Management of Hair Loss in Androgenic Disorders

Winter 2007	CARES Foundation, Inc.

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Management of Hair Loss in Androgenic Disorders

by Walter Futterweit, MD, FACP, FACE

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 congenital adrenal hyperplasia (CAH), polycystic ovary syndrome (PCOS), other hormonal disorders (thyroid disease), those associated with androgen excess and certain drugs (e.g., propranolol,Accutane), anemias, nutritional deficiencies, and severe illnesses. Associated with hormonal changes causing the alopecia are genetic and environmental factors which are responsible for the frequent finding of onset of hair loss at the top of the head (vertex) and the angles of the frontal hair line. In many, the pattern may start as a triangular thinning, which is called the “triangle sign.” There is gradual progression of hair loss at the frontal midline which progresses towards the vertex sides of the scalp. In most women with androgenic alopecia, the frontal hair line 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 about 20 to 25 percent 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 onset of alopecia. Transient hair loss (telogen effluvium) may be another cause of hair loss, for example a few months after the birth of a baby, and a return to normal hair loss may occur three to five months later. The incidence of androgenic alopecia in CAH is not clearly defined, but in another androgenic disorders, such as PCOS, it may vary from 40 to70 percent of these afflicted women. Experienced endocrinologists have seen similar data in women with CAH. In my experience, the severity of the alopecia appears to be somewhat more severe in CAH and appears at an earlier age than in patients with PCOS. It is important for each woman with alopecia to initially evaluate her own individual lifestyle and its relation to hair loss.
Hair Care 101: It is vital that the hair be shampooed daily and rinsed fully. Conditioning the hair removes tangles, with particular attention to the ends of the hair. Avoid insufficient rinsing, and minimize tangling with a widetoothed comb. Use of a brush with sharp bristles should be avoided. Smooth combs are preferable. Undefined stresses, hormonal medications (androgenic-like oral contraceptives and a number of other medications) possibly may be associated with hair loss. Blow drying should be done with the dryer about 6 inches away. As the hair starts to dry, reduce the heat gradually. It is necessary to avoid blow drying hair from damp to dry to avoid hair damage, brittleness and split ends. Rollers have to be used carefully, and not tightly. Pins and clips are also to be used cautiously, and never on while sleeping. If elastic bands and barrettes are used at all, they must not be tight. They may cause traction alopecia. Similarly, pulling the hair too tightly from the forehead may also lead to severe hair breakage. A habit of compulsively touching hair and pulling it (trichotillomania) should be seriously addressed.	Adequate nutrition is vital for healthy hair. For example, some who are on restricted diets may require dietary readjustment with selected supplements. Another cause of hair loss may be chronic anemia and/or iron deficiency. 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: Aurum Press, 2003). The medical management of androgenetic alopecia consists of a number of options: Oral contraceptives (OCP) in combination with spironolactone; Diane-35 (containing cyproterone acetate and ethinyl-estradiol); OCP in combination with a 5-alpha reductase inhibitor; OCP with flutamide; Multiple drug therapy; and Minoxidil. Unlike acne and hirsutism, medically controlling hair loss is much more difficult to treat. The listed drugs and options are more successful in slowing the progression of androgenic alopecia than actually reversing it. In CAH, controlling the overproduction of male hormones and stabilizing the disease is an essential first step prior to the use of these drugs. 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 fetal abnormalities in the genital development of a male fetus. It is important to realize that 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 suppresses ovarian stimulation by pituitary hormones which stimulate ovarian androgen production and also have a direct effect on androgen synthesis in the ovaries and to some extent in the adrenal glands.
	Some investigators also claim that spironolactone may increase insulin resistance, which is often seen in CAH. For maximal effects on alopecia the dosage should be 150-200 mg daily, in divided doses. A gradual dosage incremental program should be instituted.	Medical Treatments of Androgenetic Alopecia • Oral contraceptives (OCP) in combination with spironolactone • Diane-35 (containing cyproterone acetate and ethinyl estradiol) • OCP in combination with a 5-alpha reductase inhibitor • OCP with flutamide • Multiple drug therapy • Minoxidil
	The most commonly encountered side effect of spironolactone is dizziness on getting up quickly or suddenly bending over. Its diuretic effect also usually makes one urinate frequently, and in hot weather increased water consumption with an increased salt intake is indicated. A rare side effect is a possible increase in serum potassium which should be monitored at three to four month intervals. Women with salt-wasting CAH should be advised to have their physician check electrolytes regularly and watch closely for symptoms of dizziness and low blood pressure. An effect on slowing the progression of alopecia may be seen in five to seven months. This treatment program is frequently helpful and the most 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 a number of actions of the OCP: 1) they suppress the pituitary hormones, namely luteinizing hormone (LH) which stimulates the ovary to produce androgens; 2) they increase a substance called sex hormone binding globulin which allows more binding of testosterone to this protein, and 3) they further prevent biochemical effects of conversion of testosterone to DHT. The use of OCP alone has only a minimal effect in reducing alopecia. Other benefits of OCP, however, are the reduction of the incidence of uterine and ovarian cancer. Diane-35 (containing cyproterone acetate and ethinyl estradiol) Although it is not approved by the U.S. Food and Drug Administration (FDA) and not available within the US, 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 of Europe. There are conflicting and no conclusive data as yet indicating Diane-35 as a more effective antiandrogen treatment when compared to the combined use of OCP and spironolactone. CPA blocks the binding of the active androgen DHT at the receptor site of the hair follicle and has other hormonal effects in the synthesis of androgens in the ovary and some effect on the release of LH by the pituitary gland. Some common side effects of Diane-35 include light-headedness, fluid retention, weight gain and rare reports of adrenal insufficiency. 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, and this 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 the clinical effects of reducing excessive hair growth in women (hirsutism) or reducing alopecia in women with this therapy 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 statements suggesting its use in women, but neither is there for spironolactone. The earliest effects of this combination may be noted in six months, and the side effects usually are minimal with no change in the menstrual cycles. It is also essential for 5-alpha reductase inhibitors this drug to be combined with OCP to prevent conception, because the effect on fetal genital development may be significant. In fact, it should again be stressed that any woman considering fertility should stop the drug for at least four to six months prior to trying to have a family. Monotherapy with finasteride alone may be an option for some postmenopausal women with alopecia. Finasteride is available in a 1.0 mg dosage form in men with rapid hair loss (Propecia), while 5mg daily is recommended for women with androgenic alopecia. Several early studies suggest that another 5-alpha reductase inhibitor, dutasteride (Avodart), may be tried in women whose hair loss is not controlled with finasteride. The dosage is 1 capsule of 0.5 mg daily. Definitive studies of the effect of the drug as an antiandrogen for androgenic alopecia should be forthcoming. OCP with flutamide Flutamide (Eulexin) is a nonsteroidal antiandrogen that is a 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 antiandrogens, usually within three months after start of treatment. The dosage may be effective in most patients taking 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 tested frequently 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. Multiple drug therapy The use of several antiandrogens in combination with an OCP may be tried by experienced endocrinologists familiar with these drugs. The regimen I consider the best is a combination of spironolactone and a 5-alpha reductase inhibitor together with OCP. There are few adequate reports regarding this form of treatment for androgenic alopecia. 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 also used frequently in women with various degrees of alopecia. In some women there may be a mild degree of hair regrowth. The patient using Minoxidil should be careful to apply it carefully so as not to allow any drops to drip to the face which may lead to hirsutism of the 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 or acne. It requires careful study to exclude causes that may worsen its presence and a thorough evaluation by your physician followed by an endocrinologist is an important first step. Future studies will hopefully advance the introduction of new formulations which will benefit the woman with alopecia.

Dr. Walter Futterweit is a Medical Advisor to CARES Foundation. He is also Clinical Professor of Medicine in the Division of Endocrinology at Mount Sinai School of Medicine, NY .

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