What are the underlying causes of hair loss in women?

Underlying Causes of Female Hair Loss

Female pattern hair loss (FPHL) is primarily a clinical diagnosis with multifactorial etiology that includes genetic predisposition, hormonal influences (particularly androgens in some but not all women), and potentially nutritional deficiencies, though the relationship between FPHL and androgen excess remains inconsistent—most affected women have normal androgen levels. 1

Primary Etiologic Factors

Genetic and Non-Androgenic Mechanisms

• Genetic predisposition is the dominant factor, though the specific genes involved in FPHL differ substantially from male pattern hair loss 2
• FPHL can occur in women with:
  • Normal circulating androgen levels (most common presentation) 1
  • Complete absence of androgens 1
  • Absent androgen receptors 1
• This indicates that isolated FPHL should NOT be considered a sign of hyperandrogenism when androgen levels are normal 1

Androgen-Related Mechanisms (When Present)

When hyperandrogenism is present, the mechanism involves:

• Increased DHT production in hair follicles
• Enhanced 5α-reductase activity converting testosterone to DHT
• Androgen receptor activation leading to follicular miniaturization 1, 3

However, this represents a subset of FPHL patients, not the majority 1

Secondary Contributing Factors

Endocrine Disorders to Evaluate

All patients with FPHL should be assessed for androgen excess (mandatory), while evaluation of other endocrine factors is optional but recommended 1:

• Thyroid dysfunction - affects hair cycle regulation 1
• Hyperprolactinemia - relationship to hair loss unclear but warrants evaluation 1
• Polycystic ovary syndrome (PCOS) - when present with hyperandrogenism 3

Nutritional Deficiencies (Controversial Evidence)

Iron deficiency:

• Evidence is conflicting and the relationship remains uncertain 1
• Some studies show lower ferritin in FPHL patients, others show no difference
• Critical finding: Iron supplementation in patients with low-normal ferritin (<70 mg/L) did NOT improve hair loss 1
• Given frequent iron deficiency in premenopausal women generally, causation is unproven

Vitamin D deficiency:

• 62% of FPHL patients had low 25-hydroxyvitamin D levels in one study 1
• Well-controlled studies proving causation are lacking 1

Zinc deficiency:

• 15% of FPHL patients had low zinc levels 1
• Mean zinc levels were lower in FPHL patients versus controls in one study 1
• Evidence for treatment benefit is insufficient 1

Metabolic Factors (Emerging Evidence)

Recent research suggests:

• Obesity and metabolic syndrome may exacerbate hair loss through oxidative stress and enhanced androgen signaling 4
• Hypertriglyceridemia is associated with FPHL in obese women 4
• Oxidative stress pathways may contribute independently of androgens 4

Other Causes of Female Hair Loss (Differential Diagnosis)

Beyond FPHL, other distinct entities include:

• Chronic telogen effluvium - diffuse shedding without pattern 1, 5
• Alopecia areata - autoimmune, patchy loss with preserved follicles 6
• Scarring alopecias:
  • Lichen planopilaris (including diffuse variants that mimic FPHL clinically) 5
  • Central centrifugal cicatricial alopecia 7
  • Frontal fibrosing alopecia 1
• Trichotillomania - behavioral hair pulling 6

Diagnostic Approach

The diagnosis is primarily clinical 1, requiring:

1. Detailed history focusing on:

   • Pattern of hair loss (central scalp thinning with preserved frontal hairline)
   • Duration and progression
   • Menstrual history and signs of hyperandrogenism
   • Medications and systemic illness

2. Physical examination:

   • Scalp evaluation for inflammation or scarring
   • Assessment for other signs of androgen excess (hirsutism, acne)
   • Dermatoscopic examination when diagnosis unclear 1

3. Laboratory evaluation 1:

   • Mandatory: Total and free testosterone (using high-quality assay: LC/MS preferred)
   • Recommended: SHBG, DHEAS, thyroid profile, prolactin
   • Optional: Ferritin, vitamin D, zinc (though treatment benefit unproven)

4. Scalp biopsy - reserved for cases where clinical diagnosis is uncertain or to differentiate from other causes 1, 5

Key Clinical Pitfalls

• Do not assume all FPHL is androgen-driven - most women have normal androgen levels 1
• Do not over-supplement nutrients without proven deficiency - iron supplementation at low-normal levels does not improve FPHL 1
• Do not miss scarring alopecias - diffuse variants of lichen planopilaris can mimic FPHL clinically but require different management 5
• Biotin supplementation should be avoided due to interference with diagnostic tests 7