no increased risk (RR 1,07)
Pike MC et al. Estrogen-progestin replacement therapy and endometrial cancer. J Natl
Cancer Inst 1997; 89 (15): 1110-6.
Long-cycle progestogen regimens
•progestogen is added every 3 to 6 months
•15% of endometral hyperplasia after 3 months
•the addition of progestogen reverses hyperplasia,
but 2% remains after 2 years
•Scandinavian Long-Cycle study prematurely
terminated
Sturdee DW et al. Is timing of withdrawal bleeding a guide to endometrial safety
during sequential oestro-progestagen replacement therapy? Lancer 1994; 344:979-82.
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Continuous HRT
• no endometrial hyperplasia after 3 years CEE+MPA
The Writing Group for PEPI Trial. Effects of HRT on endometrial histology in postmenopausal women.
The PEPI trial. J Am Assoc 1996; 275: 370-5.
• after 1 year of E2+NETA atrophic endometriom at
hysteroscopy
Piegsa K et al. Endometrial status in postmenopausal women on long term continuous
combined HRT. Eur J Obstet Gynecol 1997; 72:175-80.
• decreased risk f endometrial cancer (RR 0,2)
Weiderpass E et al. Risk of endometrial cancer following estrogen replacement with and without
progestins. J Natl Cancer Inst 1999; 91 (13): 1131-7.
• WHI: decreased risk for endometrial cancer
Anderson GL et al. Effects of estrogen plus progestin on gynaecologic cancers and associated
diagnostic procedures. JAMA 2003; 290 (13): 1739-48.
• long term therapy (>5 years)
Pike MC et al. Estrogen-progestin replacement therapy and endometrial cancer. J Natl Cancer Inst
1997; 89 (15): 1110-6.
Hill et al. Continuous combined hormone replacement therapy and risk of endometrial cancer. Am J
Obstet Gynecol 2000; 183: 1456-61.
Combined HRT and endometrial
cancer
AUB and HRT
At hysteroscopy (HSC) the
majority of combined HRT users
will have no intrauterine
pathology.
Hickey M. Menopause International 2007
Hickey M. Maturitas 2009.
Management of AUB
• transvaginal ultrasonography
• saline infusion sonohysterography
• the gold standard is hysteroscopy with
endometral biopsy
• no evidence that changing the estrogen or
progestogen or the mode of delivery are
effective
•lack of consensus
•persistent bleeding
•when to reinvestigate?
Hickey M. Maturitas 2009
Office hysteroscopy
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no anaesthesia
vaginoscopic approach/atraumatic insertion technique
no cervical dilatation
no additional costs, no operative theatre
diagnostic and operative procedure,
see and treat procedure (>90%),
fast patient’s recovery,
reduced complications,
few limitations
Office hysteroscopy
• the diagnostic accuracy of HSC is high for
endometrial cancer and focal lesions (Clark TJ. JAMA
2002)
• 92% sensitivity and 82% specificity for diagnosis
of endometral polyps (Dueholm M. Fertil Steril 2011)
• 10% asymptomatic postmenopausal women with
normal ultrasound had endometrial pathology on
office HSC (Marello J Am Assoc Gynecol Laparosc 2000)
• PPV of office HSC in postmenopausal women with
thickened endometrium is 97% and NPV 100% (Lozzi
V. J Am Assoc Gynecol Laparosc 2000)
Office operative hysteroscopy
1. biopsy
2. polipectomy
3. miomectomy (max. 1.5 cm)
4. metroplasty
5. sinechiolysis
6. tubal sterilization
Outcome of outpatient micro-hysteroscopy
performed for abnormal bleeding while on
hormone replacement therapy
Okeahialam MG et al. J Obst Gyn 2001
•190 women with AUB on HRT, office HSC
•48.4% normal uterine cavity, 20% atrophic
endometrium, 27.4% endometrial polyp, 0.5%
myoma, 2.63% endometrial hyperplasia, 1.58%
adenocarcinoma
Hysteroscopic findings in postmenopausal
AUB: a comparison between HRT users and
non-users
Perone G et al. Maturitas 2002
•410 women with AUB (94 users, 191 nonusers), office HSC
•endometrial polyp 23.7% (users) vs. 30.8%
(non-users), myoma 6.8% (users) vs. 11% (nonusers)
•intrauterine disease is more frequent in
postmenopausal women who do not use HRT
The value of outpatient hysteroscopy in
diagnosing endometrial pathology in
postmenopausal women with and without HRT
Elliot J et al. Acta Obstet Gynecol 2003
•503 women with AUB (204 users, 299 nonusers), office HSC
•higher incidence of endometrial carcinoma in
non-users (RR>10)
•protective effect of HRT on the endometrium
HRT and evaluation of intrauterine pathology
in postmenopausal women: a ten year study
Mossa B et al. Eur J Gynaecol Oncol 2003
•587 women, 16.7% HRT users, office HSC
•HRT users had signif. increased endometrial
thickness (>5 mm) and higher incidence of AUB
•no difference in the incidence of endometral
carcinoma between HRT users and non-users
•cut-off point for HSC - endometrial thickness
of 8 mm in HRT users
Intrauterine pathology in women with abnormal
uterine bleeding taking HRT
Leung PL et al. J Am Assoc Gynecol Laparosc 2003
•99 women with AUB, office HSC
•18.6% intrauterine pathology
•4 times higher frequency of intrauterine pathology in
those with AUB after achieving amenorrhea
•higher frequency of intrauterine pathology when AUB
lasted for more 6 months
•office hysterocopy with endometrial biopsy if AUB
continues after 6 months of HRT or if it recurs after
amenorrhea
Do we really need to hysteroscope all women
who have irregular bleeding on HRT?
Lalchandani S. Gynecol Surg 2004
•77 women with AUB, office HSC
•14% endometrial polyp
•low incidence of significant pathology
•recommendation: office hysteroscopy where
facilities are available, if not ultrasonography
Office hysteroscopy - Maribor
• Dec 2010 - July 2011
• 43 women
• mean age 57.18 years
(45-60 years)
• 68.7% continuous
combined HRT
Instrumentation
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3 mm telescope, 30o fore-oblique
lens (Olympus)
4.5, 5.5 continuous-flow sheath
3 Fr, 5 Fr operative channel
grasping forceps, scissors
high-intensity xenon cold-light
source
Gynecare Versacsope system
(Alphacsope 1,9 mm hystroscope)
Gynecare Versapoint system
(bipolar 5Fr electrodes)
AUB and HRT
1. Normal uterine cavity (50.4%)
2. Abnormal uterine cavity:
• endometrial polyps (36.8%),
• myomas (10.2%)
3. Intracervical pathology:
• cervical polyp (2.6%)
Conclusions
The incidence of significant pathology in
patients with AUB on HRT is very low.
However benign polyps are common.
The gold standard for investigation of AUB is
HSC with endometrial biopsy, if AUB continues
after 6 months of HRT or if it recurs after
amenorrhea
Hvala!
Thank you!
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