Androgen Related Alopecia

Lecture presented at KSHI in Seoul (2007)

by Prof Barry Stevens

As medical / scientific research continues, current opinion as expressed herein may change.

 Man is almost totally hair covered. Lanugo hair covers the foetus until the seventh month whereupon it is lost.   Postnatal hair is usually Vellus and Terminal.   Vellus hair is capable of change at puberty.   Terminal hair is the subject of this paper.

Throughout the ages of man, hair loss has been little understood. Research is progressively adding to our understanding of this complex vexatious problem which affects approx. 65% of caucasoid males and approx. 45% of caucasoid women by the age of 55 years. Currently we are evidencing treatments with lasers, Minoxidil, and too many ‘snake oil cures’ to list here. With the exception of hair follicle redistribution surgery (which has its limitations) no reliable treatments have been marketed.

Androgenetic and Androgenic Alopecias share a common factor – each is androgen related. The former is genetically inspired, the latter is acquired. Some recent reliable research into AGA comes from EHRS,  I incorporate some of their findings in this paper.

Androgenetic alopecia (AGA) is associated with the androgen dihydrotestosterone (5-alpha -DHT) which is the principle pathogen affecting androgen-sensitive hair follicles. It is apparent that individuals possessing enzyme type 2 steroid 5 alpha-reductase tend to develop AGA.   Individuals who lack it tend not to develop AGA.
AGA can therefore be categorised as a DHT (dihydrotestosterone) mediated process characterised by the inexorable miniaturization of androgen sensitive follicles.  AGA treatment aims therefore to stop or reverse the process of follicle miniaturisation. This may in theory be accomplished by preventing the formation of DHT via the drug Finasteride (Propecia) or by modulating DHT-binding to the androgen receptor with drugs e.g. Cyproterone Acetate.   However it has been demonstrated that other enzymes e.g. Aromatase and 3 alpha -hydoxysteroid-dehydrogenase may also be involved in the local metabolism of DHT. Aromatase which has been found in epithelial follicular tissue should diminish the quantity of intra-follicular testosterone available for conversion into DHT.
3 alpha -hydoxysteroid-dehydrogenase found to be present in the dermal papilla actually accelerates DHT dependent hair follicle activity (scalp hair loss and secondary sexual body hair increase).

Is it possible therefore that AGA may respond to increased levels of Aromatase and decreased levels of   3 alpha-hydoxysteroid-dehydrogenase. Further research is required.


Medical treatments currently available:
We accept that testosterone conversion to DHT by steroid 5 alpha-reductase plays a crucial role in AGA and Prostatomegaly. Research has shown that specific substances e.g. synthetic finasteride and dutasteride inhibit the conversion and may promote hair growth.
We are conscious that 5 alpha-reductase inhibiting drugs were found to potentially cause deformities in the male foetus of breeding mice so may be unsuitable as a treatment for AGA in males who may be fathering children. Whereas some current opinion suggests that abstention from the drug for a period of approximately three months will negate any risk, opinion amongst some prospective patients is one of concern.  Can we also ignore the possibility of long-term side effects – as yet unknown!

Future possible treatments
Non-steroidal 5 alpha – reductase inhibitors thought to be of future interest to research are:
Thujae Occidentalis Semen extract (leaves and fruits)
Epigallocatechin-3-gallate (Liao et al 1995)
Chlorophorin (Shimizu et al 2000)
Bisnapthoquinone derivative (Ishiguro et al 2000)`
Linolenic acid (Liang et al 1992)

Surgical treatments
Hair follicles cease to regenerate hairs due to androgenic (endocrine changes) or androgenetic (inherited androgen related factors). Rarely is this associated with hat wearing, circulatory or vitamin deficiency. Men and women are affected.
Female pattern loss may commence as a single coin-sized thinning patch in a central position just behind the fringe area. This thinning may extend to inculcate much of the scalp. One in five women will probably experience some degree of hair thinning associated with illness, ageing, hormonal changes after menopause or heredity. Wigs may be an answer. Topical prescription drugs may assist, but rarely is lost hair replaced-naturally.
Hair restoration surgery offers one possible solution. The best candidates for this procedure are sufferers of scalp damage and androgenic or androgenetic alopecia. The procedure involves the redistribution of an individual’s hair bearing follicles from safe ‘donor’ sites at the occiput to the balding regions. A skilled specialist surgeon can produce remarkable results dependent upon the availability of adequate numbers of donor follicles.

Techniques used: e.g. scalp reduction, micro-grafts (containing a single hair) and mini-grafts (containing two or three hairs), flaps and tissue-expansion. More than one technique may be employed during a procedure. As suitability to each technique depends on individual circumstances, one to one advice is essential

FUE (Follicular Unit Extraction) involves removing single-follicle hair grafts with 1mm. punches. This avoids lineal scarring and facilitates more rapid healing.
It is a time consuming procedure which costs more to perform and produces a lesser number of grafts per session. This new refinement of the old punch-graft method is at present – controversial.

Cloning (not yet an option)
Hair cloning or more correctly ‘Tissue engineering’ (hair follicle multiplication) research is currently occupying the interest of the biochemical and genetic research academics and clinicians world-wide. Cloning is an imminent possibility, as testing is currently underway at centres around the world.

The Currently Available Micro & Mini Grafts Procedure
I conducted much of the early pioneering work developing this technique in my own practice in London.

Points to be understood from the outset:
Only the patient’s hair follicles or those with a perfect tissue match (if obtainable) can be used. Areas of baldness may extend to exceed 200 sq. cm. Whereas some patients provide an abundance of donor hairs from densely populated donor sites, others less fortunate may provide insufficient numbers from which to harvest sufficient to provide even modest hair cover.
Subjects with excessive donor hair will never regain the density of hair coverage possessed prior to their hair loss, but this proven surgical technique can re-establish a level of hair cover at bald sites and increase the density at thin areas in the majority of individuals. This repositioned hair is expected to thrive in its new location for the remainder of natural life.
Several surgical sessions may be needed to achieve satisfactory fullness.
A healing interval of several months is recommended between sessions.
It may therefore take some years before the final result is achieved.
The cosmetic result may be influenced by: hair colour texture and levels of wave or curl.
All surgery carries some uncertainty and risk. However this is minimal when performed by a competent experienced surgeon.

Preparing for surgery
Your surgeon will advise you regarding: any prescriptive drugs being taken, diet, alcohol and smoking prior to surgery.
Venue: Hair reconstructive surgery is not usually performed in a hospital.

Anaesthesia : is usually ‘local’ and may be used in conjunction with sedation to make you more relaxed and comfortable. The procedure is therefore painless although some sensations (e.g. pressure) may be experienced. General anaesthesia may be used for more complex cases involving tissue expansion (Frechet Expander) or flap rotation.
The ‘donor’ area is primarily between the ears.   The hair there will be trimmed short so that the graft material can be easily accessed and harvested. The surgeon/doctor will use a scalpel to remove thin strips of hair-bearing scalp, which will be divided into tiny sections under dissection microscopy and transplanted into tiny slits at the recipient graft area.

Your surgeon may periodically inject small amounts of saline solution into the scalp to maintain proper skin strength. The donor site will require sutures and will leave a thin relatively imperceptible straight-line scar. The surrounding hair will conceal the stitches and any subsequent minor scaring.

After a session of surgery:
You should NOT drive yourself home.
You should ideally take a few days rest.
You may be required to wear a pressure bandage for a day or two.
Do NOT engage in risky sports (e.g. squash) until healing is complete.
Sutures may need to be removed at an appropriate time.
Caucasian hair growth rates vary between 0.09 – 1.35 cm per 28 days.

Other Procedures

Tissue Expansion:
Plastic surgeons employ this procedure in reconstructive surgery where burn wounds and other injuries have created significant skin loss. In hair reconstructive surgery a balloon-like device called a tissue expander is inserted beneath hair-bearing scalp adjacent to a bald area. Over a period of weeks the device is gradually inflated with salt water causing the skin to expand. This stretched hirsute skin then replaces the bald scalp.

Scalp reduction :
This procedure involves the removal of a section of bald scalp. The surrounding hairy skin is then made free and stretched to cover the area. The procedure is employed at the top and the back of the head but NOT at the frontal hairline. Extensive areas may benefit from this method.

After surgery :
Sensations include tightness and occasionally minor discomfort.
Any swelling or bruising should be reported. Bandaging if used will be removed the following day and the hair /scalp carefully washed. Sutures remain intact for up to 10 days.
Arrange some days off work following the surgery.
Resumption of certain sporting activities may be advisedly delayed.

Follow-up procedures:
Further cosmetic detail may be required to create more natural-looking results. e.g. mini-grafts or micro-grafts may be used to soften a hair line.
Transplanted hair follicles may reject their hair-shafts within the first 3 weeks of the procedure. This hair loss is temporary and new hair growth will appear within 8-16 weeks.

ANDROGENIC ALOPECIA (Androgen-related hair loss) in women.
Androgenic Alopecia in women is hair loss caused by follicular miniaturisation associated with endocrine changes and increased androgen presence. Accompanying factors may include: Polycystic ovarian syndrome, virilisation (and hirsutism), irregular menstruation, infertility, acne and seborrhoea oleosa.
Androgenic Alopecia in women warrants endocrinological investigation.
Menopausal Alopecia (androgenic alopecia) is associated with hormone changes. As oestrogen reduces hair-follicles become vulnerable to the effects of androgen exposure. Anti-androgen therapy may reduce further hair loss but is currently unlikely to initiate the return of lost hair.

Things to do
Until recently, no effective treatments have been available for certain alopecias in women.
Current options however may include the following drugs which may limit hair loss:
Systemic anti-androgen drugs e.g.
Spironolactone : Aldactone® Spiroctan®, Diatensec®.
Cyproterone acetate (Androcur®) Diane® or
Flutamide (Eulexin®).
Minoxidil : Regaine®
Finasteride : Propecia®is not currently indicated in women. However 5-alpha-reductase inhibitors (which prevent testosterone conversion and subsequent baldness in men) are currently being considered for female use. This may bring renewed possibilities in the treatment of this distressing disorder.
Surgical Hair Restoration (transplantation techniques)may be considered an option in certain cases.