A 15-year-old girl child with primary amenorrhea has pubic hair, prepubertal breast, blind vagina, clitoromegaly, and normal testosterone. Karyotype given is 46 XY , what is the cause?
Q312
A 19-year-old woman presents with irregular menstrual cycles for the past 3 years and facial acne. Patient says she had menarche at the age of 11, established a regular cycle at 13, and had regular menses until the age of 16. Patient is sexually active with a single partner, and they use barrier contraception. They currently do not plan to get pregnant. There is no significant past medical history and she takes no current medications. Vitals are temperature 37.0℃ (98.6℉), blood pressure 125/85 mm Hg, pulse 69/min, respiratory rate 14/min, and oxygen saturation 99% on room air. Physical examination is significant for multiple comedones on her face. She also has hair on her upper lip, between her breasts, along with the abdominal midline, and on her forearms. There is hyperpigmentation of the axillary folds and near the nape of the neck. Laboratory tests are significant for the following:
Sodium 141 mEq/L
Potassium 4.1 mEq/L
Chloride 101 mEq/L
Bicarbonate 25 mEq/L
BUN 12 mg/dL
Creatinine 1.0 mg/dL
Glucose (fasting) 131 mg/dL
Bilirubin, conjugated 0.2 mg/dL
Bilirubin, total 1.0 mg/dL
AST (SGOT) 11 U/L
ALT (SGPT) 12 U/L
Alkaline Phosphatase 45 U/L
WBC 6,500/mm3
RBC 4.80 x 106/mm3
Hematocrit 40.5%
Hemoglobin 14.0 g/dL
Platelet Count 215,000/mm3
TSH 4.4 μU/mL
FSH 73 mIU/mL
LH 210 mIU/mL
Testosterone, total 129 ng/dL (ref: 6-86 ng/dL)
β-hCG 1 mIU/mL
Which of the following is the best course of treatment for this patient?
Q313
Which cancer is most commonly associated with increased estrogen levels?
Q314
The menstrual cycle can be best assessed by:
Q315
A 16-year-old girl comes to you with primary amenorrhea; on evaluation there is absent breast development, she has a normal stature, her FSH and LH levels are found to be high and she has a karyotype of 46XX. What is the probable diagnosis?
Q316
A 28-year-old woman with a history of PCOS presents with amenorrhea. What is the most likely cause of her amenorrhea?
Q317
A 15-year-old girl presents with weight gain, irregular menses, and hirsutism. Laboratory results show increased testosterone, an elevated LH/FSH ratio, and normal prolactin levels. Evaluate and determine the most effective long-term management.
Q318
A 25-year-old woman presents with primary infertility and hirsutism. Laboratory results show elevated testosterone and an increased LH/FSH ratio. What is the diagnosis?
Q319
In which phase of the menstrual cycle does the corpus luteum develop and secrete progesterone to prepare the endometrium for potential implantation?
Q320
A 26-year-old woman presents with primary amenorrhea, normal secondary sexual characteristics, and an absent uterus on ultrasound. What is the most likely diagnosis?
Reproductive Endocrinology Indian Medical PG Practice Questions and MCQs
Question 311: A 15-year-old girl child with primary amenorrhea has pubic hair, prepubertal breast, blind vagina, clitoromegaly, and normal testosterone. Karyotype given is 46 XY , what is the cause?
A. 17 hydroxylase deficiency
B. 5-alpha reductase deficiency (Correct Answer)
C. Swyer syndrome
D. Complete AIS
Explanation: ***5-alpha reductase deficiency***
- The presence of **primary amenorrhea**, **pubic hair**, **clitoromegaly**, **blind vagina**, and a **46 XY karyotype** with **normal testosterone** levels points to 5-alpha reductase deficiency. In this condition, the body cannot convert testosterone to the more potent dihydrotestosterone (DHT) needed for external male genitalia development in utero.
- Individuals with this condition are typically raised as girls, but at puberty, they develop **virilization** (e.g., clitoromegaly, deepening voice, pubic hair) due to an increase in testosterone, which can still exert some androgenic effects.
*17 hydroxylase deficiency*
- This deficiency affects both adrenal and gonadal steroid synthesis, leading to **hypertension**, **hypokalemia**, and **primary amenorrhea** in 46 XY individuals.
- It would also result in **low testosterone levels**, which contradicts the normal testosterone mentioned in the case.
*Swyer syndrome*
- Swyer syndrome (46 XY pure gonadal dysgenesis) is characterized by a **46 XY karyotype** but rudimentary or streak gonads, leading to **primary amenorrhea** and an **absence of secondary sexual characteristics** (no breast development, no pubic hair).
- These individuals have **low testosterone** and high gonadotropins, and they present with a **female phenotype** and a **uterus**, which contradicts the features of pubic hair and clitoromegaly.
*Complete AIS*
- Complete Androgen Insensitivity Syndrome (CAIS) also presents with a **46 XY karyotype**, **primary amenorrhea**, and a **blind vagina**.
- However, individuals with CAIS have **undescended testes** that produce testosterone, but their cells cannot respond to it due to defective androgen receptors, resulting in **breast development** at puberty (due to peripheral conversion of testosterone to estrogen) and **absent or sparse pubic/axillary hair** (since androgen receptors are non-functional).
- The presence of **pubic hair** and **clitoromegaly** in this case rules out CAIS.
Question 312: A 19-year-old woman presents with irregular menstrual cycles for the past 3 years and facial acne. Patient says she had menarche at the age of 11, established a regular cycle at 13, and had regular menses until the age of 16. Patient is sexually active with a single partner, and they use barrier contraception. They currently do not plan to get pregnant. There is no significant past medical history and she takes no current medications. Vitals are temperature 37.0℃ (98.6℉), blood pressure 125/85 mm Hg, pulse 69/min, respiratory rate 14/min, and oxygen saturation 99% on room air. Physical examination is significant for multiple comedones on her face. She also has hair on her upper lip, between her breasts, along with the abdominal midline, and on her forearms. There is hyperpigmentation of the axillary folds and near the nape of the neck. Laboratory tests are significant for the following:
Sodium 141 mEq/L
Potassium 4.1 mEq/L
Chloride 101 mEq/L
Bicarbonate 25 mEq/L
BUN 12 mg/dL
Creatinine 1.0 mg/dL
Glucose (fasting) 131 mg/dL
Bilirubin, conjugated 0.2 mg/dL
Bilirubin, total 1.0 mg/dL
AST (SGOT) 11 U/L
ALT (SGPT) 12 U/L
Alkaline Phosphatase 45 U/L
WBC 6,500/mm3
RBC 4.80 x 106/mm3
Hematocrit 40.5%
Hemoglobin 14.0 g/dL
Platelet Count 215,000/mm3
TSH 4.4 μU/mL
FSH 73 mIU/mL
LH 210 mIU/mL
Testosterone, total 129 ng/dL (ref: 6-86 ng/dL)
β-hCG 1 mIU/mL
Which of the following is the best course of treatment for this patient?
A. Goserelin
B. Clomiphene
C. Finasteride
D. Oral contraceptives (Correct Answer)
Explanation: ***Oral contraceptives***
- The patient's presentation with **irregular menses**, **hirsutism** (facial, periareolar, abdominal, forearm hair), **acne**, **acanthosis nigricans** (hyperpigmentation in axillary folds and nape of neck), and **elevated fasting glucose** suggests **Polycystic Ovary Syndrome (PCOS)** [1]. The **elevated LH to FSH ratio** and **elevated testosterone** further support this diagnosis [3].
- **Oral contraceptives** are the **first-line treatment** for managing the symptoms of PCOS in women who do not desire immediate pregnancy, as they help regulate menstrual cycles, reduce androgen levels, and improve acne and hirsutism [2].
*Goserelin*
- **Goserelin** is a **GnRH agonist** that initially stimulates and then down-regulates gonadotropin release, leading to a **hypogonadal state**. It is used in conditions like **endometriosis**, **uterine fibroids**, or certain cancers.
- This medication is **not indicated** for the management of PCOS, especially given the patient's symptoms and goals.
*Clomiphene*
- **Clomiphene citrate** is an **estrogen receptor modulator** used to induce ovulation in anovulatory women who wish to conceive [4].
- The patient is **not attempting to conceive** and is using contraception, making clomiphene an inappropriate treatment at this time [4].
*Finasteride*
- **Finasteride** is a **5-alpha reductase inhibitor** that blocks the conversion of testosterone to its more potent form, dihydrotestosterone (DHT). It is primarily used to treat **androgenic alopecia** and **benign prostatic hyperplasia**.
- While it can reduce hirsutism, it **does not address the menstrual irregularities or metabolic aspects of PCOS** and is generally considered a second-line option for hirsutism, often in conjunction with oral contraceptives.
Question 313: Which cancer is most commonly associated with increased estrogen levels?
A. Ovarian
B. GTN
C. Breast (Correct Answer)
D. Cervix
Explanation: ***Breast***
- Many breast cancers, particularly **estrogen receptor-positive (ER+)** tumors, are fueled by **estrogen**.
- Prolonged exposure to high estrogen levels, such as early menarche, late menopause, or obesity, is a known risk factor for breast cancer.
*Ovarian*
- While estrogen does play a role in ovarian function, the link between **increased estrogen levels** and ovarian cancer risk, while present, is **less direct and less significant** than for breast cancer.
- Ovarian cancer is associated with other risk factors like **nulliparity**, **endometriosis**, and certain genetic mutations.
*GTN*
- **Gestational trophoblastic neoplasia (GTN)** is an abnormal proliferation of trophoblastic tissue, commonly occurring after pregnancy.
- Its development is primarily linked to **abnormal fertilization**, not directly to independently increased estrogen levels.
*Cervix*
- **Cervical cancer** is overwhelmingly caused by **persistent human papillomavirus (HPV) infection**.
- While hormonal factors can influence HPV progression, increased estrogen levels are **not considered a primary cause** or strongly associated risk factor for cervical cancer.
Question 314: The menstrual cycle can be best assessed by:
A. Fern test
B. Spinnbarkeit phenomenon
C. Sex steroid profile (Correct Answer)
D. Cytology of endometrium
Explanation: ***Sex steroid profile***
- A **sex steroid profile** directly measures the levels of key hormones like **estrogen** and **progesterone** throughout the cycle, providing the most comprehensive and accurate assessment of ovarian function and phases [2].
- Changes in these hormones dictate the events of the menstrual cycle, including ovulation and endometrial preparation [2].
*Fern test*
- The **fern test** assesses cervical mucus crystallization patterns, primarily indicating high estrogen levels, but it doesn't give a full picture of the entire cycle or progesterone influence [1].
- It's mainly used to confirm **rupture of membranes** in pregnancy or indicate the ovulatory phase [1].
*Spinnbarkeit phenomenon*
- **Spinnbarkeit phenomenon** refers to the stretchiness of cervical mucus, which primarily indicates high estrogen levels around ovulation [1].
- While useful for ovulation detection, it does not provide a comprehensive assessment of the entire female sexual cycle or hormonal fluctuations [2].
*Cytology of endometrium*
- **Endometrial cytology** involves examining cells from the uterine lining, which can show the effects of hormonal exposure but doesn't directly measure hormone levels or provide a dynamic assessment of the entire cycle [3].
- It is more commonly used to detect **abnormal cellular changes**, such as hyperplasia or malignancy.
Question 315: A 16-year-old girl comes to you with primary amenorrhea; on evaluation there is absent breast development, she has a normal stature, her FSH and LH levels are found to be high and she has a karyotype of 46XX. What is the probable diagnosis?
A. Testicular feminizing syndrome
B. Turner syndrome
C. Kallmann syndrome
D. Gonadal dysgenesis (Correct Answer)
Explanation: ***Gonadal dysgenesis***
- **Primary amenorrhea** with **absent breast development** and **high FSH/LH** (hypergonadotropic hypogonadism) in a **46,XX individual** with **normal stature** points to **46,XX gonadal dysgenesis** (pure gonadal dysgenesis).
- In this condition, the gonads fail to develop properly despite a normal female karyotype, leading to non-functional streak ovaries that fail to produce estrogen, hence the lack of secondary sexual characteristics and elevated gonadotropins due to lack of negative feedback.
- Unlike Turner syndrome, patients have normal stature and a normal 46,XX karyotype.
*Testicular feminizing syndrome*
- Individuals with **complete androgen insensitivity syndrome (CAIS)**, formerly called testicular feminizing syndrome, have a **46,XY karyotype** and develop external female characteristics due to complete androgen resistance.
- They present with **primary amenorrhea** but typically have **well-developed breasts** (from peripheral aromatization of testosterone to estrogen) and a blind-ending vagina, which contradicts the absent breast development in this case.
*Turner syndrome*
- Characterized by a **45,X karyotype** (or variants with mosaicism) and typically presents with **short stature**, primary amenorrhea, and gonadal dysgenesis.
- While it causes **primary amenorrhea** and **absent breast development** with high FSH/LH, the **normal stature** and **46,XX karyotype** in this patient rule out Turner syndrome.
*Kallmann syndrome*
- This condition is characterized by **hypogonadotropic hypogonadism** associated with **anosmia or hyposmia** due to defective GnRH secretion.
- Patients present with **low FSH and LH levels**, which contradicts the **high gonadotropin levels** seen in this case.
Question 316: A 28-year-old woman with a history of PCOS presents with amenorrhea. What is the most likely cause of her amenorrhea?
A. Anovulation (Correct Answer)
B. Hyperprolactinemia
C. Hypothyroidism
D. Premature ovarian failure
Explanation: ***Anovulation***
- **Polycystic Ovary Syndrome (PCOS)** is primarily characterized by **anovulation** or oligo-ovulation, leading directly to irregular menstrual cycles or amenorrhea due to a lack of regular follicle rupture and corpus luteum formation.
- The hormonal imbalances in PCOS, including elevated **androgens** and **insulin resistance**, disrupt the normal hypothalamic-pituitary-ovarian axis, preventing regular ovulation.
- This is the **most direct and common cause** of amenorrhea in patients with PCOS.
*Hyperprolactinemia*
- While hyperprolactinemia can cause **amenorrhea** by inhibiting **GnRH** pulsatility, it is not the most common or primary cause of amenorrhea in a patient specifically diagnosed with **PCOS**.
- Hyperprolactinemia would typically present with additional symptoms such as **galactorrhea**, which is not mentioned as a prominent feature of PCOS amenorrhea.
*Hypothyroidism*
- **Hypothyroidism** can cause menstrual irregularities, including **amenorrhea**, by affecting the metabolism of sex hormones and impacting the hypothalamic-pituitary-ovarian axis.
- However, hypothyroidism is a separate endocrine disorder and not the direct or most likely cause of amenorrhea in a patient already known to have **PCOS**, which has its own well-defined mechanism for menstrual dysfunction.
*Premature ovarian failure*
- **Premature ovarian failure (POF)** is characterized by the cessation of ovarian function before age 40, leading to elevated **FSH** and **LH** levels and amenorrhea.
- This condition is distinct from **PCOS**, where the ovaries are typically functional but anovulatory, and it would not be the expected cause of amenorrhea in a 28-year-old with a known history of PCOS.
Question 317: A 15-year-old girl presents with weight gain, irregular menses, and hirsutism. Laboratory results show increased testosterone, an elevated LH/FSH ratio, and normal prolactin levels. Evaluate and determine the most effective long-term management.
A. Oral contraceptives + lifestyle modification (Correct Answer)
B. Metformin + anti-androgens
C. Spironolactone + insulin sensitizers
D. GnRH analogs + surgical resection
Explanation: ***Oral contraceptives + lifestyle modification***
- **Oral contraceptives** are the cornerstone for managing **PCOS** symptoms like irregular menses and hirsutism by suppressing ovarian androgen production and providing continuous estrogen/progestin.
- **Lifestyle modifications**, including diet and exercise, address the associated **weight gain** and **insulin resistance**, improving overall hormonal balance and long-term health outcomes.
*Metformin + anti-androgens*
- **Metformin** primarily targets **insulin resistance** and may help with menstrual regularity and weight, but it does not directly manage hirsutism as effectively as oral contraceptives.
- **Anti-androgens** like spironolactone are effective for **hirsutism** but do not regulate menstrual cycles or provide contraception, making them less comprehensive as a sole long-term strategy.
*Spironolactone + insulin sensitizers*
- **Spironolactone** is an effective anti-androgen for **hirsutism**, but it can cause menstrual irregularities if not combined with hormonal contraception.
- While **insulin sensitizers** (like metformin) address a key physiological aspect of PCOS, they don't offer the comprehensive symptomatic relief (menstrual regulation, contraception) provided by oral contraceptives.
*GnRH analogs + surgical resection*
- **GnRH analogs** are typically reserved for severe, unresponsive cases due to their potential side effects and are not a first-line long-term management strategy for typical PCOS.
- **Surgical resection**, such as ovarian drilling, is rarely indicated for PCOS and is generally considered only for patients with infertility who do not respond to other treatments, not for routine long-term management of symptoms.
Question 318: A 25-year-old woman presents with primary infertility and hirsutism. Laboratory results show elevated testosterone and an increased LH/FSH ratio. What is the diagnosis?
A. Cushing's syndrome
B. PCOS (Correct Answer)
C. Hyperprolactinemia
D. Adrenal hyperplasia
Explanation: **Correct Option: PCOS**
- **Primary infertility**, **hirsutism**, **elevated testosterone**, and an **increased LH/FSH ratio** are classic diagnostic features of **polycystic ovary syndrome (PCOS)**.
- PCOS is an endocrine disorder characterized by **hormonal imbalances** that affect ovarian function and lead to ovulatory dysfunction and hyperandrogenism.
- The increased LH/FSH ratio (typically >2:1) is a characteristic finding that helps differentiate PCOS from other causes of hyperandrogenism.
*Incorrect: Cushing's syndrome*
- Cushing's syndrome is characterized by **excess cortisol** and typically presents with central obesity, moon facies, buffalo hump, and striae, which are not mentioned here.
- While it can cause hirsutism and menstrual irregularities, an elevated LH/FSH ratio and primary infertility specifically point away from Cushing's.
*Incorrect: Hyperprolactinemia*
- **Hyperprolactinemia** primarily causes **amenorrhea** or oligomenorrhea, **galactorrhea**, and infertility due to suppression of GnRH and gonadotropins.
- It does not typically present with elevated testosterone or an increased LH/FSH ratio.
*Incorrect: Adrenal hyperplasia*
- **Congenital adrenal hyperplasia (CAH)** can cause hirsutism and elevated androgens, but it usually presents in childhood with ambiguous genitalia or later with significant masculinization.
- While it can lead to high androgens, the specific combination of an elevated LH/FSH ratio and primary infertility is more indicative of PCOS.
Question 319: In which phase of the menstrual cycle does the corpus luteum develop and secrete progesterone to prepare the endometrium for potential implantation?
A. Menstrual phase
B. Follicular phase
C. Ovulatory phase
D. Luteal phase (Correct Answer)
Explanation: ***Luteal phase***
- Following **ovulation**, the ruptured follicle transforms into the **corpus luteum**, which is the hallmark of the luteal phase.
- The **corpus luteum** secretes high levels of **progesterone** (and some estrogen) to make the **endometrium receptive** for implantation.
*Menstrual phase*
- This phase involves the **shedding of the uterine lining** when pregnancy does not occur, characterized by low levels of both **estrogen** and **progesterone**.
- It marks the beginning of a new cycle, not the development of the **corpus luteum** or significant progesterone secretion.
*Follicular phase*
- During this phase, **follicles mature** under the influence of **FSH**, and **estrogen** levels rise, causing the **endometrium to proliferate**.
- The **corpus luteum** has not yet formed, and **progesterone levels** remain low.
*Ovulatory phase*
- This is a brief phase marked by the **surge in LH**, which triggers the **rupture of the mature follicle** and release of the egg.
- While it precedes the formation of the **corpus luteum**, the **corpus luteum** itself develops and becomes hormonally active *after* ovulation, during the luteal phase.
Question 320: A 26-year-old woman presents with primary amenorrhea, normal secondary sexual characteristics, and an absent uterus on ultrasound. What is the most likely diagnosis?
A. Turner syndrome
B. Androgen insensitivity syndrome
C. Mayer-Rokitansky-Küster-Hauser syndrome (Correct Answer)
D. Kallmann syndrome
Explanation: ***Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome***
- This syndrome is characterized by **congenital absence or hypoplasia of the uterus and upper two-thirds of the vagina** with **normal functioning ovaries**.
- Patients present with **primary amenorrhea** despite having **normal secondary sexual characteristics** (normal breast development, pubic/axillary hair) due to functional ovaries producing estrogen.
- **Normal 46,XX karyotype** with normal hormonal profile distinguishes this from other causes.
*Turner syndrome*
- Patients with Turner syndrome (45,XO karyotype) have **gonadal dysgenesis (streak gonads)** leading to **absent or poorly developed secondary sexual characteristics** due to lack of estrogen.
- They present with primary amenorrhea and short stature, but the **normal secondary sexual development** in this patient excludes Turner syndrome.
*Androgen insensitivity syndrome (AIS)*
- Complete AIS patients have **46,XY karyotype** but are phenotypically female with **normal breast development** (due to peripheral conversion of testosterone to estrogen).
- They have an **absent uterus and blind-ending vagina**, but typically present with **absent or sparse pubic/axillary hair** and have **undescended testes**.
- The complete female phenotype with normal pubic hair pattern makes MRKH more likely.
*Kallmann syndrome*
- This is a form of **hypogonadotropic hypogonadism** due to **GnRH deficiency**, associated with **anosmia or hyposmia**.
- Patients present with **delayed or absent puberty** and **poorly developed secondary sexual characteristics** due to low estrogen levels.
- The presence of **normal secondary sexual characteristics** in this patient excludes Kallmann syndrome.
