Enclomiphene 10mg | Pregnenolone 25mg | Tadalafil 2.5mg | Anastrozole 0.2mg

Route: Oral capsule.

• Administer once daily by mouth, with or without food, at a consistent time each day.
• Swallow capsule whole; do not open or crush.
• Consistent dosing is important for tadalafil (continuous daily dosing for sustained PDE5 inhibition) and anastrozole (steady aromatase suppression).

This is a fixed-combination compounded capsule; dosing of each component is as specified (Enclomiphene 10mg / Pregnenolone 25mg / Tadalafil 2.5mg / Anastrozole 0.2mg once daily). Adjustments to any component require reformulation per prescriber direction. All dosing is prescriber-determined based on:

• Serum testosterone, LH, FSH, and estradiol (for enclomiphene and anastrozole dose guidance)
• Erectile function assessment (for tadalafil dose guidance)
• Serum pregnenolone and clinical neurosteroid/adrenal function assessment

• Enclomiphene: Pure estrogen receptor antagonist at the hypothalamus and pituitary; blocks negative feedback, increasing GnRH pulsatility, LH and FSH release, and testicular testosterone synthesis. Preserves spermatogenesis.
• Pregnenolone: First steroid in the steroidogenesis cascade, produced from cholesterol by mitochondrial CYP11A1 (P450scc). Provides the precursor pool for downstream hormone synthesis (DHEA, progesterone, cortisol, testosterone, estradiol). Independently acts as a neurosteroid: negative allosteric modulator of GABA-A receptors, positive modulator of NMDA receptors, and agonist at sigma-1 receptors — supporting cognition, memory, and neuroplasticity.
• Tadalafil: Selectively inhibits PDE5, the enzyme that degrades cyclic GMP (cGMP) in smooth muscle. Sexual stimulation triggers nitric oxide (NO) release from endothelium and nerve terminals in penile tissue; NO activates guanylate cyclase to produce cGMP, which relaxes smooth muscle and increases blood flow. PDE5 inhibition by tadalafil prolongs cGMP activity, facilitating and maintaining erection. The 2.5 mg daily dose provides continuous background PDE5 inhibition without peak-trough variability of on-demand dosing.
• Anastrozole: Competitive, reversible inhibitor of CYP19A1 (aromatase), the enzyme that converts androgens (testosterone, androstenedione) to estrogens (estradiol, estrone). In men, excess estradiol from elevated testosterone aromatization can cause gynecomastia, impair libido, and negatively feedback on the HPG axis. Low-dose anastrozole (0.2 mg/day) modulates estradiol levels to preserve an appropriate testosterone:estradiol ratio.

Clinical Context: This four-component combination is used in men with secondary hypogonadism who present with low testosterone, erectile dysfunction, and symptoms suggesting downstream neurosteroid insufficiency. The combination targets multiple aspects of male hormone health: HPG axis stimulation (enclomiphene), estrogen management (anastrozole), erectile function (tadalafil), and upstream steroidogenic support (pregnenolone). Anastrozole at 0.2 mg/day is a lower-than-standard dose, calibrated to prevent excessive estrogen suppression (too-low estradiol causes bone loss, mood deterioration, and lipid changes in men).

Monitoring:

• Serum testosterone (total and free), LH, FSH, and estradiol at 4–8 weeks and with dose adjustments.
• Serum pregnenolone and DHEA-S if clinically indicated.
• PSA at baseline and periodically (anastrozole/enclomiphene alter PSA thresholds).
• Bone density (DXA) if prolonged aromatase inhibition is anticipated.
• Lipid panel (anastrozole may adversely affect lipid fractions).
• Cardiovascular assessment: tadalafil is contraindicated with nitrates.

Contraindications:

• Concurrent nitrate therapy (organic nitrates, nitroglycerin, isosorbide) — tadalafil causes severe hypotension when combined with nitrates; absolutely contraindicated.
• Hypersensitivity to any ingredient.
• Severe hepatic impairment — tadalafil and anastrozole are hepatically metabolized; use with caution and dose-adjust as appropriate.
• Women (not indicated).

Warnings & Precautions:

• Tadalafil: Hypotension, especially with antihypertensives and alpha-blockers. Priapism (prolonged erection) — seek immediate medical attention if erection lasts >4 hours. Vision changes (non-arteritic ischemic optic neuropathy — rare). Hearing loss (rare).
• Anastrozole: Over-suppression of estradiol at higher doses causes bone mineral density loss, dyslipidemia, and mood deterioration in men. At 0.2 mg/day this risk is lower, but estradiol monitoring is still essential.
• Enclomiphene: Visual disturbances — discontinue and evaluate if blurred vision develops.
• Pregnenolone: May convert to androgenic or estrogenic metabolites variably; monitor downstream hormone levels.

Drug Interactions:

• Tadalafil + nitrates: Absolutely contraindicated (life-threatening hypotension).
• Tadalafil + alpha-blockers: Additive hypotension risk; initiate at lower doses.
• Anastrozole + estrogen-containing products: pharmacological antagonism; do not co-administer.
• CYP3A4 inhibitors (ketoconazole, ritonavir): increase tadalafil and anastrozole exposure.
• CYP3A4 inducers (rifampin, carbamazepine): reduce tadalafil efficacy.

Common Side Effects: Headache, flushing, nasal congestion, back pain (tadalafil); elevated estradiol (enclomiphene); arthralgia, hot flashes, dyslipidemia (anastrozole at higher doses); acne or mood changes (pregnenolone conversion to androgens). Individual component effects should be assessed at follow-up.

Store at controlled room temperature (20–25°C / 68–77°F). Protect from moisture and light. Keep in tightly sealed container out of reach of children. Use before the beyond-use date assigned by Genesis Compounding. Discard any remaining capsules after the beyond-use date.

Why are four medications combined in one capsule?

Each ingredient addresses a distinct aspect of male hormone health: enclomiphene restores testosterone production via the HPG axis; anastrozole prevents excessive estrogen conversion of that testosterone; pregnenolone supports upstream steroid precursor availability and neurosteroid function; and tadalafil supports erectile function independently of testosterone levels. Combining them improves adherence and allows the prescriber to optimize all four parameters simultaneously.

Why is the tadalafil dose only 2.5mg?

Daily low-dose tadalafil (2.5–5 mg/day) provides continuous, steady-state PDE5 inhibition, allowing erections to occur naturally in response to sexual stimulation without the peaks and troughs of on-demand dosing. This approach is well-studied and FDA-approved for daily tadalafil use in erectile dysfunction.

Why is the anastrozole dose only 0.2mg?

Standard anastrozole doses (1 mg/day) used in oncology aggressively suppress estradiol. In men using enclomiphene, only modest estrogen management is needed to prevent gynecomastia and maintain the testosterone:estradiol balance. Low-dose anastrozole (0.1–0.5 mg) is calibrated to prevent over-suppression of estradiol, which causes bone loss, mood changes, and dyslipidemia at very low levels.

Can I take this with my blood pressure medication?

Tadalafil can lower blood pressure, and combining it with antihypertensives or alpha-blockers may cause additive hypotension. The prescriber must review all concurrent medications before prescribing. Nitrate medications are absolutely contraindicated with tadalafil.

Is this FDA-approved?

None of the four components in this specific combination capsule are FDA-approved in this combined compounded form. Each active ingredient has its own regulatory status (tadalafil is FDA-approved for erectile dysfunction; anastrozole for breast cancer; enclomiphene was not FDA-approved for male hypogonadism; pregnenolone is not FDA-approved as a drug). Genesis Compounding prepares this as a patient-specific 503A preparation under prescriber direction.