Office hysteroscopy in postmenopausal women on HRT with uterine bleeding

1
Office hysteroscopy in postmenopausal women on
HRT with uterine bleeding

• Branka Žegura
• Gynecologic Clinic,
• University Clinical Centre Maribor, Slovenia
• Brijuni 11.9.2011

2
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.

3
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

4
AUB and HRT

• Unscheduled bleeding is most common in the
  initial months and tends to settle with long-term
  use.

5
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

6
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

7
HRT and endometrial hyperplasia

• Sequential HRT - 2.7 - 5 in over 3 years.
• Combined continuous HRT - lt1
• Sturdee DW. Br J Obstet Gynecol 2001

8
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

9
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.

10
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 11000 to 101000
• 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.

11
Combined HRT

• Relative risk for endometrial cancer
• Sequential
• progestogen lt10 days 2
• progestogen gt10 days 1,3
• 12 to 14 days of progestogen for the protection
  of endometrium.
• Continuous 0,9

12
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 2-year
  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.

14
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 344979-82.

15
Continuous HRT

• no endometrial hyperplasia after 3 years CEEMPA
• 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 E2NETA atrophic endometriom at
  hysteroscopy
• Piegsa K et al. Endometrial status in
  postmenopausal women on long term continuous
  combined HRT. Eur J Obstet Gynecol 1997
  72175-80.
• 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 (gt5 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.

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Combined HRT and endometrial cancer
17
AUB and HRT

• At hysteroscopy (HSC) the majority of combined
  HRT users will have no intrauterine pathology.
• Hickey M. Menopause International 2007

18
Hickey M. Maturitas 2009.
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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
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Office hysteroscopy

• no anaesthesia
• vaginoscopic approach/atraumatic insertion
  technique
• no cervical dilatation
• no additional costs, no operative theatre
• diagnostic and operative procedure,
• see and treat procedure (gt90),
• fast patients recovery,
• reduced complications,
• few limitations

21
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)

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Office operative hysteroscopy

• 1. biopsy
• 2. polipectomy
• 3. miomectomy (max. 1.5 cm)
• 4. metroplasty
• 5. sinechiolysis
• 6. tubal sterilization

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• 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

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• 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 non-users),
  office HSC
• endometrial polyp 23.7 (users) vs. 30.8
  (non-users), myoma 6.8 (users) vs. 11
  (non-users)
• intrauterine disease is more frequent in
  postmenopausal women who do not use HRT

25

• 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 non-users),
  office HSC
• higher incidence of endometrial carcinoma in
  non-users (RRgt10)
• protective effect of HRT on the endometrium

26

• 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 (gt5 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

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• 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

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• 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

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Office hysteroscopy - Maribor

• Dec 2010 - July 2011
• 43 women
• mean age 57.18 years (45-60 years)
• 68.7 continuous combined HRT

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Instrumentation

• 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)

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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)

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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

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Thank you!
Hvala!