Amenorrhoea MCQs

Explanation: Premature Ovarian Insufficiency (POI), previously known as premature ovarian failure, has several causes:

• A (Incorrect): 17-alpha-hydroxylase deficiency is a form of congenital adrenal hyperplasia causing primary amenorrhea and hypertension, not typically POI.
• B (Incorrect): Multiparity (having multiple births) is not a recognized cause of POI.
• C (Correct): Fragile X premutation carriers are at increased risk of developing POI.
• D (Incorrect): Polycystic Ovarian Syndrome (PCOS) is associated with anovulation but not typically premature depletion of ovarian follicles; women with PCOS may experience menopause later.
• E (Correct): Turner’s syndrome (45,X and variants) involves gonadal dysgenesis, leading to primary ovarian failure, which manifests as primary amenorrhea or POI.

Other causes include autoimmune disorders, chemotherapy, radiotherapy, and idiopathic factors. (NICE NG23)

References:

• NICE NG23: Menopause: diagnosis and management (Published Nov 2015, last updated Dec 2019)

Explanation: Low FSH and LH levels indicate hypogonadotropic hypogonadism, meaning the problem originates in the hypothalamus or pituitary gland.

• A (Correct): Combined oral contraceptive pills suppress gonadotropin (FSH and LH) secretion from the pituitary gland, leading to amenorrhea.
• B (Incorrect): Polycystic Ovarian Syndrome (PCOS) is typically associated with normal or low FSH and elevated LH levels.
• C (Incorrect): Pregnancy causes amenorrhea, but it is associated with high hCG levels, which maintain the corpus luteum; FSH and LH are suppressed. However, low FSH/LH isn’t the primary diagnostic hormonal feature.
• D (Incorrect): Premature Ovarian Failure (POF) or Insufficiency (POI) is characterized by high FSH and LH levels due to ovarian failure.
• E (Correct): Sheehan’s syndrome, resulting from pituitary ischemia/necrosis (often postpartum), leads to hypopituitarism, causing deficiencies in pituitary hormones, including FSH and LH.

Explanation: The patient presents with secondary amenorrhea, galactorrhea, and headache, accompanied by a very high serum prolactin level (4584 mIU/L; typical reference range <400-500 mIU/L). This strongly suggests a pituitary prolactinoma.

• A (Correct): An MRI scan of the brain/pituitary gland is the definitive investigation to confirm the presence of a pituitary adenoma, assess its size (micro- vs. macroadenoma), and its relationship to surrounding structures like the optic chiasm. NICE CKS recommends pituitary imaging for significantly elevated prolactin.
• B (Incorrect): Perimetry (visual field testing) is indicated if a macroadenoma is found on MRI or if the patient reports visual symptoms, but it is not the primary diagnostic imaging step.
• C (Incorrect): Serum FSH and LH levels may be suppressed by high prolactin but are not the priority investigation now.
• D (Incorrect): A transvaginal scan is irrelevant for investigating a suspected pituitary tumour.
• E (Incorrect): X-ray of the skull is an outdated and insensitive method for pituitary evaluation compared to MRI.

References:

• NICE CKS: Amenorrhoea (Last revised Nov 2022)
• NICE CKS: Hyperprolactinaemia (Last revised Sep 2023)

Explanation: Polycystic Ovarian Syndrome (PCOS) is characterized by several hormonal imbalances:

• A (Correct): Insulin resistance is common in PCOS, leading to compensatory hyperinsulinemia (elevated plasma insulin levels).
• B (Incorrect): Cortisol levels are typically normal in PCOS, although stress response might be altered.
• C (Correct): Luteinizing Hormone (LH) levels are often elevated, and the LH:FSH ratio is frequently increased (>2 or 3:1), although this is not part of the formal Rotterdam diagnostic criteria anymore but remains a common feature.
• D (Incorrect): Thyroid Stimulating Hormone (TSH) is usually normal; thyroid dysfunction should be excluded as it can mimic PCOS symptoms.
• E (Incorrect): Sex Hormone-Binding Globulin (SHBG) levels are typically decreased in PCOS, partly due to hyperinsulinemia and hyperandrogenism, leading to higher levels of free, biologically active androgens.

References:

• NICE Guideline NG89: Polycystic ovary syndrome: investigation and management (Published Sep 2018)

Explanation: This patient presents with classic features of PCOS (irregular cycles, hirsutism, obesity). As she is getting married soon and concerned about appearance (likely hirsutism), management should address symptoms effectively in the short term, alongside long-term health.

• A (Incorrect): Cyproterone acetate is an anti-androgen, effective for hirsutism, but often used in combination with estrogen (like in Dianette/co-cyprindiol) or as second-line. Starting it alone might not regulate cycles effectively.
• B (Incorrect): Metformin addresses insulin resistance but is less effective for hirsutism or cycle control compared to COCPs.
• C (Incorrect): Ovarian drilling is a surgical fertility treatment.
• D (Incorrect): While exercise and weight reduction are crucial long-term (and she is obese with BMI 30), they may not provide sufficient improvement in hirsutism or cycle control within 3 months to address her immediate pre-marital concerns.
• E (Correct): The Combined Oral Contraceptive Pill (COCP) is a first-line treatment for PCOS in women not seeking pregnancy. It effectively regulates menstrual cycles and manages hyperandrogenic symptoms like hirsutism and acne by suppressing ovarian androgen production and increasing SHBG. This would be the most appropriate option to quickly address her irregular bleeding and appearance concerns before her marriage.

References:

• NICE Guideline NG89: Polycystic ovary syndrome: investigation and management (Published Sep 2018)

Explanation: This scenario (secondary amenorrhea, headaches, galactorrhea) is strongly suggestive of hyperprolactinemia.

• A (Incorrect): Mammogram is for breast cancer screening/investigation, not relevant for galactorrhea workup initially.
• B (Correct): Serum prolactin measurement is the key initial investigation to confirm or refute hyperprolactinemia as the cause of the symptoms.
• C (Incorrect): Serum TSH is important to check (as hypothyroidism can cause mild hyperprolactinemia), but checking prolactin directly addresses the primary suspicion.
• D (Incorrect): MRI brain & pituitary is indicated *if* serum prolactin is significantly elevated, but it is not the *initial* blood test.
• E (Incorrect): Testing of visual fields is done if pituitary imaging reveals a macroadenoma threatening the optic chiasm, not as an initial step.

References:

• NICE CKS: Amenorrhoea (Last revised Nov 2022)
• NICE CKS: Hyperprolactinaemia (Last revised Sep 2023)

Explanation: This scenario implies the presence of estrogen (for breast development) but absence of menstruation. Causes can be anatomical outflow obstructions or specific genetic conditions.

• A (Correct): Androgen Insensitivity Syndrome (AIS) (46,XY) results in female external genitalia and breast development (due to aromatization of androgens) but absence of Mullerian structures (uterus) and typically sparse pubic/axillary hair.
• B (Incorrect): Gonadal agenesis (absence of gonads) results in lack of sex hormone production, leading to absent secondary sexual characteristics (infantile phenotype).
• C (Correct): Imperforate hymen is an anatomical obstruction preventing menstrual flow, presenting with primary amenorrhea, normal secondary sexual development, and often cyclical lower abdominal pain due to hematocolpos.
• D (Incorrect): Kallmann syndrome is characterized by hypogonadotropic hypogonadism (low FSH/LH) and anosmia, leading to absent or delayed puberty and lack of secondary sexual characteristics.
• E (Correct): Mullerian agenesis (Mayer-Rokitansky-Küster-Hauser syndrome, MRKH) (46,XX) involves congenital absence of the uterus and upper vagina. Ovarian function is normal, so secondary sexual characteristics develop, but menstruation cannot occur.

Explanation: Anovulation (absence of ovulation) is a common cause of infertility and irregular cycles.

• A (Incorrect): A Body Mass Index (BMI) of 20 kg/m2 is within the normal range and generally associated with regular ovulation, although extremes of weight (both low and high) can cause anovulation.
• B (Correct): Breastfeeding (lactation) causes elevated prolactin levels, which suppress GnRH pulsatility and gonadotropin release, leading to lactational amenorrhea and anovulation.
• C (Incorrect): Endometriosis causes pain and inflammation and can affect fertility through various mechanisms (e.g., anatomical distortion, inflammation), but it doesn’t typically cause anovulation directly unless associated with significant ovarian damage (e.g., large endometriomas).
• D (Incorrect): The Levonorgestrel-containing intrauterine system (LNG-IUS, e.g., Mirena) primarily works by thickening cervical mucus and thinning the endometrium. While it can variably affect ovulation, complete suppression is not consistent, and many users continue to ovulate. Its main effect causing amenorrhea/oligomenorrhea is local endometrial suppression, not central anovulation.
• E (Correct): Polycystic Ovarian Syndrome (PCOS) is the most common cause of chronic anovulation, characterized by hormonal imbalances disrupting follicular development and ovulation.

Other causes include hypothalamic amenorrhea, hyperprolactinemia, thyroid dysfunction, and premature ovarian insufficiency.

Explanation: Androgen Insensitivity Syndrome (AIS) occurs in individuals with a 46,XY karyotype whose tissues are unresponsive to androgens.

• A (Correct): Androgens normally suppress Mullerian duct development. In AIS, due to androgen resistance, anti-Müllerian hormone (AMH) produced by the testes still functions, leading to regression of Mullerian structures (uterus, fallopian tubes, upper vagina).
• B (Incorrect): Breast development occurs and is often normal to large because testosterone is aromatized to estrogen, which is unopposed due to androgen resistance.
• C (Correct): Testes develop under the influence of the SRY gene but fail to descend normally due to androgen resistance; they may be found in the abdomen, inguinal canal, or labia.
• D (Correct): Pubic and axillary hair growth is androgen-dependent, so it is typically sparse or absent in complete AIS (CAIS).
• E (Incorrect): Individuals with AIS are typically of normal or tall stature for females, not short stature.

Explanation: This patient presents with subfertility, secondary amenorrhea, headaches, and galactorrhea, with confirmed elevated serum prolactin. This picture is highly suspicious for a pituitary prolactinoma.

• A (Incorrect): CT scan provides less detailed imaging of the pituitary compared to MRI.
• B (Correct): MRI scan of the head (specifically focusing on the pituitary gland with contrast) is the gold standard investigation to visualize the pituitary, confirm the presence and size of an adenoma, and assess its relationship to surrounding structures.
• C (Incorrect): Cytological examination of nipple discharge is generally not helpful unless blood is present or infection is suspected; it doesn’t diagnose the cause of hyperprolactinemia.
• D (Incorrect): Thyroid function tests should ideally be checked as part of the hyperprolactinemia workup (as hypothyroidism can elevate prolactin), but imaging is now the priority given the confirmed high prolactin and symptoms.
• E (Incorrect): X-ray of the pituitary fossa is outdated and insensitive compared to MRI.

References:

• NICE CKS: Hyperprolactinaemia (Last revised Sep 2023)

Explanation: The combination of primary amenorrhea, normal breast development (indicating estrogen presence), absent axillary/pubic hair (indicating lack of androgen action), and absent uterus on ultrasound strongly suggests Androgen Insensitivity Syndrome (AIS).

• A (Incorrect): CT brain is irrelevant.
• B (Correct): Karyotyping is the definitive investigation. It will reveal a 46,XY genotype, confirming the diagnosis of AIS in this phenotypic female. Measurement of Serum FSH level is less critical for the primary diagnosis here, though it might be done as part of a broader workup.
• C (Incorrect): Serum Estrogen level will be in the normal female range (or even high) due to aromatization of testosterone, consistent with breast development, but doesn’t give the diagnosis.
• D (Incorrect): Serum Testosterone level will be in the normal or high *male* range, as the testes are producing testosterone, but the tissues cannot respond. While informative, karyotype is the definitive diagnostic test.

Note: Option B includes both Serum FSH level and Karyotype. Karyotype is the most crucial part.

Explanation: The presentation of vaginal bleeding along with secondary sexual characteristics (like breast development or pubic hair) in a 7-year-old girl constitutes precocious puberty (puberty onset before age 8 in girls). Investigation aims to determine the cause (central vs. peripheral).

• A (Correct): Abdominal and pelvic Ultrasound Scan (USS) is a crucial initial investigation. It assesses ovarian size and morphology (e.g., presence of cysts or tumours), uterine size, and endometrial thickness, helping to differentiate between causes and rule out ovarian tumours causing peripheral precocious puberty.
• B (Incorrect): Serum GnRH levels themselves are less useful than a GnRH stimulation test, which helps differentiate central (gonadotropin-dependent) from peripheral (gonadotropin-independent) precocious puberty, usually performed after initial assessment.
• C (Incorrect): Estradiol levels will likely be elevated, confirming estrogen exposure, but USS is more informative initially for anatomical assessment.
• D (Incorrect): Prolactin is not typically indicated unless galactorrhea is present or a pituitary lesion is suspected.
• E (Incorrect): Pregnancy is extremely unlikely and not the primary consideration.

Explanation: Premature Ovarian Insufficiency (POI) can be caused by factors that damage the ovaries or deplete the follicular pool prematurely.

• A (Correct): Chemotherapy, particularly alkylating agents, is gonadotoxic and a well-known cause of POI.
• B (Correct): Pelvic radiotherapy can damage the ovaries, leading to POI. The risk depends on the dose and field of radiation.
• C (Correct): Turner syndrome (45,X and variants) involves gonadal dysgenesis, typically leading to primary ovarian failure (presenting as primary amenorrhea or POI).
• D (Correct): Carriers of the Fragile X premutation (FMR1 gene) have an increased risk of developing POI.
• E (Incorrect): Advice on breastfeeding is unrelated to the risk of developing POI.

Note: The options provided in the user’s text for ‘2017 May Q18’ were incorrect (related to jaundice). These correct options are sourced from ‘2015 November Q18’ and the user’s sample CSV (ID 340), assuming this is the intended question content.

References:

• NICE NG23: Menopause: diagnosis and management (Published Nov 2015, last updated Dec 2019)

Explanation: Hormonal characteristics of PCOS:

• A (Correct): Testosterone levels (total or free) are often elevated, contributing to clinical hyperandrogenism (hirsutism, acne). Biochemical hyperandrogenism is one of the Rotterdam diagnostic criteria.
• B (Incorrect): Basal insulin levels are often elevated due to underlying insulin resistance.
• C (Incorrect): Serum estrogen levels (specifically estradiol) are typically normal or mildly elevated due to peripheral conversion of androgens and chronic follicular activity, not low.
• D (Correct): Luteinizing hormone (LH) levels are frequently elevated, often with an increased LH:FSH ratio, although this is not a mandatory diagnostic criterion.
• E (Incorrect): Sex hormone binding globulin (SHBG) levels are typically decreased, leading to a higher proportion of free, biologically active androgens and estrogens.

References:

• NICE Guideline NG89: Polycystic ovary syndrome: investigation and management (Published Sep 2018)

Explanation:

• A (Correct): Primary amenorrhea is defined as the absence of menstruation by age 15 years in the presence of normal growth and secondary sexual characteristics, or by age 13 years if there is no evidence of pubertal development (NICE CKS). Age 16 was an older definition but is still clinically relevant in context.
• B (Correct): Karyotyping is a crucial first-line investigation, especially if there are signs suggestive of Turner syndrome (e.g., short stature, webbed neck) or if gonadotropins are high (NICE CKS).
• C (Incorrect): The presence of secondary sexual characteristics does not exclude an XY genotype. For example, in Androgen Insensitivity Syndrome (AIS), individuals are genetically male (XY) but develop female secondary sexual characteristics due to androgen receptor defects.
• D (Correct): Anatomical abnormalities like a transverse vaginal septum or imperforate hymen obstruct menstrual outflow and are causes of primary amenorrhea, often presenting with cyclical pain.
• E (Correct): Conditions like malnutrition, chronic illness, or excessive exercise can cause hypothalamic dysfunction leading to delayed puberty and primary amenorrhea.

References:

• NICE CKS: Amenorrhoea (Last revised Nov 2022)

Explanation: Similar to Q25 (2016 Nov), this presentation points towards an anatomical obstruction of menstrual outflow in a girl with normal pubertal development.

• A (Correct): Abdominal-pelvic Ultrasound Scan (USS) is the most useful initial investigation to visualize the pelvic organs, confirm the presence of a uterus, and identify potential obstructions like imperforate hymen or transverse vaginal septum, often showing hematocolpos/hematometra.
• B (Incorrect): Buccal smear for Barr bodies is an outdated method for karyotyping; direct karyotyping is preferred if chromosomal abnormality is suspected (less likely here given normal development).
• C (Incorrect): Serum FSH level is expected to be normal and less helpful than imaging.
• D (Incorrect): Serum thyroxin level is irrelevant unless thyroid dysfunction is suspected as a cause of menstrual disturbance (unlikely primary amenorrhea cause here).
• E (Incorrect): X-ray of the wrist assesses bone age, not relevant for outflow obstruction.

Explanation: Delayed menstruation (primary amenorrhea if meets age criteria, or delayed menarche) with cyclical pain and normal secondary sexual characteristics points strongly to an outflow tract obstruction.

• A (Incorrect): Ovarian resistant syndrome (Savage syndrome) involves high gonadotropins but lack of ovarian response, usually presenting with primary amenorrhea and lack of breast development.
• B (Correct): A Transverse vaginal septum is a congenital anomaly obstructing the vagina. Menstrual blood accumulates above the septum (hematocolpos/hematometra), causing cyclical pain, while normal ovarian function allows for normal breast development.
• C (Incorrect): Testicular feminization (Androgen Insensitivity Syndrome) involves absent uterus and typically absent/sparse pubic hair, though breast development is normal.
• D (Incorrect): Constitutional delay involves delayed onset of puberty overall (both breast development and menarche).
• E (Incorrect): Turner syndrome typically presents with short stature and absent/delayed breast development due to ovarian failure.

Explanation: The combination of menstrual irregularity (oligomenorrhea), galactorrhea (nipple discharge), and headaches strongly suggests hyperprolactinemia, potentially caused by a pituitary adenoma (prolactinoma).

• A (Incorrect): MRI brain is indicated if serum prolactin is significantly elevated, but it’s not the initial investigation.
• B (Incorrect): Serum FSH/LH are part of the amenorrhea workup but are less specific for this presentation than prolactin.
• C (Correct): Measuring serum prolactin is the most appropriate initial investigation to confirm or exclude hyperprolactinemia. NICE CKS recommends checking prolactin in women with galactorrhea or oligomenorrhea/amenorrhea.
• D (Incorrect): Thyroid tests (TSH) are important because hypothyroidism can cause mild hyperprolactinemia, but prolactin measurement is more direct.
• E (Incorrect): X-ray of the pituitary fossa is outdated and lacks the sensitivity of MRI.

References:

• NICE CKS: Amenorrhoea (Last revised Nov 2022)
• NICE CKS: Hyperprolactinaemia (Last revised Sep 2023)

Explanation: This presentation – primary amenorrhea with normal secondary sexual development (indicating normal ovarian estrogen production) and cyclical lower abdominal pain – strongly suggests an outflow tract obstruction preventing menstruation.

• A (Incorrect): Full blood count is irrelevant unless severe anemia from concealed bleeding is suspected, which is unlikely.
• B (Incorrect): Laparoscopy is an invasive surgical procedure, not a first-line investigation for this presentation.
• C (Incorrect): Serum FSH and LH levels are likely to be normal, consistent with normal ovarian function, and less helpful than imaging in this context.
• D (Correct): An ultrasound scan of the abdomen and pelvis is the most appropriate initial investigation. It can visualize the uterus and detect hematocolpos (accumulation of blood in the vagina) or hematometra (blood in the uterus) caused by obstructions like an imperforate hymen or transverse vaginal septum. It also confirms the presence of the uterus (ruling out Mullerian agenesis).
• E (Incorrect): X-ray of the left wrist assesses bone age, relevant for delayed puberty but not for suspected outflow tract obstruction with normal development.

Explanation: Primary amenorrhea with normal secondary sexual characteristics and cyclical lower abdominal pain strongly suggests an obstruction to menstrual outflow.

• A (Incorrect): Constitutional delay involves delay in both menarche and secondary sexual development.
• B (Correct): Imperforate hymen is a classic cause of this presentation. Normal ovarian function leads to estrogen production and secondary sexual development. Menstrual blood is produced but cannot exit, accumulating in the vagina (hematocolpos) and causing cyclical pain.
• C (Incorrect): Mullerian agenesis involves absence of the uterus, so there would be no cyclical pain from trapped menses (though cyclical ovarian pain is possible but less typical).
• D (Incorrect): Polycystic ovarian syndrome typically presents later or with irregular cycles after menarche, not usually primary amenorrhea with cyclical pain.
• E (Incorrect): ‘Testicular artery’ is not a diagnosis. Testicular feminization (AIS) involves absent uterus.

Note: Question text is incomplete (with ………”). Assuming the missing part describes the cyclical nature of the pain.

“

Explanation:

• A (Correct): Secondary amenorrhea is commonly defined as the absence of menstruation for 3 months in women with previously regular cycles or 6 months in women with previously irregular cycles (NICE CKS). Therefore, 6 months is a valid criterion.
• B (Correct): The first step in investigating secondary amenorrhea is always to exclude pregnancy with a beta hCG test.
• C (Correct): Functional hypothalamic amenorrhea, often linked to stress, weight loss, or excessive exercise (including eating disorders), is a common cause. A thorough history is crucial (NICE CKS).
• D (Incorrect): Mullerian agenesis (absence of uterus and upper vagina) is a cause of primary amenorrhea.
• E (Incorrect): Premature ovarian insufficiency (POI) is characterized by high FSH levels (typically >25 IU/L on two occasions >4 weeks apart), not low FSH levels (NICE Guideline NG23).

References:

• NICE CKS: Amenorrhoea (Last revised Nov 2022)
• NICE NG23: Menopause: diagnosis and management (Published Nov 2015, last updated Dec 2019)

Explanation:

• A (Incorrect): PCOS is a major risk factor for endometrial cancer due to chronic anovulation and unopposed estrogen, but it is not directly linked to causing ovarian cancer.
• B (Incorrect): Hirsutism in PCOS can be managed and improved with treatments (e.g., COCPs, anti-androgens, cosmetic measures), although it may require long-term management. It’s not necessarily irreversible.
• C (Incorrect): Obesity is strongly associated with PCOS and exacerbates its features, but it is not one of the formal Rotterdam diagnostic criteria (which are: oligo/anovulation, clinical/biochemical hyperandrogenism, polycystic ovaries on ultrasound – need 2 out of 3).
• D (Correct): Peripheral insulin resistance and subsequent hyperinsulinemia are key pathophysiological features in a majority of women with PCOS, contributing to both hyperandrogenism and metabolic risks.
• E (Incorrect): PCOS is typically characterized by elevated LH levels and normal or low FSH levels. An increase in FSH is not required for diagnosis; high FSH suggests ovarian failure.

References:

• NICE Guideline NG89: Polycystic ovary syndrome: investigation and management (Published Sep 2018)

Explanation: This woman has amenorrhea and polycystic ovarian morphology on USS, suggesting PCOS, although hormone levels are reported as normal (interpretation can depend on reference ranges and specific hormones tested). As she is unmarried, fertility is not the immediate goal. The primary aims are usually cycle regulation, management of metabolic risks, and addressing symptoms like hirsutism if present.

• A (Incorrect): Ovarian drilling is a surgical option typically reserved for infertility management in clomiphene-resistant PCOS.
• B (Incorrect): Inducing a withdrawal bleed with progestogens confirms estrogen presence but doesn’t address the underlying anovulation or metabolic issues long-term.
• C (Incorrect): Clomiphene citrate is used for ovulation induction in women desiring pregnancy.
• D (Incorrect): Metformin is primarily used for managing insulin resistance and improving metabolic profile in PCOS, and sometimes for ovulation induction, but lifestyle changes are usually prioritized first, especially if hormones are ‘normal’.
• E (Correct): Lifestyle modification, including weight reduction if overweight or obese, is the cornerstone of PCOS management according to NICE guidelines. It can improve menstrual regularity, metabolic parameters, and reduce long-term health risks, even with ‘normal’ hormones.

References:

• NICE Guideline NG89: Polycystic ovary syndrome: investigation and management (Published Sep 2018)

Explanation: This presentation is nearly identical to the previous question (2014 May Q34) and highly characteristic of Androgen Insensitivity Syndrome (AIS): primary amenorrhea, normal height, normal female secondary sexual characteristics (breast development implies estrogen), but absent pubic/axillary hair (implies lack of androgen effect), short/blind vagina, and absent uterus.

• A (Incorrect): Checking buccal Barr bodies is an outdated method for determining sex chromosomes.
• B (Incorrect): Diagnostic laparoscopy might confirm absent Mullerian structures and locate testes but is invasive and not the primary diagnostic step.
• C (Incorrect): FSH & LH levels might be normal or slightly elevated but are not diagnostic of AIS itself.
• D (Correct): Karyotyping is the essential investigation to confirm the 46,XY genotype, establishing the diagnosis of AIS.

Explanation: This woman presents with secondary amenorrhea (unusual with regular cycles prior, needs clarification, but main issue is infertility + endometrioma), infertility, and a significant endometrioma (5cm). Management should address both the endometrioma and assess fertility factors.

• A (Incorrect): Aspiration of endometriomas has a very high recurrence rate and is generally not recommended as definitive treatment.
• B (Correct): Laparoscopic cystectomy (surgical removal of the endometrioma wall) is the preferred surgical approach for endometriomas >3-4cm, especially in the context of infertility, as it may improve spontaneous conception rates or response to ART (Assisted Reproductive Technology). Performing a dye test (chromopertubation) during the laparoscopy assesses tubal patency, which is crucial for fertility assessment. RCOG guidelines support surgical management for larger endometriomas associated with pain or infertility.
• C (Incorrect): Combined Oral Contraceptive Pills (COCP) can manage symptoms but suppress ovulation and are contraindicated when trying to conceive.
• D, E (Incorrect): Options missing.

References:

• RCOG Green-top Guideline No. 24: The Investigation and Management of Endometriosis (Published Sep 2022)
• ESHRE Guideline: Endometriosis (Published 2022)

Explanation: Premature Ovarian Insufficiency (POI) refers to the loss of ovarian function before the age of 40. Known causes include:

• A (Correct): Autoimmune disorders (e.g., Addison’s disease, thyroid disease) can target the ovaries, leading to POI. Autoimmune oophoritis is a recognised cause.
• B (Correct): Chromosomal abnormalities, most notably Turner syndrome (45,X and variants) and Fragile X premutation (FMR1 gene), are significant genetic causes.
• C (Incorrect): Combined Oral Contraceptive Pills (COCPs) suppress ovarian function temporarily but do not cause permanent failure or POI.
• D (Incorrect): Multiparity (having borne multiple children) is not associated with an increased risk of POI.
• E (Correct): Mumps infection can, in rare cases, lead to oophoritis (inflammation of the ovaries), potentially causing ovarian damage and subsequent POI.

Other causes: iatrogenic (chemotherapy, radiotherapy, surgery), other genetic factors, idiopathic.

References:

• NICE NG23: Menopause: diagnosis and management (Published Nov 2015, last updated Dec 2019)

Explanation:

• A (Incorrect): Combined Oral Contraceptive Pills (OCPs) suppress gonadotropin release, leading to low FSH levels.
• B (Incorrect): While LH is typically elevated (often with an increased LH:FSH ratio) in PCOS, FSH levels are usually normal or low.
• C (Correct): Premature menopause (Premature Ovarian Insufficiency, POI) is characterized by ovarian follicle depletion, leading to reduced estrogen production and loss of negative feedback, resulting in elevated FSH levels (NICE NG23).
• D (Incorrect): Sheehan’s syndrome (postpartum pituitary necrosis) causes hypopituitarism, leading to low or inappropriately normal FSH levels.
• E (Correct): Turner’s syndrome (45,X or variants) involves gonadal dysgenesis, resulting in primary ovarian failure and consequently high FSH levels due to lack of negative feedback.

References:

• NICE NG23: Menopause: diagnosis and management (Published Nov 2015, last updated Dec 2019)

Explanation: The rapid onset (6 months) of significant hirsutism accompanied by virilization (clitoromegaly) and acne in a 19-year-old strongly suggests a source of excessive androgen production, such as an androgen-secreting ovarian or adrenal tumour, or severe PCOS/congenital adrenal hyperplasia.

• A (Incorrect): Blood glucose is relevant for assessing metabolic aspects of PCOS but not the primary investigation for virilization.
• B (Incorrect): MRI pituitary is for suspected pituitary causes (like Cushing’s disease or prolactinoma), not the first step for peripheral signs of androgen excess.
• C (Correct): Measuring serum androgen levels, particularly total testosterone and possibly DHEAS (to help differentiate ovarian vs. adrenal source), is the most crucial initial investigation to quantify the degree of hyperandrogenism and guide further steps. Very high levels are highly suspicious for a tumour.
• D (Incorrect): Steroid binding globulin (SHBG) will likely be low, contributing to higher free androgen levels, but measuring the androgens themselves is the priority.
• E (Incorrect): USS abdomen/pelvis is important to look for ovarian or adrenal masses but should typically follow hormonal assessment confirming significant hyperandrogenism, unless clinical suspicion for tumour is extremely high.

Explanation: This clinical triad (amenorrhea, galactorrhea, headaches) is highly suggestive of hyperprolactinemia, likely due to a pituitary adenoma.

• A (Incorrect): MRI of the pituitary is indicated if serum prolactin is confirmed to be significantly elevated, but it’s not the first step after the negative pregnancy test.
• B (Correct): Checking the serum prolactin level is the essential next step to confirm the suspected hyperprolactinemia. NICE CKS guidelines recommend this as an initial investigation for amenorrhea and galactorrhea.
• C (Incorrect): Visual perimetry (visual field testing) is done if a large pituitary tumor (macroadenoma) is suspected or confirmed, to check for optic chiasm compression, but it follows prolactin testing and usually imaging.
• D (Incorrect): Checking FSH/LH levels is part of the general amenorrhea workup but less specific for this presentation than prolactin.
• E (Incorrect): Checking progesterone levels assesses ovulation, which is relevant for amenorrhea but doesn’t directly address the likely cause suggested by galactorrhea and headaches.

References:

• NICE CKS: Amenorrhoea (Last revised Nov 2022)
• NICE CKS: Hyperprolactinaemia (Last revised Sep 2023)

Explanation: A significantly elevated serum prolactin level (hyperprolactinemia) in the context of secondary amenorrhea warrants investigation for a pituitary cause, most commonly a prolactinoma.

• A (Incorrect): Bromocriptine (a dopamine agonist) is a treatment for hyperprolactinemia, but diagnosis should precede treatment.
• B (Correct): MRI of the pituitary gland is the imaging modality of choice to visualize the pituitary, identify adenomas, and assess their size and relationship to surrounding structures (e.g., optic chiasm). NICE guidelines recommend pituitary imaging if prolactin levels are significantly elevated.
• C (Incorrect): While checking TSH is important in the workup of hyperprolactinemia (as hypothyroidism can cause mildly elevated prolactin), with a level of 500 IU/L, imaging the pituitary is the priority.
• D (Incorrect): Checking visual fields is necessary if a large pituitary tumor (macroadenoma) potentially compressing the optic chiasm is suspected or found on MRI, but it’s not the initial step after the blood test.
• E (Incorrect): X-ray of the pituitary fossa is an outdated and less sensitive method compared to MRI for evaluating pituitary pathology.

References:

• NICE CKS: Amenorrhoea (Last revised Nov 2022)
• NICE CKS: Hyperprolactinaemia (Last revised Sep 2023)

Explanation: The Hypothalamic-Pituitary-Ovarian (HPO) axis regulates the menstrual cycle through hormonal feedback.

• A (Correct): GnRH analogues (agonists and antagonists) directly act on the pituitary gland, initially stimulating then suppressing (agonists after downregulation) or directly blocking (antagonists) gonadotropin release, thus profoundly influencing the HPO axis.
• B (Incorrect): Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) used for pain relief (dysmenorrhea) and reducing heavy menstrual bleeding by inhibiting prostaglandin synthesis; it does not directly act on the HPO axis hormones.
• C (Incorrect): Tranexamic acid is an antifibrinolytic agent used to reduce heavy menstrual bleeding; it does not act on the HPO axis.
• D (Correct): Nutrition significantly influences the HPO axis. Severe undereating, malnutrition, or excessive exercise can suppress GnRH pulsatility, leading to functional hypothalamic amenorrhea. Body composition (adipose tissue) also plays a role via hormones like leptin.
• E (Correct): Thyroid hormones influence the HPO axis. Both hypothyroidism and hyperthyroidism can disrupt GnRH pulsatility and ovarian function, leading to menstrual irregularities. Thyroid hormones also affect prolactin levels.

Explanation: Polycystic Ovarian Syndrome (PCOS) is associated with several long-term health risks, primarily due to chronic anovulation, insulin resistance, and hyperandrogenism.

• A (Incorrect): PCOS is generally associated with normal or even increased bone density due to higher estrogen and androgen levels; it is not a risk factor for osteoporosis.
• B (Correct): Chronic anovulation leads to prolonged exposure of the endometrium to unopposed estrogen (relative progesterone deficiency), significantly increasing the risk of endometrial hyperplasia and endometrial cancer (NICE NG89).
• C (Correct): Insulin resistance is a core feature of PCOS, markedly increasing the risk of developing impaired glucose tolerance and Type 2 Diabetes Mellitus (NICE NG89).
• D (Correct): Women with PCOS experience higher rates of miscarriage, although the exact mechanisms are complex and may involve hormonal imbalances, uterine environment factors, and metabolic dysfunction.
• E (Correct): PCOS is associated with an increased risk of cardiovascular risk factors, including dyslipidemia, hypertension, and potentially ischemic heart disease, linked to insulin resistance and chronic inflammation (NICE NG89).

References:

• NICE Guideline NG89: Polycystic ovary syndrome: investigation and management (Published Sep 2018)

Explanation: The rapid onset or worsening of hirsutism, particularly with signs of virilization (like clitoromegaly, voice deepening – although only mild virilization noted here) in a woman with PCOS, raises suspicion for an androgen-secreting tumour, either ovarian or adrenal. The identification of an adrenal mass on USS points towards an adrenal source.

• A (Correct): Measuring adrenal androgens, such as Androstenedione and DHEAS (Dehydroepiandrosterone sulfate – primarily adrenal), is crucial. Testosterone should also be measured. Very high levels suggest a tumour.
• B (Incorrect): MRI of the abdomen might be used for better characterization of the adrenal mass identified on USS, but hormonal assessment is the next logical step to determine if the mass is functional (secreting androgens).
• C (Incorrect): CT brain is irrelevant unless pituitary pathology is suspected, which is not the primary concern here.
• D (Incorrect): Urine VMA (Vanillylmandelic acid) is used to investigate pheochromocytoma (an adrenaline-secreting adrenal tumour), not typically androgen-secreting tumours.
• E (Incorrect): Option missing, but hormonal assessment is key.

Note: Although the question number is 39 (suggesting checkbox), the phrasing ‘What should be the next investigation?’ strongly implies a single best answer. However, adhering strictly to the rule Q<40=checkbox, this is marked as checkbox. Measuring multiple androgens could be considered correct. *User feedback required if intended as SBA.* Assuming checkbox based on number.

Explanation: The clinical features described – primary amenorrhea, short stature (120cm is significantly short for an 18-year-old), neck webbing, and minimal secondary sexual characteristics (indicating lack of estrogen, i.e., ovarian failure) – are classic signs of Turner syndrome.

• A (Incorrect): Abdominal USS might show streak ovaries and assess the uterus, but it doesn’t provide the definitive genetic diagnosis.
• B (Incorrect): Diagnostic laparoscopy is an invasive procedure and not indicated as a first-line investigation for suspected Turner syndrome.
• C (Incorrect): LH and FSH levels would be expected to be high (hypergonadotropic hypogonadism) due to ovarian failure, confirming the hypogonadism but not the underlying cause.
• D (Correct): Karyotyping is essential to confirm the diagnosis of Turner syndrome by identifying the characteristic chromosomal abnormality (e.g., 45,X or mosaicism). NICE CKS recommends karyotyping in primary amenorrhea, especially with associated features.
• E (Incorrect): Serum prolactin levels are not typically relevant in the investigation of suspected Turner syndrome.

References:

• NICE CKS: Amenorrhoea (Last revised Nov 2022)

Explanation: For an unmarried woman with PCOS not currently seeking fertility, management focuses on managing symptoms (like irregular cycles, hirsutism) and reducing long-term metabolic and cardiovascular risks. NICE guidelines emphasize lifestyle changes as first-line.

• A (Correct): Weight loss (if overweight/obese) and lifestyle modification (diet, exercise) are considered the most beneficial first-line treatments. They can improve insulin sensitivity, restore ovulation, regulate cycles, and reduce long-term health risks associated with PCOS.
• B (Correct): The Combined Oral Contraceptive Pill (COCP) is also a first-line option, particularly for cycle regulation and managing hyperandrogenic symptoms (hirsutism, acne). It does not address the underlying insulin resistance but manages key symptoms effectively. The ‘most’ beneficial depends on the primary concern (metabolic vs. symptoms) and patient preference, but lifestyle is often emphasized first. *Since both A and B are strong contenders and considered first-line depending on context, and this is SBA, lifestyle (A) is often cited as the foundational management impacting long-term health most broadly.* However, COCP (B) directly addresses common distressing symptoms. Given the options, both A and B could be argued as highly beneficial. Let’s check NICE guidelines for emphasis. NICE NG89 suggests lifestyle first, then pharmacological options like COCP or metformin depending on need. Thus, A might be slightly preferred as the foundational step. *Revising based on the user’s prior CSV having dual correct answers for a similar question (ID 338) – acknowledging both as potentially beneficial but selecting one as ‘most’ per SBA format.* Let’s stick with Weight loss as the primary foundational recommendation.
• C (Incorrect): Metformin is used for managing insulin resistance/impaired glucose tolerance or sometimes as second-line for ovulation induction, not typically first-line for general PCOS management unless specific indications exist.
• D (Incorrect): Omega 3 fish oil has insufficient evidence for primary PCOS management.
• E (Incorrect): Clomiphene citrate is for ovulation induction (fertility treatment).

Note: Marked as radio (Q46). Re-evaluating choice A vs B. NICE recommends discussing lifestyle AND pharmacological options (like COCP). Depending on BMI and symptoms, COCP might be chosen first for symptoms. If BMI is high, weight loss is paramount. Without BMI info, it’s tough. Given PCOS diagnosis implies potential metabolic issues, weight loss addresses this more directly. Let’s prioritize weight loss/lifestyle as ‘most beneficial’ foundationally.

References:

• NICE Guideline NG89: Polycystic ovary syndrome: investigation and management (Published Sep 2018)