Anti-Müllerian Hormone (AMH): Physiology and Clinical Utility

‍PATHCHAT Edition No. 28
Please contact your local Ampath pathologist for more information.

Author: Dr. Marita du Plessis

Physiology of Anti-Müllerian Hormone (AMH)

🔹 What is AMH?

• AMH, also known as Müllerian-inhibiting substance (MIS), is a 140 kDa dimeric glycoprotein.
• It belongs to the TGF-β (Transforming Growth Factor Beta) superfamily.
• It plays a key role in sexual differentiation and ovarian function.

🔹 AMH in Male Development:

• Expressed by Sertoli cells from approximately 8 weeks’ gestation.
• Causes involution of the Müllerian ducts, preventing development of female reproductive structures.
• AMH absence or receptor dysfunction leads to Müllerian duct differentiation into the uterus, oviducts, and upper vagina in males and females.

🔹 AMH in Boys:

• Peaks at 3 months of age during transient activation of the hypothalamic-pituitary-gonadal axis (mini-puberty).
• Declines by one year, remaining stable until puberty.
• At puberty, AMH decreases due to increased testosterone.
• Elevated AMH suggests androgen insensitivity.

🔹 AMH in Girls:

• AMH levels increase from undetectable levels at birth to small peaks at 3 months (mini-puberty).
• Secreted by granulosa cells of primary and pre-antral follicles.
• Predicts ovarian follicular reserve.
• Inhibits follicular recruitment and FSH-dependent follicle growth.
• Gradually declines with age, becoming undetectable post-menopause.

📌 AMH levels fluctuate slightly during the menstrual cycle but are not significant enough to require phase-specific sampling.

Clinical Utility of AMH Measurement

🔹 1. Evaluating Testicular Function in Ambiguous Genitalia or Cryptorchidism
✅ AMH measurement helps distinguish between:

• Cryptorchidism (undescended testes present) → Detectable AMH.
• Anorchidism (absent testes) → Undetectable AMH.
• Androgen insensitivity syndrome → High AMH due to lack of testosterone suppression.

2. Assessing Ovarian Reserve

✅ Why is AMH the Best Marker for Ovarian Reserve?

• AMH is produced continuously by granulosa cells in small ovarian follicles.
• More reliable than FSH, estradiol, or inhibin B.
• Unaffected by pregnancy.
• Minimally affected by oral contraceptives (recommend testing after 4 weeks off medication).
• Declines before FSH increases in premature ovarian failure.

📌 AMH can confirm premature ovarian failure and predict menopausal transition.

3. AMH in In Vitro Fertilization (IVF) Treatment

✅ Higher AMH Levels Predict:

• Better response to ovarian stimulation.
• Higher number of retrievable oocytes.
• Greater correlation with antral follicle count (AFC), FSH, inhibin B, and oestradiol.

🔹 AMH-Based Prediction of IVF Response:

✔ Negligible/Non-Responders:

• AMH <0.17 ng/mL (<1.2 pmol/L)
• Likely to produce no viable eggs.

✔ Poor Responders:

• AMH 0.17–1.21 ng/mL (1.2–8.6 pmol/L)
• Expected ≤2 eggs at retrieval.

✔ Normal Responders:

• AMH 1.22–2.30 ng/mL (8.7–16.4 pmol/L)
• Expected 3–20 eggs at retrieval.

✔ High/Excessive Responders:

• AMH >2.30 ng/mL (>16.4 pmol/L)
• Expected >20 eggs at retrieval.
• Higher risk for ovarian hyperstimulation syndrome (OHSS).

📌 AMH levels decrease during controlled ovarian hyperstimulation (COH) due to follicular growth and reduction in small antral follicles.

4. AMH as a Marker for Polycystic Ovarian Syndrome (PCOS)

✅ Why is AMH Elevated in PCOS?

• Higher number of small follicles.
• Increased AMH production per follicle.
• Can serve as a diagnostic marker when ultrasound is unavailable.

✅ AMH in PCOS Diagnosis:

• High specificity (92%) and sensitivity (67%) for PCOS.
• Higher AMH levels in amenorrhoeic vs. oligomenorrhoeic PCOS patients.
• Metformin therapy reduces AMH levels and antral follicle count.

✅ AMH & Assisted Reproductive Technology in PCOS:

• Women with very high AMH (>10 ng/mL) are at high risk of OHSS.
• Mildly elevated AMH improves ovulation induction success rates.

5. AMH as a Tumor Marker for Granulosa Cell Tumors

✅ Granulosa cell tumors account for 10% of ovarian tumors.

• AMH is elevated in 76–93% of cases.
• Combining AMH with CA-125 improves monitoring of treatment response and recurrence detection.

Specimen Collection & Testing Requirements

✅ Preferred Sample:

• Serum collected in a serum separator tube (SST).
• Must be centrifuged within 5 hours of collection.
• Stable at room temperature for 1 day.

✅ Cost of AMH Testing:

• Approximately R600.

Key Takeaways for Clinicians

✅ AMH is a reliable marker for ovarian reserve, superior to FSH.
✅ AMH testing helps diagnose premature ovarian failure and predict menopause.
✅ In IVF, AMH predicts response to ovarian stimulation and OHSS risk.
✅ AMH is a useful marker for PCOS and correlates with follicle count.
✅ In males, AMH helps evaluate testicular function and cryptorchidism.
✅ AMH is a tumor marker for granulosa cell ovarian tumors.

References

1. Aksglaede L et al. (2010). Changes in Anti-Müllerian Hormone (AMH) Throughout the Life Span: A Population-Based Study of 1,027 Healthy Males from Birth to Age 69. J Clin Endocrinol Metab, 95(12): 5357–5364.
2. Hagen CP et al. (2010). Serum Levels of AMH as a Marker of Ovarian Function in 926 Healthy Females from Birth to Adulthood. J Clin Endocrinol Metab, 95(11): 5003–5010.
3. La Marca A & Volpe A. (2006). AMH in Female Reproduction: Is Circulating AMH a Useful Tool? Clin Endocrinol, 64: 603–610.
4. Tal R et al. (2014). AMH and PCOS: Correlation with Phenotypes and ART Outcomes. Am J Obstet Gynecol, 211: 59–61.
5. Pellatt L et al. (2010). AMH and PCOS: A Mountain Too High? Reproduction, 139: 825–833.