Malignant disease of the uterus Flashcards by bushra gul

Since 1990, mortality from endometrial cancer has:

Decreased by 30%
Decreased by 10%
Increased by 25%
Increased by 33%
Increased by 50%

The answer is increased by 25%.

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What percentage of endometrial cancer is due to lifestyle and other known risk factors?

7%
17%
27%
37%
47%

37%

The answer is 37%. This is secondary to obesity and other risk factors, such as unopposed HRT usage.

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What is the peak age for developing endometrial cancer?

40–49 years old
50–59 years old
60–69 years old
70–79 years old
80–89 years old

70–79 years old

The answer is 70–79 years old.

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What is the incidence of endometrial cancer in the UK (per 100 000 women)?

70–79 years old

The answer is 70–79 years old.

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Regarding staging for endometrial cancer:

A - Pelvic lymph node involvement constitutes stage IIIC disease

B - Endocervical gland involvement is stage III disease

C - Lymphadenectomy is required to perform an adequate FIGO staging

D - Less than 50% of myometrial involvement defines FIGO stage IA

E - Positive peritoneal washings is stage IIIA

A - The answer is true. Pelvic lymph node involvement is stage IIIC1 disease. Involvement of the para-aortic nodes with or without pelvic nodes is stage IIIC2 disease.

B - The answer is false. Endocervical gland involvement and disease otherwise limited to the uterus is stage I disease and subclassified by the degree of myometrial invasion.

C - The answer is true. The role of lymphadenectomy in the management of endometrial cancer is under continual debate. The publication of the ASTEC study has not abated this. There will be regional and national variation in practice.

D - True

E - The answer is false. Peritoneal cytology is no longer a feature of staging for endometrial cancer. If performed, this is reported separately.

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Regarding prognostic factors of endometrial cancer,

A - Uterine size

B - Cervical involvement

C - Grade

A - The answer is false. Uterine size used to be part of the staging procedure; however, with the onset of accurate imaging of the uterus, this is no longer a variable.

B - The answer is true. This upstages the cancer to stage II.

C - The answer is true. This has a bearing on survival.

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Which of the following risk factors increase the likelihood of endometrial cancer?

Overweight/obesity

Diabetes

Smoking

Family history of hereditary non-polyposis coli (HNPCC)/Lynch II syndrome

Being nulliparous

A - true. owing to increased level of estrogen available in the postmenopausal woman and also the disruption of ovulatory cycles in the premenopausal woman.

B - true. This is owing to the enhancing effects of insulin and insulin-like growth factors on estrogen receptors in uterine tissue.

C - false because of antiestrogenic effects of nicotine.

D - true. There is a genetic link with colorectal and endometrial cancer in the Lynch II syndrome.

E - true. Nulliparous women have increased number of cycles and, thus, more exposure to unopposed estrogen.

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Which of the following risk factors increase the likelihood of endometrial cancer?

Low-dose estrogen combined oral contraception
A late menopause
Progestogen use

A - False. This actually decreases risk of endometrial cancer b/c of protective effect of combined oral contraceptive.

B - True. Women have an increased number of cycles and thus more exposure to unopposed estrogen.

C - False. This actually decreases the risk of endometrial cancer.

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Which of the following risk factors increase the likelihood of endometrial cancer?

Taking unopposed hormone replacement therapy

Taking tamoxifen

Polycystic ovary syndrome

A - True. Taking unopposed estrogen in the form of hormone replacement therapy increases the risk of endometrial cancer by 50%.

B - True. There is an excess of two in every 10 000 cases per year with tamoxifen usage.

C - True. There are many mechanisms where polycytic ovary syndrome patients have increased risks of endometrial cancer but predominantly the main cause of the risk is the increased number of anovulatory cycles and, therefore, increased exposure to unopposed estrogen.

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Concerning the prevalence of gynaecological malignancies:

Endometrial cancer is the fourth most common cancer in women in the UK, with over 9000 new cases per year

The most common female malignancy in women in the UK is breast cancer

The incidence of endometrial cancer has been falling with the introduction of cervical screening

The UK has the second highest incidence of endometrial cancer in the European Union

Cervical and vulval cancer are more prevalent in women in the UK than endometrial cancer

A - True. The incidence of breast cancer far outweighs that of endometrial cancer.

B - False. The incidence has actually increased over the last decade and cervical screening has little bearing on the detection of endometrial cancer.

C - False. There are a number of socioeconomic and possible ethnic reasons for this but it is unclear of the individual contribution of these factors.

D - The answer is false.

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Regarding the investigation of postmenopausal bleeding:

All patients should have an endometrial biopsy performed

In total, 20% of women seen in a postmenopausal bleeding clinic will have endometrial cancer

In total, 10% of women seen in a postmenopausal bleeding clinic will have endometrial cancer

Hysteroscopy should be performed as an outpatient procedure only

A - False. The risk of endometrial cancer falls in relation to the endometrial thickness measurement on ultrasound (e.g. if the endometrial thickness is less than 5 mm, then the risk of endometrial cancer being the diagnosis is less than 1%). Therefore, it would be acceptable not to perform endometrial sampling. (, this is dependent on local guidelines where the cut-off may be lower at 4 mm in order to decrease the risk of missing a cancer.)

B - True. This shows that over 90% of women with this symptom will not have a malignancy.

C - False. Where possible, outpatient assessment and sampling of the endometrium should be carried out (e.g. TVS, outpatient hysteroscopy or biopsy). However, if this is unsuccessful, then it may be necessary to perform these tests in terms of a hysteroscopy and curettage.

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The regression rate of complex atypical hyperplasia treated with progestogens

1 - 5 %
25 %
50- 75 %
60 %
90 %

The answer is 60%.

Simple hyperplasia: 1–5 Malignant potential (%)
Complex hyperplasia: 25 Malignant potential (%)
Atypical hyperplasia: 50–75 Malignant potential (%)

Untreated simple and complex hyperplasia

90 (spontaneous): Regression rate (%)
1–5: Progression rate (%)

Atypical hyperplasia** The degree of atypia correlates with regression rates after progesterone

60 (spontaneous): Regression rate (%)
25: Progression rate (%)

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The progression rate of complex atypical hyperplasia treated with progestogens

1 - 5 %
25 %
50- 75 %
60 %
90 %

The answer is 25%.

Simple hyperplasia: 1–5 Malignant potential (%)
Complex hyperplasia: 25 Malignant potential (%)
Atypical hyperplasia: 50–75 Malignant potential (%)

Untreated simple and complex hyperplasia

90 (spontaneous): Regression rate (%)
1–5: Progression rate (%)

Atypical hyperplasia** The degree of atypia correlates with regression rates after progesterone

60 (spontaneous): Regression rate (%)
25: Progression rate (%)

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The risk of malignancy in simple hyperplasia

1 - 5 %
25 %
50- 75 %
60 %
90 %

The answer is 1–5%.

Simple hyperplasia: 1–5 Malignant potential (%)
Complex hyperplasia: 25 Malignant potential (%)
Atypical hyperplasia: 50–75 Malignant potential (%)

Untreated simple and complex hyperplasia

90 (spontaneous): Regression rate (%)
1–5: Progression rate (%)

Atypical hyperplasia** The degree of atypia correlates with regression rates after progesterone

60 (spontaneous): Regression rate (%)
25: Progression rate (%)

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The malignant potential for complex atypical hyperplasia

1 - 5 %
25 %
50- 75 %
60 %
90 %

The answer is 50–75%.

Simple hyperplasia: 1–5 Malignant potential (%)
Complex hyperplasia: 25 Malignant potential (%)
Atypical hyperplasia: 50–75 Malignant potential (%)

Untreated simple and complex hyperplasia

90 (spontaneous): Regression rate (%)
1–5: Progression rate (%)

Atypical hyperplasia** The degree of atypia correlates with regression rates after progesterone

60 (spontaneous): Regression rate (%)
25: Progression rate (%)

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The rate of spontaneous regression for untreated simple hyperplasia

1 - 5 %
25 %
50- 75 %
60 %
90 %

The answer is 90%. For more information, see the tables later in this section.

Simple hyperplasia: 1–5 Malignant potential (%)
Complex hyperplasia: 25 Malignant potential (%)
Atypical hyperplasia: 50–75 Malignant potential (%)

Untreated simple and complex hyperplasia

90: spontaneous Regression rate (%)
1–5: Progression rate (%)

Atypical hyperplasia** The degree of atypia correlates with regression rates after progesterone

60: spontaneous Regression rate (%)
25: Progression rate (%)

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FIGO stages for endometrial cancer.
Histologically proven endometrial cancer, radiologically confined to the uterus. Treated by a standard hysterectomy and bilateral salpingoopherectomy. Pathology of the specimens showed an endometrioid carcinoma confined to the inner half of the myometrium; however, peritoneal washings were positive
1
1 A
1 B
2
3 A
3 B
3 C
3 C 1
3 C 2 
4 A 
4 B
Unable to satge

The answer is IA.

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FIGO stages for endometrial cancer.
At time of hysteroscopy, abnormal lesions were found in the uterus, at the cervix and also on the upper portion of vagina. An MRI scan did not show any pelvic spread otherwise. Biopsy of these lesions showed adenocarcinoma consistent with an endometrial origin
1
1 A
1 B
2
3 A
3 B
3 C
3 C 1
3 C 2 
4 A 
4 B
Unable to satge

The answer is IIIB.

FIGO stages for endometrial cancer.
Poorly differentiated endometrial cancer, which has invaded more than 50% of the myometrial thickness
1
1 A
1 B
2
3 A
3 B
3 C
3 C 1
3 C 2 
4 A 
4 B
Unable to satge

The answer is IB.

FIGO stages for endometrial cancer.
Well-differentiated endometrial cancer. Treated by a simple hysterectomy and is found to have a large pelvic lymph node, which is sampled and is found to contain metastatic cancer. No other evidence of distant metastases is found
1
1 A
1 B
2
3 A
3 B
3 C
3 C 1
3 C 2 
4 A 
4 B
Unable to satge

The answer is IIIC1.

In a case where endometrial cancer is confirmed but the woman is considered unfit for surgery, what are the options that are open to her?

A - Supportive and/or palliative treatment

B - Hormonal treatment

C - Radical radiotherapy

D - Palliative radiotherapy

All are true

A - However, the woman needs to be fully counselled with regards to the palliative nature of management.

B - Again, the woman needs to be counselled that this is not curative but palliative in intent.

C - If the tumour is thought to be early stage and amenable to surgery but medically unfit; however, each case has to be discussed on its merits and through the multidisciplinary team.

D - However, woman needs to be counselled on palliative intent and this is usually if woman is symptomatic with bleeding.

In relation to adjuvant treatment for endometrial cancer:

A - Postoperative adjuvant radiotherapy improves survival for the low- and medium-risk patients

B - Endometrial cancer recurrence has a good salvage rate with radiotherapy

C - Women who recur after adjuvant external-beam radiotherapy and brachytherapy can be retreated again with radiotherapy

A - FALSE
B - TRUE
C - FALSE

A - There is evidence to show that there is no survival benefit although there was a reduction in locoregional recurrences.

B - This is why the overall survival for women who do not receive adjuvant therapy is equal to those who do.

C - Once the maximum radical dose of radiotherapy has been administered the woman cannot be rechallenged with a further radical course of radiotherapy.

A woman returns to your clinic for a discussion of the pathology results of the TAH. An excerpt of a report reads as follows:

‘Poorly differentiated endometrioid adenocarcinoma invading more than half of the myometrium and extends to endocervical glands.’

Things to consider when answering the below:
1 - What is the stage and grade of the tumour and will she need further adjuvant therapy?
2 - If the cell type were a uterine serous papillary carcinoma, would there be any difference in the treatment?

Regarding adjuvant treatment for the aforementioned case:

The risk of recurrence and nodal metastases is low, and no further treatment is necessary

The answer is false. This woman is at high risk of recurrence and lymph node metastases are significant; therefore, adjuvant therapy should be offered.

A woman returns to your clinic for a discussion of the pathology results of the TAH. An excerpt of a report reads as follows:

‘Poorly differentiated endometrioid adenocarcinoma invading more than half of the myometrium and extends to endocervical glands.’

Regarding adjuvant treatment for the aforementioned case:

The risk of spread to the iliac nodes is in the region of 15–20%

The answer is true.

A woman returns to your clinic for a discussion of the pathology results of the TAH. An excerpt of a report reads as follows: 'Poorly differentiated endometrioid adenocarcinoma invading more than half of the myometrium and extends to endocervical glands.' Things to consider when answering the below: 1 - What is the stage and grade of the tumour and will she need further adjuvant therapy? 2 - If the cell type were a uterine serous papillary carcinoma, would there be any difference in the treatment? Regarding adjuvant treatment for the aforementioned case: Adjuvant concurrent chemoradiotherapy (in view of cervical disease) is the standard treatment in the UK

The answer is false. The role of concurrent chemoradiotherapy is currently unproven in this setting, although there is some early evidence of the use of chemotherapy as adjuvant treatment for endometrial cancer with poor prognostic markers. PORTEC 3, a randomised controlled trial will compare concurrent chemoradiottherapy vs radiotherapy as the standard arm, but has yet to publish their survival endpoints. In primary cervical cancer, there is clear evidence of the use of concurrent chemoradiotherapy for treatment but this differs from endometrial cancer.

TRUE Less than 10% of high-grade disease is limited to the endometrium with 15% extending to the cervix. Lymphovascular space invasion is present in 15% of stage I cancers but are associated with higher recurrence rates. Prognostic factors include grade/myometrial depth of involvement/endocervical involvement/cell type.

A woman returns to your clinic for a discussion of the pathology results of the TAH. An excerpt of a report reads as follows: 'Poorly differentiated endometrioid adenocarcinoma invading more than half of the myometrium and extends to endocervical glands.' Things to consider when answering the below: 1 - What is the stage and grade of the tumour and will she need further adjuvant therapy? 2 - If the cell type were a uterine serous papillary carcinoma, would there be any difference in the treatment? Regarding adjuvant treatment for the aforementioned case: The woman should be offered a re-laparotomy and pelvic lymphadenectomy

The answer is false. There is no role for re-laparotomy and pelvic lymphadenectomy as this does not improve survival.

Unfortunately, despite radical radiotherapy the woman developed vaginal bleeding 1 year later and a mass was found on clinical examination. She is very disappointed and wants to know what options, if any, are open to her. Which of the following modalities would you organise as first line to assess this mass? ``` A - CT scan of the abdomen and pelvis B - Transvaginal scan C - MRI scan of the abdomen and pelvis D - PET scan E - Examination under anaesthetic ```

Only Examination under anaesthetic & MRI scan of the abdomen and pelvis A - The CT scan may help with ruling out distant metastases, but due to difficulties defining the tumour mass from surrounding structures, it may only provide limited information within the pelvis. C - The MRI scan provides the best definition of the mass and possible invasion into surrounding tissue. It also provides information about the feasibility of further surgery. D - PET scanning in this situation still remains experimental, although it may have a major role in the future. E - The EUA will allow pathological confirmation of a recurrence and allow the resectability of the tumour to be assessed clinically.

Unfortunately despite radical radiotherapy, the woman developed a vault recurrence 1 year later. She is very disappointed and wants to know what options, if any, are open to her. Consider carefully what these are and how you would decide which course of action you would take in this unfortunate case. Once the recurrence is proven, what curative options are open to the woman? ``` A - More radiotherapy B - Chemotherapy C - Hormone therapy D - Supportive treatment only E - Exenterative surgery ```

Only Exenterative surgery true A - Further radical radiotherapy would not be possible as it would exceed the maximum dose tolerable. E - The answer is true. The only curative option is exenterative surgery where distant disease has been excluded. In this case, the patient has to be deemed mentally and physically capable of coping with the trauma of major surgery and the urinary and bowel diversion. Also, at the time of surgery, further nodal sampling should be performed with intraoperative pathology to exclude nodal metastases.

A 56-year-old woman has a high body mass index of 50 and presented to her doctor with worsening abdominal pain and a feeling of fullness. Her doctor organised an ultrasound scan, which demonstrated a large mass filling her pelvis and extending to the level of her umbilicus. She then admits to having a fibroid discovered 10 years ago when she experienced menstrual dysfunction (an ultrasound report showed that it measured 10 cm at that stage). Given her history, answer the following questions from the given choices. What would be the management for this woman?

The answer is laparotomy. The mass requires assessment and resection. There is a role of percutaneous biopsy, if it was felt that the patient was too high risk to undergo surery.

The answer is chest x-ray. It would exclude pulmonary metastases.

Whole-body CT scan The answer is whole-body CT scan. It would be able to assess the pelvis and abdomen quickly and help differentiate the primary tumour, as well as exclude distant metastases.

The same woman from Case study 2 was found to have a leiomyosarcoma of the uterus, which was adherent to the small bowel within the pelvis and also to the omentum. The liver/upper abdomen was otherwise clear. There was no radiological pathological lymph nodes present. She underwent a subtotal hysterectomy and bilateral salpingo-oophorectomy and small bowel resection and omentectomy. There was no residual disease present at the end of the procedure. A - What is the stage of this woman? B - She has a good overall prognosis C - Pelvic lymphadenectomy is indicated in this case D - A bilateral salpingo-oophorectomy for normal-looking uninvolved ovaries would still be indicated if the woman was only 35 years of age

A - Stage IIIA B -The answer is false. Her prognosis of 5-year survival will be less than 10%. C - The answer is false. It metastasises via the haematogenous route. D - The answer is false. Ovarian conservation in these cases does not appear to alter survival and would be beneficial in the premenopausal women.

Leiomyosarcomas are more likely to occur in an older population compared with carcinosarcomas

The answer is false. Leiomyosarcomas are more likely to occur in a younger population, with a median age of 48–52 years versus 62–67 years.

Uterine sarcomas represent a third of all uterine malignancy

The answer is false. Uterine sarcomas represent only 4–9% of all invasive uterine cancers - Sarcomas have a more aggressive clinical behaviour with a poor prognosis. - Surgery remains the mainstay of treatment for the majority of the sarcomas. - There is a limited role for adjuvant radiotherapy/chemotherapy.

The treatment of leiomyosarcomas is largely surgical

The answer is true. The mainstay of treatment is a total abdominal hysterectomy and bilateral salpingo-oophorectomy.

It is essential to perform a pelvic and para-aortic lymphadenectomy in all cases of leiomyosarcoma

The answer is false. It is not indicated in these tumours as the mode of spread is largely haematogenous.

The prevalence of uterine sarcomas is twice as high in the black female population compared with the white female population

The answer is true. However there is no survival difference. For more information, refer back to the section on Epidemiology and prognostic factors (link is external).

A 51-year-old woman presents with a 2 month history of postmenopausal bleeding. Her periods stopped last year and she has been using continuous combined hormone replacement therapy for 9 months. A transvaginal ultrasound scan revealed a normal-size anteverted uterus with normal ovaries and an endometrial thickness of 3 mm. Clinical examination was unremarkable. What is the most appropriate management? Cervical smear Change to cyclical hormone replacement therapy without performing further investigation Endometrial biopsy Inpatient hysteroscopy To cease hormone replacement therapy and investigate further if symptoms persist beyond 6 weeks

To cease hormone replacement therapy and investigate further if symptoms persist beyond 6 weeks The correct answer is to cease hormone replacement therapy (HRT) and investigate further if symptoms persist beyond 6 weeks. Continuous combined HRT preparations are not suitable for use in the perimenopause or within 12 months of the last menstrual period. Women who use such preparations are likely to suffer irregular bleeding and should consider changing to cyclical HRT. In this case, the bleeding is likely to be related to HRT use. If, following cessation of the HRT, bleeding persists beyond 6 weeks, further endometrial assessment would be indicated. Otherwise, assuming the bleeding stops, the preparation could be changed to a cyclical preparation.

A 65-year-old woman with a BMI of 40, early menarche, late menopause and Type 2 diabetes mellitus presents with postmenopausal bleeding. The exit cervical cytology was normal. She has previously had a cone biopsy and is known to have cervical stenosis. An ultrasound scan of her uterus reveals an endometrial thickness of 20 mm. Both pipelle biopsy in the clinic and general anesthesia hysteroscopy and biopsy were unsuccessful due to cervical stenosis. - What further step would you discuss with the woman? - MRI of the pelvis - Offer hysterectomy and bilateral salpingo-oophorectomy - Oral progesterone - Repeat the cervical cytology - Weight loss regime

Offer hysterectomy and bilateral salpingo-oophorectomy The correct answer is offer hysterectomy and bilateral salpingo-oophorectomy (BSO). Although a weight loss regime would be beneficial to general health, the risk of an endometrial cancer in this woman is high, given her risk factors and thickened endometrium. It would be prudent to offer hysterectomy and BSO, given the diagnostic uncertainty in this situation. An MRI of the pelvis would not help obtain the histology ultimately needed to diagnose the woman.

A 66-year-old woman presents to the GP with 2 weeks of bleeding. Her last period was at the age of 54. Past medical history includes chronic hypertension treated with Atenolol. She had one child at the age of 28 and is obese with a BMI of 32 kg/m2. She had a 2-week referral for gynaecology outpatient where she had a Pipelle biopsy. The results of the latter, ultrasound and CT scan confirm endometrial carcinoma confined to the endometrium with less than half of the myometrium invaded. She is understandably devastated but very keen to discuss management with you. - Which of the following options is unsuitable within her current management plan? - Total abdominal hysterectomy - Total laparoscopic hysterectomy and bilateral salpingo-oophorectomy - Inspection and palpation of the omentum and pelvic and para-aortic lymph nodes - Peritoneal lavage for cytology - Radiotherapy

Radiotherapy The answer is radiotherapy. The peak incidence of endometrial cancer is between 65 and 75 years of age, with a two- to four-times increased risk when menopause occurs over 52 years of age (compared with menopause before 49 years of age). Endometrial cancer is one of the cancers most strongly associated with obesity. Stage I endometrial cancer is carcinoma confined to the corpus uteri: IA confined to endometrium with no, or less than half myometrium invaded IB invasion equal to, or more than half of myometrium. The recommended primary treatment for stage I endometrial cancer is complete surgical staging, which encompasses laparotomy or laparoscopy with peritoneal lavage for cytology and careful inspection and or palpation of the abdomen and pelvis (diaphragm, liver, omentum, pelvic and para-aortic lymph nodes, pelvic and bowel peritoneal surfaces). This would be followed by total (abdominal or laparoscopic) hysterectomy and BSO as microscopic metastases can be present. TLH and BSO can be considered in centres with expertise. TLH has become the standard approach in recent years for early stage endometrial cancer. A number of large trials have shown either equivalent or less intra-operative complications, less blood loss and reduced hospital stay at the expense of longer operating time compared to total abdominal hysterectomy. Furthermore, the laparoscopic approach has been shown to offer improved quality of life and reduced cost when everything has been considered. Treatment by hysterectomy alone or hysterectomy and radiation have better prognosis than women treated by radiotherapy alone. It is important to note that the question asks 'initial' management plan. Radiotherapy may be considered later, but unlike cervical cancer, it is important for this woman to first have all the other options, including TLH + BSO, peritoneal lavage and inspection and palpation of the abdomen and pelvis.

A 60-year-old post menopausal women who is using tamoxifen for breast cancer presents with history of postmenopausal bleeding. A transvaginal USS showed an endometrial thickness of 5 mm. What is the best course of action? - Gel instillation sonography - Outpatient hysteroscopy with targeted endometrial biopsy - Pipelle biopsy in clinic - Repeat USS after 8 weeks - Saline hysterosonography

Outpatient hysteroscopy with targeted endometrial biopsy The answer is outpatient hysteroscopy with targeted endometrial biopsy. All abnormal bleeding or spotting should be investigated, but pipelle endometrial biopsy rarely provides useful diagnostic information in women treated with tamoxifen because it induces epithelial stromal hypertrophy. This can result in obtaining a small amount of tissue that is not suitable for diagnosis, especially in women with an endometrial thickness of less then 7 mm. Symptomatic women with a thickened endometrium should be investigated with hysteroscopy and targeted biopsy.

A 38-year-old woman with intermenstrual bleeding had an endometrial biopsy that has been reported as simple hyperplasia. What is characteristically associated with this diagnosis? - Anovulatory cycles - Hypethyroidism - Hypothyroidism - Hyperprolactinaemia - Vagina adenosis

Anovulatory cycles The correct answer is anovulatory cycles. Women <40 years of age who are diagnosed with simple, complex and atypical endometrial hyperplasia have been shown to have a history of polycystic ovary syndrome (anovulatory cycles) in 26%, 47% and 28% of cases, respectively.