Enclomiphene 25mg | Pregnenolone 25mg | Tadalafil 5mg | Anastrozole 0.2mg

Route: Oral capsule.

• Take one capsule by mouth once daily, at a consistent time, with or without food.
• Tadalafil 5 mg/day provides continuous background PDE5 inhibition; do not take additional PDE5 inhibitors.
• Swallow whole; do not open, crush, or chew the capsule.

All components are prescribed at fixed doses within this capsule. Dose modification of any single ingredient requires reformulation per prescriber direction:

• Enclomiphene 25mg: Phase III-studied dose for secondary hypogonadism; assess testosterone/LH/FSH at 4–8 weeks.
• Tadalafil 5mg: FDA-approved daily dose for erectile dysfunction.
• Anastrozole 0.2mg: Low-dose aromatase inhibition; monitor estradiol to avoid over-suppression.
• Pregnenolone 25mg: Typical neurosteroid/steroid precursor supplementation dose.

• Enclomiphene (25mg): Blocks hypothalamic and pituitary ERα/ERβ; disinhibits GnRH secretion, drives LH/FSH release, and maximally stimulates Leydig cell testosterone synthesis without suppressing spermatogenesis.
• Pregnenolone (25mg): Cholesterol-derived steroid synthesized by CYP11A1 in mitochondria; serves as the obligatory precursor for all steroid hormones including DHEA, progesterone, cortisol, testosterone, and estradiol. Directly modulates NMDA receptors (positive modulator via pregnenolone sulfate), GABA-A receptors (negative allosteric modulator), and sigma-1 receptors (agonist), supporting neuroplasticity, memory consolidation, and mood regulation independent of its conversion to downstream hormones.
• Tadalafil (5mg): Selective, reversible PDE5 inhibitor. Sexual stimulation → NO release → cGMP production → smooth muscle relaxation → penile blood flow increase. PDE5 normally degrades cGMP; tadalafil prolongs cGMP activity and vasodilation. At 5 mg/day, continuous inhibition facilitates erection on demand without requiring dose-on-demand timing.
• Anastrozole (0.2mg): Competitively inhibits CYP19A1 aromatase, reducing conversion of testosterone (and androstenedione) to estradiol (and estrone). Prevents excess estradiol from negative HPG feedback, gynecomastia, and estrogenic symptoms while preserving bone-protective estradiol levels in men.

Clinical Context: The 25 mg enclomiphene dose and 5 mg tadalafil daily dose represent the highest evidence-supported doses for their respective indications in men. This formulation is appropriate for patients requiring more aggressive testosterone normalization alongside erectile function support, neurosteroid supplementation, and estrogen management. The prescriber should assess which components are clinically indicated before selecting this versus the lower-dose 10mg/2.5mg formulation (ID 66).

Monitoring:

• Serum testosterone (morning, total and free), LH, FSH, and estradiol at 4–8 weeks.
• Estradiol: Target estradiol in the physiologic male range (20–40 pg/mL); adjust anastrozole if outside this range.
• PSA at baseline and 6–12 month intervals.
• Bone density (DXA) with prolonged aromatase inhibitor use.
• Lipid panel (anastrozole class effects on lipids).
• Cardiovascular assessment: tadalafil contraindicated with nitrates.
• Blood pressure (tadalafil may cause mild hypotension).

Contraindications:

• Concurrent organic nitrate therapy (nitroglycerin, isosorbide) — absolutely contraindicated with tadalafil (severe, potentially fatal hypotension).
• Hypersensitivity to any component.
• Severe hepatic impairment.
• Primary (hypergonadotropic) hypogonadism.
• Women — not indicated.

Warnings & Precautions:

• Tadalafil: Hypotension with antihypertensives/alpha-blockers; priapism (prolonged erection >4 hours — medical emergency); rare NAION (non-arteritic anterior ischemic optic neuropathy) and hearing loss.
• Anastrozole: Over-suppression of estradiol leads to bone loss, dyslipidemia, and mood/libido deterioration — monitor estradiol at each follow-up; keep estradiol in physiologic male range.
• Enclomiphene: Visual disturbances — discontinue and evaluate immediately if vision changes occur.
• Pregnenolone: Variable conversion to androgens or estrogens in individuals; monitor downstream hormones.

Drug Interactions:

• Tadalafil + nitrates: Absolutely contraindicated.
• Tadalafil + alpha-blockers, antihypertensives: Additive hypotension.
• CYP3A4 inhibitors (ritonavir, ketoconazole): Increase tadalafil and anastrozole exposure significantly.
• Anastrozole + estrogen preparations: Pharmacological antagonism; do not co-administer.

Common Side Effects: Headache, back pain, flushing, nasal congestion (tadalafil); estradiol fluctuation, gynecomastia (enclomiphene/anastrozole interplay); arthralgias (anastrozole); acne or neurosteroid-related mood/sleep changes (pregnenolone).

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.

Why does this version use tadalafil 5mg instead of 2.5mg?

Tadalafil 5 mg/day is the FDA-approved daily dose for erectile dysfunction (versus 2.5 mg, which is the approved starting dose for patients who may need lower exposure). The prescriber selects between 2.5 mg and 5 mg based on clinical response, tolerability, and the degree of erectile dysfunction. 5 mg provides greater PDE5 inhibition while remaining within the approved daily dosing range.

How does anastrozole interact with enclomiphene?

Enclomiphene increases testosterone production, some of which aromatizes to estradiol. Anastrozole inhibits this conversion, preventing excess estradiol accumulation (gynecomastia, estrogenic side effects, negative HPG feedback). However, too much anastrozole suppresses estradiol below physiologic male levels, causing bone loss, mood deterioration, and sexual side effects. The 0.2 mg dose is a conservative adjustment; prescribers should monitor estradiol and titrate accordingly.

What is pregnenolone doing in this formulation?

Pregnenolone is the master steroid precursor synthesized from cholesterol in the adrenal cortex and brain. It is the upstream substrate for DHEA, cortisol, testosterone, and other steroids. Additionally, pregnenolone acts directly as a neurosteroid — modulating NMDA and GABA-A receptor activity to support memory, cognition, and mood — effects that are independent of its conversion to downstream hormones.

Is the 25mg enclomiphene dose safe?

25 mg/day is the highest dose evaluated in phase III randomized trials. It was found to normalize testosterone without significant safety signals beyond those known for lower doses. The most clinically relevant concerns are estradiol elevation and rare visual disturbances, both of which are monitored in follow-up. Anastrozole co-inclusion in this formulation mitigates estradiol-related risks.

Is this product FDA-approved?

Tadalafil is FDA-approved at 5 mg/day for erectile dysfunction; anastrozole is FDA-approved for breast cancer. Enclomiphene and pregnenolone are not FDA-approved for these uses. This specific multi-ingredient combination capsule is not FDA-approved; it is a patient-specific 503A compounded preparation from Genesis Compounding.