A Patient’s Guide: Management of Hair Loss in Polycystic Ovary Syndrome

Thinning hair due to the effects of male hormones (androgens) is called androgenic alopecia. It is a major source of psychological distress to women. This male-pattern hair loss is often seen in women with polycystic ovary syndrome (PCOS), congenital adrenal hyperplasia, and other disorders of male hormone excess. Additional causes may be hormonal changes secondary to a reduction of estrogen levels, which are physiological at menopause, as well as in thyroid disorders. Certain drugs, anemias, nutritional deficiencies, and severe illnesses and infections may be a trigger for diffuse hair loss. Associated with hormonal changes causing the alopecia are genetic and environmental factors which are responsible for the frequent finding of the onset of hair loss at the top of the head (vertex) and the angles of the frontal hair line. In many, the alopecia pattern may start as a triangular thinning, which I have labeled as the “triangle sign”, with gradual progression of hair loss from the midline frontal scalp line towards the vertex and sides of the scalp. In most women with androgenic alopecia the frontal hairline remains intact despite diffuse hair loss.

The average number of hairs lost in a day is about 100-150. It should be noted that it may take at least 20-25% of total loss of scalp hair before it may be visibly recognized by the woman. Thus an awareness of excessive hair loss at combing or after washing the hair, usually are the first signs of the onset of alopecia. Transient hair loss (telogen effluvium) may be another cause of hair loss a few months after the birth of a baby, and a return to a normal hair loss pattern often occur 3-4 months later.

The incidence is androgenic alopecia in PCOS is not clearly defined, but several reports vary from a prevalence of 40-70%, with a number of young women who may demonstrate this sign in their teens. Endocrinologists may also note androgenic alopecia in other disorders such as congenital adrenal hyperplasia and marked increased hair loss in women with rare disorders such as masculinizing neoplasm of the ovary or adrenal gland. Isolated alopecia as the only sign of male hormone excess is uncommon in PCOS, since the latter is usually associated with menstrual abnormalities and increased hair growth. It is helpful for each woman with alopecia to evaluate her own individual lifestyle and its relation to hair loss. Adequate nutrition is vital for healthy hair. For example, some who are on restricted diets may require dietary readjustment with selected supplements. Others may have chronic anemia and/or iron deficiency. Some vegetarians and those with minimal red meat intake may have reduced zinc intake in which with genetic factors may be more likely to have alopecia is association with or in the absence of PCOS.

The following are some hair care procedures and ways to improve scalp hair for everyone. Many of these listed below have been modified from the book by Philip Kingsley (Hair: An Owner’s Handbook; Aurum Press, 2003).

• Hair should be shampooed daily, and rinsed fully.
• Conditioning the hair removes tangles, particularly at the ends of the hair.
• Avoid insufficient rinsing, and minimize any tangling with a wide-toothed comb.
• Use of a brush with sharp bristles should be avoided. Smooth combs are preferable.
• Undefined stresses, hormonal medications (androgenic-like oral contraceptives, as well as a number of other medications may be associated with hair loss).
• Blow drying should be done with a hair dryer about 6 inches away. As the hair starts to dry reduce the heat gradually. Avoid blow drying hair from damp to dry to minimize hair damage, brittleness and split ends.
• Rollers have to be used carefully, and not tightly. Similarly, pins and clip use should be minimal and never while sleeping.
• If elastic bands and barrettes are used at all, they must not be tight. They have been noted to cause traction alopecia. Similarly, pulling the hair too tightly from the forehead may also lead to severe hair breakage.
• A habit of compulsively touching and pulling hair (trichotillomania) should be avoided.

Medical Treatments of Androgenetic Alopecia

A) Oral contraceptives (OCP) in combination with spironolactone
B) Diane-35 (containing cyproterone acetate and ethinyl estradiol)
C) OCP in combination with a 5-alpha reductase inhibitor
D) OCP with flutamide
E) Multiple drug therapy
F) Minoxidil

The medical management of androgenetic alopecia consists of a number of options. Unlike acne and hirsutism, medical management of hair loss is much more difficult. The listed drugs and options are more successful in slowing the progression of androgenic alopecia than actually reversing it. In PCOS, controlling the androgen overproduction of male hormones and stabilizing the disease is an essential first step prior to the use of these drugs for androgen effects on the hair follicle which include acne, hirsutism and alopecia. The use of insulin-sensitizers such as metformin are not very useful in the primary treatment of these skin changes but may be added to the treatment of the woman with PCOS with hair changes as well. Metformin treatment plays a major role in the management of the metabolic effects of insulin resistance in PCOS, and an antiandrogenic role has been reported. Further studies of the latter should be forthcoming.

A) Oral contraceptives (OCP) in combination with spironolactone

The most commonly used treatment is spironolactone in combination with OCP. Only those OCP with low androgenic potential should be used. Monotherapy with spironolactone alone, or OCP alone is of little value in arresting alopecia and the use of spironolactone may be associated with abnormalities in the genital development of a male fetus. Antiandrogens should be stopped at least 4-6 months prior to attempting to become pregnant. Spironolactone is a diuretic that has been in use for a long time, and found to have anti-androgenic effects. It works by blocking entry of the active metabolite of testosterone, namely, dihydrotestosterone (DHT), into the hair follicle. It has only a minimal effect on the hormone production of androgens and therefore the use of spironolactone with an OCP is indicated. The latter suppress ovarian stimulation of pituitary hormones which stimulate ovarian androgen production and also have a direct effect on androgen synthesis in the ovaries and to some extent the adrenal glands.

Studies suggest that OCP treatment does increase insulin resistance, which is not only present in PCOS, but to some extent in other androgen excess diseases such as congenital adrenal hyperplasia. For maximal effects on alopecia the dosage of spironolactone should be 150-200 mg daily in divided doses. A gradual dosage incremental program should be instituted. The most commonly encountered side effect of spironolactone is orthostatic dizziness on getting up quickly or suddenly bending over. Its diuretic effect also usually makes one urinate frequently and in hot weather increased water with increased salt intake is indicated. A rare side effect is a possible increase in serum potassium which should be monitored at 3-4 month intervals. An effect on slowing the progression of alopecia may be seen in 4-7 months. This treatment program is frequently helpful and widely used by endocrinologists in the treatment of alopecia, as well as hirsutism and stubbornly resistant cystic acne.

The combined use of any antiandrogen with OCP has the advantage of reducing the effect of hair shedding by several actions of OCP:

• they suppress the pituitary hormones, namely luteinizing hormone (LH) which stimulates the ovary to produce androgens;
• they increase a substance called sex hormone-binding globulin (SHBG) which allows more binding of testosterone to this protein, and
• it further allows biochemical effects of reducing conversion of testosterone to DHT. The use of OCP alone has only a minimal effect in reducing alopecia. Some of the benefits of OCP are the reduction of the incidence of uterine and ovarian cancer.

B) Diane-35 (containing cyproterone acetate and ethinyl estradiol)

Although it is not approved by the U.S. Food and Drug Administration (FDA), cyproterone acetate (CPA) is a potent progestin and antiandrogen which is effective when combined with an estrogen such as ethinyl estradiol in the form of Diane-35. It may be obtained in Canada and many other countries including those in Europe. CPA blocks the binding of the active androgen DHT at the receptor site of the hair follicle as well as other hormonal effects in the synthesis of androgens in the ovary and some effect on the release of LH by the pituitary gland. There are conflicting and no conclusive data as yet indicating a more effective antiandrogen treatment of Diane-35 when compared to the combined use of OCP and spironolactone. Some common side effects of Diane-35 include light-headedness, fluid retention, weight gain and rare reports of adrenal insufficiency.

C) OCP in combination with a 5-alpha reductase inhibitor

The effect of the non-hormonal “5-alpha reductase inhibitors” is the reduction of the formation of DHT from testosterone, which inhibits the interaction of DHT and the receptors of hair follicles which in the scalp may reduce the intensity of shedding hair. Many clinicians have expressed the view that there are no major differences of their clinical effects of reducing excessive hair growth (hirsutism) or reducing alopecia in women when compared to spironolactone. The earliest agent used in this category for alopecia as well as hirsutism has been finasteride (Proscar), a commonly used drug in men with prostate enlargement. There are no drug company comments suggesting its use as an antiandrogen in women, but neither is there for spironolactone.

Earliest effects of finasteride may be noted in 6 months and side effects usually are minimal with no change in the menstrual cycles, or blood levels of testosterone. It is essential for this drug to be combined with OCP to prevent conception, in that the effect on fetal genital development may be significant. In fact, it should be stressed that any woman considering fertility should stop the drug for at least 4-6 months prior to trying to conceive. Monotherapy with finasteride alone may be an option some postmenopausal women with alopecia. It is available in a 1.0 mg dosage form in men with significant hair loss (Propecia). A few preliminary studies suggest that another 5-alpha reductase inhibitor, dutasteride (Avodart), may be a therapeutic option in women whose hair loss is not controlled with finasteride. The dosage is 1 capsule of 0.5 mg daily. Definitive studies of the effectiveness of the drug as an antiandrogen for androgenic alopecia should be forthcoming.

D) OCP with flutamide

Flutamide (Eulexin) is a nonsteroidal pure antiandrogen in that it inhibits male hormonal effects in all tissues responsive to testosterone by inhibiting the effect of binding to the nucleus of these tissues. It has an earlier onset of action than all other androgens, i.e., usually within 3 months after start of treatment. An effective dosage in most patients may be as little as a 125 mg capsule twice a day. Its side effects include abdominal distress, diarrhea, and rarely fatal liver toxicity. Liver profiles in the blood must be carefully monitored in those receiving the drug. My personal view is to use it only in the most severe presentations of alopecia and those with such great emotional stress that it interferes with their lifestyle and emotional well-being.

E) Multiple drug therapy

The use of several antiandrogens in combination with an OCP may be tried by experienced endocrinologists familiar with these drugs.  The one I consider the best is a combination of spironolactone and a 5-alpha reductase inhibitor together with an OCP. There are few isolated reports regarding this form of treatment for severe androgenic alopecia.

F) Minoxidil

The topical use of minoxidil (Rogaine), an over-the-counter preparation, may be considered in early forms of alopecia either as a solo treatment or in combination with some of the above treatment choices. It is used frequently in women with various degrees of alopecia, but following discontinuation of the topical solution, the beneficial effect is gone. In some women there may be a mild degree of hair regrowth. The patient using Minoxidil should apply it carefully so as not to allow any drops to drip to the face, which may lead to undesired hirsutism of affected areas.

Conclusions

Although a number of treatments are effective in arresting androgenic alopecia, they are not FDA approved for use in women with alopecia, nor in hirsutism. It requires careful self-evaluation to exclude causes that may worsen its presence, and a thorough evaluation by your physician followed by an endocrinologist is an important step. Future studies will hopefully advance the introduction of new formulations which will benefit the woman with alopecia and reduce the emotional impact of this symptom.