Why do many men go bald?

Last updated May 21, 2023

An investigation of the etiology of male pattern baldness (androgenetic alopecia, or AGA). This is purely a synthesis of work done by many others; I don’t claim that the information presented here is my own contribution or novel in any way. This is also not medical advice; Medical disclaimer.

I’m working on this article in pieces between other projects, and it’s only about a quarter complete right now. If you think I should prioritize this project, let me know on twitter. You can also check out Avoiding baldness for more practical information.

# Feedback between eicosanoids, sebum, and scalp flora

Human skin is equipped with sebaceous glands, which secrete an oily substance known as sebum. These glands are especially numerous on the face and scalp, and their dysfunction is implicated in a variety of skin disorders including acne and seborrheic dermatitis. One key histological feature of AGA is the enlargement of the sebaceous glands adjoined to hair follicles in the scalp, a phenomenon termed sebaceous hyperplasia, and the consequent excess production of sebum on the scalp. We will begin by tracing the causes of this symptom.

It has been shown that a particular signalling molecule, prostaglandin D2 (PGD2), is

PGD2 decomposes spontaneously to 15-deoxy-∆12,14-prostaglandin J2 (PGJ2), which is known to be capable of binding the nuclear receptor PPAR-γ. This receptor appears to instigate lipid generation in sebaceous glands1, and its activation by PGJ2 is known to induce lipogenesis2. PPAR-γ also has other functions, which we’ll investigate in more detail later.

As for why PGD2 is present in the scalp at all–it’s a member of the class of signalling molecules known as eicosanoids. These molecules are rapidly derived from lipids in the cellular membrane as part of the immediate response to an inflammatory stimulus… but what stimulus could exist in healthy scalp?

TODO: microorganisms like P. acnes, Malassezia, and porphyrins (inflammatory byproducts) found in scalp

It has been suggested (TODO: cite) that the following feedback loop may be active in balding scalp: This loop appears to be relevent to the progression of AGA. Antimicrobial and antifungal shampoos, such as those containing pyrithione zinc or ketoconazole, promote hair growth. Aspirin, which significantly inhibits PGD2 production, is known to promote hair growth. Finally, excess sebum unrelated to AGA is known to cause hair loss. (TODO: cite)

# Androgen activity

Of course, the above is not enough to explain the incidence of AGA. In most people, sebum production is normal in spite of the continuous presence of P. acnes and other lipophilic scalp flora. We also know that men are far more likely to go bald than women. Let’s examine the most obvious biochemical difference between men and women: the sex hormones.

Dihydrotestosterone (DHT) is produced from testosterone (T) by the 5α-reductase (5αR) family of enzymes in various tissues in the body. Both DHT and T are known as androgens, which act on cells by binding to the androgen receptor (AR), a nuclear receptor that influences transcription of various genes. DHT has a significantly greater affinity for the AR than T.

It is well-established that genetically male individuals with defective copies of the 5αR gene, and consequently no ability to synthesize DHT, do not develop male pattern baldness3. Furthermore, the 5αR-inhibiting drug finasteride is used clinically to promote hair growth3. Finally, individuals with AR dysfunction do not go bald4. The implication is clear: DHT must bind to the AR in order to trigger hair loss.

The hair follicle contains a collection of dermal papilla cells (DPCs), which influence the behavior of the follicle and are critical to proper hair growth; reduction in the number of DPCs in a follicle is enough to decrease hair quality and cause hair loss5. These cells, which express the AR, are believed to be the primary mediator of androgen action on the hair follicle. In fact, both the AR and 5αR are over-expressed in the DPCs of balding follicles compared to normal follicles 6, resulting in increased local DHT synthesis and activity.


  1. Trivedi, N. R., Cong, Z., Nelson, A. M., Albert, A. J., Rosamilia, L. L., Sivarajah, S., Gilliland, K. L., Liu, W., Mauger, D. T., Gabbay, R. A., & Thiboutot, D. M. (2006). Peroxisome Proliferator-Activated Receptors Increase Human Sebum Production. In Journal of Investigative Dermatology (Vol. 126, Issue 9, pp. 2002–2009). Elsevier BV. https://doi.org/10.1038/sj.jid.5700336 ↩︎

  2. Iwata, C., Akimoto, N., Sato, T., Morokuma, Y., & Ito, A. (2005). Augmentation of Lipogenesis by 15-Deoxy-Δ12,14-Prostaglandin J2 in Hamster Sebaceous Glands: Identification of Cytochrome P-450-mediated 15-Deoxy-Δ12,14-Prostaglandin J2 Production. In Journal of Investigative Dermatology (Vol. 125, Issue 5, pp. 865–872). Elsevier BV. https://doi.org/10.1111/j.0022-202x.2005.23866.x ↩︎

  3. Kaufman, K. D. (2002). Androgens and alopecia. In Molecular and Cellular Endocrinology (Vol. 198, Issues 1–2, pp. 89–95). Elsevier BV. https://doi.org/10.1016/s0303-7207(02)00372-6 ↩︎

  4. Randall, V. A. (2008). Androgens and hair growth. In Dermatologic Therapy (Vol. 21, Issue 5, pp. 314–328). Hindawi Limited. https://doi.org/10.1111/j.1529-8019.2008.00214.x ↩︎

  5. Morgan, B. A. (2014). The Dermal Papilla: An Instructive Niche for Epithelial Stem and Progenitor Cells in Development and Regeneration of the Hair Follicle. In Cold Spring Harbor Perspectives in Medicine (Vol. 4, Issue 7, pp. a015180–a015180). Cold Spring Harbor Laboratory. https://doi.org/10.1101/cshperspect.a015180 ↩︎

  6. Inui, S., & Itami, S. (2011). Molecular basis of androgenetic alopecia: From androgen to paracrine mediators through dermal papilla. In Journal of Dermatological Science (Vol. 61, Issue 1, pp. 1–6). Elsevier BV. https://doi.org/10.1016/j.jdermsci.2010.10.015 ↩︎