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Alopecia due to high androgen index contraceptives

Graves, Katelyn Y., PhD; Smith, Benjamin J., PA-C, DFAAPA; Nuccio, Brigitta C., MPAS, PA-C

Journal of the American Academy of PAs: August 2018 - Volume 31 - Issue 8 - p 20–24
doi: 10.1097/01.JAA.0000541476.24116.c4
CME: Women's Health

ABSTRACT Adverse reactions to hormonal contraceptives are a common patient concern. Alopecia, an adverse reaction to androgen activity caused by the progestin component of hormonal contraceptives, can cause considerable psychosocial distress for women. This article discusses how to identify the level of androgen activity in certain progestins, how increased androgen activity can lead to hair loss, and alternatives for patients experiencing androgenic alopecia due to high androgen index contraceptives.

In the PA program at Florida State University in Tallahassee, Fla., Katelyn Y. Graves is on the research faculty, Benjamin J. Smith is director of didactic education, and Brigitta C. Nuccio is an assistant professor. The authors have disclosed no potential conflicts of interest, financial or otherwise.

Earn Category I CME Credit by reading both CME articles in this issue, reviewing the post-test, then taking the online test at http://cme.aapa.org. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of August 2018.

Figure

Figure

Box 1

Box 1

Alopecia of any nature can be extremely distressing, given the psychosocial implications of losing hair. Although hormonal contraceptives can be associated with alopecia, certain progestins in hormonal contraceptives can lead to androgen-sensitive adverse reactions, even in women with normal hormone levels. For example, levonorgestrel has a high androgenic index, which can cause adverse reactions in women who are sensitive to androgenic activity. In comparison, desogestrel has very low androgenic index and drospirenone is mildly antiandrogenic.1 If women associate alopecia with hormonal contraception, they may be more likely to avoid this highly effective form of contraception.2

Box 2

Box 2

Although most sexually active women have used hormonal contraception or an intrauterine device (IUD) at some point, many have discontinued the methods due to dissatisfaction or adverse reactions.2 For example, 30.4% of patients using oral contraceptives have discontinued at least one formulation, and more than half (62.9%) of those who discontinued did so because of adverse reactions.2 Many undesirable adverse reactions to hormonal contraception (such as weight gain, acne, mood changes, decreased libido, and alopecia) are a result of the progestin used.3 Clinicians who understand the characteristics of available progestins can help their patients choose the best contraceptive method.

Telling patients that hormonal contraceptives vary in androgen index may help women who have experienced or are concerned about alopecia feel more comfortable about using low androgen index contraceptives. Clinicians who recognize alopecia symptoms related to hormonal contraceptive use can help patients recover more quickly. Because patients may have long waits to see specialists, primary care providers can perform the appropriate laboratory work and evaluation while the patient awaits the initial appointment with a specialist. In some cases, the hair loss may resolve based on the primary care provider's recommendations, eliminating the need for a referral. Ruling out other causes of hair loss, such as polycystic ovarian syndrome (PCOS) or thyroid disorders, may lead to an earlier diagnosis, reduced patient anxiety, and increased patient confidence.

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HAIR GROWTH CYCLE

The hair growth cycle has four phases:

  • Anagen, lasting from 2 to 6 years, in which the hair is actively growing.
  • Catagen, which lasts days to a few weeks, and is a degenerative stage in which hair stops growing.
  • Telogen, lasting about 3 months, is a resting phase.
  • Shedding stage, sometimes called the exogen stage.

About 90% of hair follicles are in the anagen phase at a given time.4 Estimates of daily hair shedding vary, with a typical range of 50 to 150 hairs lost per day.4,5

Alopecia occurs when one or more of the growth cycles is interrupted. For example, in androgenic alopecia, the anagen phase is shortened, meaning hairs spend less time growing before eventually being shed. Understanding the hair growth cycle will help clinicians when evaluating patients with alopecia and classifying the cause of their hair loss.

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Causes

Alopecia has numerous causes (Table 1). Hormonal contraceptives can cause hair loss through:

  • androgenic alopecia, characterized by a gradual thinning of the hair. Androgens shorten the anagen phase and also lead to shorter and thinner hair follicles.6 Though the process is not fully understood, it may be due to testosterone converting into dihydrotestosterone (DHT) and interrupting the hair growth cycle.6 Increased DHT appears to miniaturize scalp follicles, leading to progressively thinner hair.5 This article focuses on increased androgenic activity due to high-androgen hormonal contraceptives. However, other hormonal dysregulation can lead to androgenic alopecia, and in some cases, it may be genetic female pattern hair loss.4
  • telogen effluvium, or increased shedding caused by the hair follicle going into the telogen phase prematurely. Telogen effluvium generally occurs 3 to 4 months after a precipitating event, such as discontinuation of a hormonal contraceptive that lengthens the anagen phase, starting certain medications, a major illness, or childbirth.7 This form of alopecia generally resolves after a few months.
TABLE 1

TABLE 1

Patients may experience androgenic alopecia and telogen effluvium as a result of using hormonal contraceptives. In patients susceptible to androgenic alopecia (that is, the condition runs in the family) or those already afflicted (patients who have already experienced androgenic alopecia in other forms such as female pattern hair loss), telogen effluvium can lead to androgenic alopecia.7

FIGURE 1

FIGURE 1

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EFFECTS OF HORMONAL CONTRACEPTIVES

Hormonal contraception is available in two forms: those containing estrogen (ethinyl estradiol) and progestin, and those containing only a progestin.1 Oral contraceptives are available in both formulations; IUDs, subcutaneous implants, and injections contain only progestins.

A common way to categorize the wide variety of progestins in hormonal contraceptives is by generation.8 Progestins that bind to the androgen receptor are considered to have androgen activity, though the level, or index, varies between the first three generations of progestins (Table 2). A higher androgen index leads to an increase in the testosterone metabolite DHT, which leads to hair loss by shortening the hair growth cycle. First-generation progestins (estranes such as norethisterone) have higher androgenic indexes and more adverse reactions than second-generation and third-generation progestins. Progestins interact with the progesterone receptor but also can interact with receptors for androgen or estrogen. These differences in interactions with hormone receptors result in differing effects across progestin types.8,9

TABLE 2

TABLE 2

The second-generation progestins, norgestrel and levonorgestrel, bind to androgen receptors and are considered higher in androgen index than the third-generation and newer classes of progestins.1 Desogestrel, norgestimate, and etonogestrel are third-generation progestins that have very low androgen indexes.

Finally, the newest progestins, such as chlormadinone acetate (not available in the United States) and drospirenone, have mild antiandrogenic activity.

Contraceptives with androgenic effects, especially first-generation and second-generation progestins, can induce androgenic alopecia and chronic telogen effluvium, and can worsen the effects for women who already have androgenic alopecia.10

Androgen activity also may be counteracted by activity involving estrogen receptors.1,11 In combined oral contraceptives, estrogen can counteract androgenic effects by increasing sex hormone binding globulin (SHBG), which then binds to testosterone and reduces androgenic effects.1,12 This effect is greater for oral contraceptives containing 30 mcg ethinyl estradiol, compared with those containing lower levels. Additionally, combined oral contraceptives with third-generation or newer progestins have the greatest increase of SHBG because the androgenic effects of second-generation progestins inhibit the estrogenic effect of increased SHBG.1

The estrogen in combined oral contraceptives may aid hair growth by extending the anagen phase of the hair growth cycle.12 Despite some conflicting evidence, the increase in female pattern hair loss following menopause suggests that estrogen promotes hair growth. High estrogen levels during pregnancy are thought to contribute to the longer duration of the anagen phase, which can be followed by an increase in the number of hairs in the telogen phase postpartum when estrogen decreases again.13

Progestin-only hormonal contraceptives may make alopecia worse because they lack estrogen to counteract androgen effects. Accurate rates of hair loss due to hormonal contraceptives are difficult to find due to differing methodologies, studies funded by pharmaceutical companies, and hair loss often being combined with hirsutism when categorizing adverse reactions. In a study of more than 17,000 women in Finland with the levonorgestrel IUD, 15.7% reported hair loss; this adverse reaction was significantly associated with premature removal of the device.14 Unlike the other progestin-only methods, the etonogestrel implant only shows an initial decrease in estrogen, with levels returning to normal afterward.15

Medroxyprogesterone acetate is not included in Table 2 as it generally is not classified with the other groups of progestins. Although medroxyprogesterone acetate is considered to have no androgenic effect, studies have reported androgenic adverse reactions, including hair loss, and therefore this should be taken into account.16

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DIFFERENTIAL DIAGNOSIS

Assess the duration, timing, and type of hair loss. Telogen effluvium is associated with increased shedding beginning about 3 months after a precipitating event; androgenic alopecia is characterized by gradual, patterned hair thinning. Shedding in telogen effluvium is abrupt, diffuse, and nonscarring. Once the cause is removed, increased shedding can last 3 to 6 months. Chronic telogen effluvium is characterized by at least 6 months of increased shedding, and in the cases where medication is the cause, also will generally resolve in 3 to 6 months after the medication is discontinued. Rule out other causes of alopecia due to hormonal dysregulation, such as PCOS.17 Androgenic alopecia is a clinical trait in PCOS, along with hirsutism, menstrual dysfunction, and obesity. According to the Androgen Excess and PCOS Society (AE-PCOS), the diagnosis of PCOS must be based on the presence of at least two of the following three criteria: chronic anovulation, hyperandrogenism (clinical or biological), and polycystic ovaries.18

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DIAGNOSTIC EVALUATION

Obtain a complete medical history and perform a complete physical examination to rule out other causes of alopecia. Diagnostic testing should include a complete blood cell (CBC) count, and thyroid-stimulating hormone (TSH), ferritin, vitamin D, dehydroepiandrosterone sulfate (DHEA-S), and testosterone levels.19

Performing a hair pull test can provide insight on the degree of hair shedding, but these tests are low in sensitivity and may be distressing to patients who are already losing hair. This test is performed by gently pulling on one patch of hair and counting the number of hairs that come loose. A positive pull test, on a patch of 60 hairs, is found if 6 or more hairs come loose and this finding is repeated on three or more areas of the scalp.10 A positive hair pull test indicates telogen effluvium but does not necessarily exclude androgenic alopecia, as hair pull tests can be positive in the beginning of the disorder.10

Pull tests generally are negative in patients with androgenic alopecia; this type of alopecia also can be recognized by the gradual thinning of hair on the patient's central scalp.20 A scalp biopsy is a more accurate method of determining the type of alopecia but is invasive and patients should be referred to a specialist if a biopsy is necessary.4

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TREATMENT

If the patient is using hormonal contraception, consider the androgen index of the progestin (Table 2). The level of ethinyl estradiol in the contraceptive also is an important factor because estrogenic effects can counteract androgenic effects. Thus, women who are experiencing androgenic alopecia, whether due to contraceptives or not, may find more benefit from combined oral contraceptives with 30 mcg ethinyl estradiol.21 Patients taking combined oral contraceptives that contain third-generation progestins or drospirenone may be at increased risk of venous thromboembolism.22

For patients who develop increased hair shedding 3 to 4 months after starting a high androgen index contraceptive, and for whom other potential causes have been ruled out, switching to a low androgen index contraceptive may be beneficial if the shedding does not resolve in 6 months.7,23 Gradual hair thinning in a patient using a high androgen index contraceptive, in the absence of other causes, indicates androgenic alopecia.20 If a patient has been experiencing chronic shedding (6 months or more) or hair thinning and is on a high androgen index contraceptive, consider prescribing a less androgenic contraceptive and referring the patient to a dermatologist for further evaluation.

Patients normally do not need to wait between discontinuing their current hormonal contraceptive and starting a new one.21 However, advise patients to use a supplemental form of birth control until the new medication reaches effective levels.

For patients who cannot tolerate estrogen, consider nonhormonal contraceptives such as the copper IUD, or less-androgenic progestin-only contraceptives, such as the etonogestrel implant.21 If the hair loss does not resolve within 3 to 6 months after the patient switches to a low androgen contraceptive, topical minoxidil (2% solution) or topical corticosteroids (typically clobetasol 0.05%) may be administered twice daily.17 Minoxidil and topical corticosteroids also may be used in combination.17 Refer the patient to a dermatologist if hair loss does not resolve within 3 to 6 months.

If at any time in the evaluation of the patient, the diagnosis or potential causes of alopecia are unclear, prompt referral to dermatology is appropriate.

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CONCLUSION

Primary care providers are likely to be the first point of contact for patients experiencing hair loss. A patient with alopecia is likely to experience decreased self-esteem, increased anxiety, and decreased quality of life. Determining the cause of the alopecia as efficiently as possible can help patients reach the best-possible outcome.

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REFERENCES

1. De Leo V, Musacchio MC, Cappelli V, et al Hormonal contraceptives: pharmacology tailored to women's health. Hum Reprod Update. 2016;22(5):634–646.
2. Daniels K, Mosher WD. Contraceptive methods women have ever used: United States, 1982-2010. Natl Health Stat Report. 2013;(62):1–15.
3. Brynhildsen J. Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks. Ther Adv Drug Saf. 2014;5(5):201–213.
4. Trüeb RM. Systematic approach to hair loss in women. J Ger Soc Dermatol. 2010;8(4):284–297, 284-298.
5. Semalty M, Semalty A, Joshi GP, Rawat MS. Hair growth and rejuvenation: an overview. J Dermatol Treat. 2011;22(3):123–132.
6. Levy LL, Emer JJ. Female pattern alopecia: current perspectives. Int J Womens Health. 2013;5:541–556.
7. Tosti A, Pazzaglia M. Drug reactions affecting hair: diagnosis. Dermatol Clin. 2007;25(2):223–231.
8. Sitruk-Ware R. New progestagens for contraceptive use. Hum Reprod Update. 2006;12(2):169–178.
9. Sitruk-Ware R, Nath A. Characteristics and metabolic effects of estrogen and progestins contained in oral contraceptive pills. Best Pract Res Clin Endocrinol Metab. 2013;27(1):13–24.
10. Gordon KA, Tosti A. Alopecia: evaluation and treatment. Clin Cosmet Investig Dermatol. 2011;4:101–106.
11. De Leo V, Di Sabatino A, Musacchio MC, et al Effect of oral contraceptives on markers of hyperandrogenism and SHBG in women with polycystic ovary syndrome. Contraception. 2010;82(3):276–280.
12. Sonthalia S. Hair restoration in androgenetic alopecia: looking beyond minoxidil, finasteride and hair transplantation. J Cosmetol Trichol. 2016:1–13.
13. Yip L, Rufaut N, Sinclair R. Role of genetics and sex steroid hormones in male androgenetic alopecia and female pattern hair loss: an update of what we now know. Australas J Dermatol. 2011;52(2):81–88.
14. Backman T, Huhtala S, Blom T, et al Length of use and symptoms associated with premature removal of the levonorgestrel intrauterine system: a nation-wide study of 17,360 users. Int J Obstet Gynaecol. 2000;107(3):335–339.
15. Spencer AL, Bonnema R, McNamara MC. Helping women choose appropriate hormonal contraception: update on risks, benefits, and indications. Am J Med. 2009;122(6):497–506.
16. Tyler KH, Zirwas MJ. Contraception and the dermatologist. J Am Acad Dermatol. 2013;68(6):1022–1029.
17. Blumeyer A, Tosti A, Messenger A, et al Evidence-based (S3) guideline for the treatment of androgenetic alopecia in women and in men. J Dtsch Dermatol Ges. 2011;9(suppl 6):S1–S57.
18. Goodman NF, Cobin RH, Futterweit W, et al American Association of Clinical Endocrinologists, American College of Endocrinology, and Androgen Excess and PCOS Society disease state clinical review: guide to the best practices in the evaluation and treatment of polycystic ovary syndrome—part 1. Endocr Pract. 2015;21(11):1291–1300.
19. Barbor M. Three patterns of female hair loss. Dermatol Times. 2015;36(9):44–45.
20. Patel M, Harrison S, Sinclair R. Drugs and hair loss. Dermatol Clin. 2013;31(1):67–73.
21. Harper DM, Wilfling LE, Blanner CF. Contraception. In: Textbook of Family Medicine. 9th ed. Philadelphia, PA: Elsevier; 2016.
22. Guerra JA, López-Muñoz F, Álamo C. Progestins in combined contraceptives. J Exp Clin Med. 2013;5(2):51–55.
23. Brough KR, Torgerson RR. Hormonal therapy in female pattern hair loss. Int J Womens Dermatol. 2017;3(1):53–57.
Keywords:

alopecia; progestin; high androgen index; oral contraceptives; androgenic; hormonal

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