Finasteride

Finasteride 1 mg and minoxidil 2–5% solution are the only approved treatment options for MPHL. Finasteride is a type 2 5-alpha-reductase inhibitor that decreases the conversion of testosterone to dihydrotestosterone (DHT), which is responsible for the miniaturization seen in MPHL. Finasteride efficacy is established in several long-term studies and meta-analysis [10–12]. In general, in young patients, vertex/mid-scalp areas have better response [12].

Dosage Regimen

Dose of finasteride is 1 mg/day (Table 8.1). The benefits of finasteride in MPHL treatment require indefinite use, as finasteride interruption is followed by gradual hair loss with return to the pre-treatment status within 1 year (Fig. 8.1). Starting treatment with finasteride does not prevent hair loss observed after interruption of topical minoxidil.

Table 8.1

Main first-line treatment options: male androgenetic alopecia

Medication	Treatment approval – US FDA	Mechanism of action	Dosage recommendations	Adverse effects
Systemic treatment
Finasteridea	Approved	5-α-reductase inhibitor	1 mg daily	Sexual side effects Mood disturbances
Dutasteride	Approved in several countries, e.g., Korea, Mexico, and Japan	5-α-reductase inhibitor	0.5 mg daily	Sexual side effects Mood disturbances
Oral minoxidil	Not approved/off-label	Unknown, possible antiandrogenic, vasodilatory, and anti-inflammatory effects	0.25–2.5 mg/day	Hypotension Lower limb edema Hypertrichosis
Topical treatment
Topical minoxidila	Approved	Unknown, possible antiandrogenic, vasodilatory, and anti-inflammatory effects	5% solution or foam twice daily	Hypertrichosis Contact dermatitis
Latanoprost	Not approved/off-label	Prolongs the anagen phase	0.03–0.1% solution once daily	Erythematous reaction
Topical 5-α-reductase inhibitors	Not approved/off-label	5-α-reductase inhibitor	0.1–1% solution once daily Compounded 2.5% liposomal gel three times a week	Systemic absorption leading to the same adverse effects of oral treatment Contamination of friends and family members

FDA Food and Drug Administration

^aAuthors’ first-line choices to start treatment

Finasteride in Women

Efficacy of finasteride is not well established in women, and its use in FPHL is off-label. Positive results have been reported in both pre- and postmenopausal women taking finasteride 2.5–5 mg in case reports, case series, and uncontrolled studies [22, 23] (Fig. 8.2). Women of childbearing age should use finasteride under strict birth control since it can cause feminization of the male fetus [24]. A concern about finasteride use in women is that conditions that result in relative estrogen excess or lack of androgen are associated with an increased risk of breast cancer [25]. Although there are no data showing that finasteride treatment increases risk of breast cancer, we avoid prescribing finasteride/dutasteride in women with a family or personal history of breast cancer (Table 8.2).

Table 8.2

Main first-line treatment options: female androgenetic alopecia

Medication	Treatment approval – US FDA	Mechanism of action	Dosage recommendations	Adverse effects
Systemic treatment
Spironolactonea	Not approved/off-label	Androgen receptor antagonist	100–200 mg once daily	Teratogenicity Breast tenderness Menstrual irregularities Increased urinary frequency Weight loss Hyperkalemia
Cyproterone acetate	Not approved/off-label	Androgen receptor antagonist Decreases testosterone levels	OCP containing cyproterone acetate 2 mg and ethinyl estradiol 0.035 mg Cyproterone acetate 25–50 mg on days 1–10 of menstrual cycle combined with OCP containing cyproterone acetate.	Teratogenicity Hepatotoxicity Weight gain Breast tenderness Decreased libido
Finasteride	Not approved/off-label	5-α reductase inhibitor	2.5–5 mg daily	Teratogenicity Sexual side effects Mood disturbances
Dutasteride	Not approved/off-label	5-α-reductase inhibitor	0.5 mg daily	Teratogenicity Sexual side effects Mood disturbances
Oral minoxidil	Not approved/off-label	Unknown, possible antiandrogenic, vasodilatory, and anti-inflammatory effects	0.25–1 mg/day	Hypertrichosis Hypotension Lower limb edema
Topical treatment
Topical minoxidila	Approved	Unknown, possible antiandrogenic, vasodilatory, and anti-inflammatory effects	2% solution 1 ml twice daily 5% foam once daily	Hypertrichosis Contact dermatitis
Latanoprost	Not approved/off-label	Prolongs the anagen phase	0.03–0.1% solution daily	Erythematous reaction
Topical 5-α-reductase inhibitors	Not approved/off-label	5-α-reductase inhibitor	0.1–1% topical solution once daily Compounded 2.5% liposomal gel three times a week	Systemic absorption leading to the same adverse effects of oral treatment Contamination of friends and family members

FDA Food and Drug Administration, OCP oral contraceptive pill

^aAuthors’ first-line choices to start treatment

Dutasteride

Dutasteride is a 5-alpha-reductase inhibitor that blocks the activity of both isoenzymes type 1 and type 2 and reduces DHT serum levels of 90% compared to 70% of finasteride [26]. Dutasteride 0.5 mg daily is approved for the treatment of BPH worldwide. It is approved for MPHL only in a few countries including Korea, Japan, and Mexico. Clinical studies and authors’ personal experience indicate that dutasteride is more effective than finasteride in MPHL [11, 27]. Some case reports and author’s personal experience show that concomitant therapy with both drugs can improve results, and a case series showed efficacy of dutasteride in men with MPHL that had a poor response to finasteride [28, 29].

Dosage Regimen

Dose of dutasteride is 0.5 mg/day (see Table 8.1). This is considered the best choice for men who did not respond to finasteride after 1 year (Fig. 8.3).

Spironolactone

Spironolactone is a potassium-sparing diuretic that is considered an antiandrogen, since it decreases the testosterone levels and blocks the androgen receptors in target tissues [32]. It has been used to treat FPHL for over 20 years with a good long-term safety profile and efficacy [33–35].

Cyproterone Acetate

Cyproterone acetate is an androgen receptor antagonist that directly blocks the DHT binding to its receptors and reduces the testosterone levels by decreasing follicle-stimulating and luteinizing hormone release. In most countries, but not in the USA, it is available alone or in combination with ethinyl estradiol as an oral contraceptive pill. The few existing studies addressing its therapeutic efficacy are controversial [35–37]. Side effects include hepatotoxicity, weight gain, decreased libido, breast tenderness, and feminization of the male fetus.

As previously mentioned, antiandrogen OCPs containing cyproterone acetate or drospirenone or dienogest may be a reasonable choice of birth control method in female patients using spironolactone, or 5-alpha-reductase inhibitors offering an additional antiandrogen therapeutic effect (see Table 8.2).

Safety and Side Effects

Minoxidil’s most common side effects include contact dermatitis and facial hypertrichosis. Ingredients of the vehicle, particularly propylene glycol, can cause skin irritation or allergy. True allergic reactions to minoxidil itself are rare. The foam formulation is an option in case of irritation because it does not contain propylene glycol. Hypertrichosis is reported more frequently in women than in men, but it is unclear whether this occurs because it is truly more common or just more noticeable. Hypertrichosis usually resolves 1–3 months after drug discontinuation. A transitory increase in hair shedding at the beginning of treatment is seen in some patients. Patients often read online about this side effect, and this is one of the main reasons patients discontinue or don’t start the treatment, so you absolutely need to discuss with the patient that this is just a sign of minoxidil efficacy, as it indicates that telogen follicles are re-entering the anagen phase. It usually lasts for a few weeks.

Although minoxidil is not advised for women who are pregnant, the American Academy of Pediatrics considers minoxidil to be compatible with lactation [45].

Dosage Regimen

In MPHL treatment, the recommended dosage for minoxidil 5% solution is 1 ml twice daily, while the dosage for the minoxidil 5% foam is half of a capful twice daily. Both formulations should be left in place for at least 4 hours (see Table 8.1).

For women, the recommended dosage is 1 ml of 2% minoxidil solution twice daily or half of a capful of the 5% foam formulation once a day (see Table 8.2).

Minoxidil should be applied after parting the hair from frontal hairline to the vertex. It can be applied on wet hair but should never be applied before going to bed to avoid facial exposure through the pillow.

Patients should be treated for at least 6 months prior to assess efficacy, and treatment should be prolonged indefinitely to maintain efficacy (see Figs. 8.1 and 8.2). Patients should also be informed that drug interruption will cause acute hair shedding after 3–4 months.