Fertilization begins when sperm binds to the corona radiata of the egg. Once the sperm enters the cytoplasm, a cortical reaction occurs which prevents other sperm from entering the oocyte. The oocyte then undergoes an important reaction. What is the next reaction that is necessary for fertilization to continue?

Formation of the spindle apparatus

A 58-year-old man comes to the physician for a 2-month history of increased urinary frequency. Urodynamic testing shows a urinary flow rate of 11 mL/s (N>15) and a postvoid residual volume of 65 mL (N<50). Prostate-specific antigen level is 3.2 ng/mL (N<4). Treatment with a drug that also increases scalp hair regrowth is initiated. Which of the following is the most likely mechanism of action of this drug?

Decreased conversion of testosterone to dihydrotestosterone

Gonadotropin-releasing hormone receptor agonism

Decreased conversion of hydroxyprogesterone to androstenedione

Decreased conversion of testosterone to estradiol

Selective alpha-1A/D receptor antagonism

A 76-year-old male presents to his primary care physician because he is concerned about changes in urination. Over the last few months, he has noticed increased urinary frequency as well as difficulty with initiating and stopping urination. He denies having pain with urination. Physical exam reveals a uniformly enlarged and non-tender prostate. Lab tests showed that the prostate specific antigen (PSA) was within normal limits. The patient did not tolerate an alpha blocker due to episodes of syncope so another medication is prescribed that affects testosterone metabolism. Which of the following disorders can also be treated with the medication most likely prescribed in this case?

Polycystic ovarian syndrome (PCOS)

A 70-year-old male presents to his primary care provider complaining of decreased sexual function. He reports that over the past several years, he has noted a gradual decline in his ability to sustain an erection. He used to wake up with erections but no longer does. His past medical history is notable for diabetes, hyperlipidemia, and a prior myocardial infarction. He takes metformin, glyburide, aspirin, and atorvastatin. He drinks 2-3 drinks per week and has a 25 pack-year smoking history. He has been happily married for 40 years. He retired from his job as a construction worker 5 years ago and has been enjoying retirement with his wife. His physician recommends starting a medication that is also used in the treatment of pulmonary hypertension. Which of the following is a downstream effect of this medication?

Decrease nitric oxide production

A 27-year-old woman comes to the physician for the evaluation of infertility. She has been unable to conceive for the past 2 years. Menses occur at 45 to 80-day intervals. She is 168 cm (5 ft 6 in) tall and weighs 77 kg (170 lb); BMI is 27.4 kg/m2. Physical examination shows facial acne and pigmented hair on the upper lip. Serum studies show elevated levels of testosterone and an LH:FSH ratio of 4:1. Treatment with the appropriate drug for this patient's infertility is begun. Which of the following is the primary mechanism of action of this drug?

Inhibition of hypothalamic estrogen receptors

Activation of pituitary dopamine receptors

Activation of granulosa cell aromatase

Activation of ovarian luteinizing hormone receptors

Inhibition of endometrial progesterone receptors

A 56-year-old man comes to the clinic complaining of sexual dysfunction. He reports normal sexual function until 4 months ago when his relationship with his wife became stressful due to a death in the family. When asked about the details of his dysfunction, he claims that he is “able to get it up, but just can’t finish the job.” He denies any decrease in libido or erections, endorses morning erections, but an inability to ejaculate. He is an avid cyclist and exercises regularly. His past medical history includes depression and diabetes, for which he takes citalopram and metformin, respectively. A physical examination is unremarkable. What is the most likely explanation for this patient’s symptoms?

Autonomic neuropathy secondary to systemic disease

Male sexual physiology for USMLE Step 3: High-Yield Physiology Lessons

Hormonal Axis - The Command Center

Pulsatile GnRH from the hypothalamus is the master switch.
Anterior Pituitary responds by releasing gonadotropins:
- LH (Luteinizing Hormone): Targets Leydig cells to produce Testosterone.
- FSH (Follicle-Stimulating Hormone): Targets Sertoli cells to support Spermatogenesis and produce Inhibin B.
Testosterone: The primary male androgen; crucial for spermatogenesis, secondary sexual characteristics, and libido. Exerts negative feedback on the hypothalamus and pituitary.
Inhibin B: Specifically inhibits FSH secretion from the pituitary.

⭐ Exam Favorite: Administration of exogenous testosterone leads to negative feedback on the H-P-G axis, causing ↓ GnRH, ↓ LH, and ↓ FSH. This results in decreased endogenous testosterone production, testicular atrophy, and infertility.

Male HPG Axis: GnRH, LH, FSH, Testosterone, Inhibin B

Spermatogenesis - The Production Line

Site: Seminiferous tubules, a process taking approximately 74 days.
Process: Begins at puberty. Diploid spermatogonia undergo mitosis & meiosis to become haploid spermatozoa.
Key Cells:
- Sertoli Cells: "Nurse" developing sperm; form the blood-testis barrier.
- Leydig Cells: Produce testosterone (stimulated by LH).

Spermatogenesis within the seminiferous tubule

⭐ Testes require a temperature of 35-36°C (~2°C below core body temp) for optimal spermatogenesis. Conditions like varicocele or cryptorchidism that ↑ temperature can impair fertility.

Sexual Response - The Main Event

Erection: Parasympathetic reflex (pelvic splanchnic n., S2-S4).
- Release of Nitric Oxide (NO) → ↑ cGMP → corporal smooth muscle relaxation → arterial inflow.
- Engorged corpora cavernosa compress subtunical venules, reducing venous outflow.
Emission: Sympathetic reflex (hypogastric n., T11-L2).
- Contraction of vas deferens, seminal vesicles, & prostate moves semen to the urethra.
Ejaculation: Somatic reflex (pudendal n.).
- Rhythmic contractions of bulbospongiosus & ischiocavernosus muscles expel semen.

📌 Mnemonic: Point (Parasympathetic) and Shoot (Sympathetic).

Neural pathways of male sexual response

⭐ Phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil) treat erectile dysfunction by preventing cGMP breakdown, thus prolonging vasodilation.

Androgen Effects - The Master Blueprint

Differentiation & Development:
- Internal male genitalia (Wolffian ducts): Testosterone
- External male genitalia & prostate: Dihydrotestosterone (DHT)
Secondary Sexual Characteristics (Puberty):
- Growth of penis, scrotum, seminal vesicles, prostate
- Deepening of voice (laryngeal growth)
- Male-pattern hair growth (androgenetic alopecia)
- Increased muscle mass & bone density
Metabolic & Other Effects:
- ↑ Libido & aggression
- ↑ Erythropoietin (EPO) → ↑ hematocrit
- ↑ VLDL & LDL; ↓ HDL

⭐ High-Yield: Testosterone is converted to the more potent DHT by 5α-reductase. Finasteride inhibits this enzyme, treating BPH and male pattern baldness.

Erection is a parasympathetic (S2-S4) response mediated by nitric oxide (NO) and cGMP.

Emission is a sympathetic (T11-L2) function, contracting the vas deferens.

Ejaculation involves sympathetic (bladder neck closure) and somatic (pudendal nerve) control.

Sildenafil (a PDE-5 inhibitor) enhances erection by increasing cGMP.

FSH stimulates Sertoli cells for spermatogenesis; LH stimulates Leydig cells for testosterone production.

Mnemonic: Parasympathetic for Pointing (erection), Sympathetic for Shooting (emission).

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