Hirsutism medical therapy: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Hirsutism}} | {{Hirsutism}} | ||
{{CMG}} {{AE}} | {{CMG}}; {{AE}}{{EG}} | ||
==Overview== | ==Overview== | ||
Pharmacologic medical therapies for hirsituism include [[oral contraceptives]], [[antiandrogen therapy|androgen receptor blockers]], [[5-alpha-reductase inhibitor|5-alpha reductase inhibitors]], [[GnRH|gonadotrophin-releasing hormone]] ([[GnRH agonist]]), [[adrenal]] suppressive [[glucocorticoids]], [[insulin]]-sensitising agents, and biological modifiers of hair follicular growth. Treatment options are [[systemic therapy]] and [[topical|topical therapy]]. | |||
==Medical Therapy== | ==Medical Therapy== | ||
*Pharmacologic medical therapies for hirsituism include:<ref name="pmid20418968">{{cite journal| author=Sachdeva S| title=Hirsutism: evaluation and treatment. | journal=Indian J Dermatol | year= 2010 | volume= 55 | issue= 1 | pages= 3-7 | pmid=20418968 | doi=10.4103/0019-5154.60342 | pmc=2856356 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20418968 }} </ref> | |||
**[[Oral contraceptives]] | |||
**[[Antiandrogen therapy|Androgen receptor blockers]] | |||
* [[Oral contraceptives]] | **[[5-alpha-reductase inhibitor|5-alpha reductase inhibitors]] | ||
**[[GnRH|Gonadotrophin-releasing hormone]] ([[GnRH agonist]]) | |||
* [[ | **[[Adrenal]] suppressive [[glucocorticoids]] | ||
**[[Insulin]]-sensitising agents | |||
**Biological modifiers of hair follicular growth | |||
===Hirsutism=== | |||
* [[ | *1. '''Adult''' | ||
**1.1 '''Systemic therapy''' | |||
*** Preferred regimen (1): [[Ethinyl estradiol]] 30 μg '''''PLUS''''' [[norethindrone]] 1 mg PO daily over a 9-month period<ref name="pmid2136834">{{cite journal |vauthors=Murphy A, Cropp CS, Smith BS, Burkman RT, Zacur HA |title=Effect of low-dose oral contraceptive on gonadotropins, androgens, and sex hormone binding globulin in nonhirsute women |journal=Fertil. Steril. |volume=53 |issue=1 |pages=35–9 |year=1990 |pmid=2136834 |doi= |url=}}</ref> | |||
*** Preferred regimen (2): [[Mestranol]] 100 μg '''''PLUS''''' [[norethindrone]] 2 mg PO daily for about 2 weeks<ref name="GivensAndersen1974">{{cite journal|last1=Givens|first1=James R.|last2=Andersen|first2=Richard N.|last3=Wiser|first3=Winfred L.|last4=Fish|first4=Stewart A.|title=Dynamics of Suppression and Recovery of Plasma FSH, LH, Androstenedione and Testosterone in Polycystic Ovarian Disease Using an Oral Contraceptive|journal=The Journal of Clinical Endocrinology & Metabolism|volume=38|issue=5|year=1974|pages=727–735|issn=0021-972X|doi=10.1210/jcem-38-5-727}}</ref> | |||
*** Preferred regimen (3): [[Ethinyl estradiol]] 30 μg '''''PLUS''''' [[desogestrel]] 150 mcg PO daily for 4-7 months<ref name="pmid3156694">{{cite journal |vauthors=Dewis P, Petsos P, Newman M, Anderson DC |title=The treatment of hirsutism with a combination of desogestrel and ethinyl oestradiol |journal=Clin. Endocrinol. (Oxf) |volume=22 |issue=1 |pages=29–36 |year=1985 |pmid=3156694 |doi= |url=}}</ref> | |||
*** Preferred regimen (4): [[Spironolactone]] starting dose of 50 mg PO q12h; may be increased to 200 mg PO daily.<ref name="pmid1826112">{{cite journal |vauthors=Shaw JC |title=Spironolactone in dermatologic therapy |journal=J. Am. Acad. Dermatol. |volume=24 |issue=2 Pt 1 |pages=236–43 |year=1991 |pmid=1826112 |doi= |url=}}</ref> | |||
*** Alternative regimen (1): [[Cyproterone|Cyproterone Acetate]] 50-100 mg PO daily<ref name="pmid12749435">{{cite journal |vauthors=Lumachi F, Rondinone R |title=Use of cyproterone acetate, finasteride, and spironolactone to treat idiopathic hirsutism |journal=Fertil. Steril. |volume=79 |issue=4 |pages=942–6 |year=2003 |pmid=12749435 |doi= |url=}}</ref> | |||
*** Alternative regimen (2): [[Cyproterone|Cyproterone Acetate]] 2 mg '''''PLUS''''' [[ethinyl estradiol]] 35 μg PO daily<ref name="pmid14583927">{{cite journal |vauthors=Van der Spuy ZM, le Roux PA |title=Cyproterone acetate for hirsutism |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD001125 |year=2003 |pmid=14583927 |doi=10.1002/14651858.CD001125 |url=}}</ref> | |||
*** Alternative regimen (3): [[Finasteride]] 1-5 mg PO daily<ref name="pmid9854686">{{cite journal |vauthors=Faloia E, Filipponi S, Mancini V, Di Marco S, Mantero F |title=Effect of finasteride in idiopathic hirsutism |journal=J. Endocrinol. Invest. |volume=21 |issue=10 |pages=694–8 |year=1998 |pmid=9854686 |doi=10.1007/BF03350800 |url=}}</ref> | |||
*** Alternative regimen (4): [[Flutamide]] 125-250 mg PO q12h | |||
*** Alternative regimen (5): [[Bicalutamide ]] 25 mg PO daily<ref name="pmid20218823">{{cite journal |vauthors=Castelo-Branco C, Cancelo MJ |title=Comprehensive clinical management of hirsutism |journal=Gynecol. Endocrinol. |volume=26 |issue=7 |pages=484–93 |year=2010 |pmid=20218823 |doi=10.3109/09513591003686353 |url=}}</ref> | |||
*** Alternative regimen (6): [[Metformin]] 500-1000 mg PO q12h<ref name="pmid21856600">{{cite journal |vauthors=Paparodis R, Dunaif A |title=The Hirsute woman: challenges in evaluation and management |journal=Endocr Pract |volume=17 |issue=5 |pages=807–18 |year=2011 |pmid=21856600 |doi=10.4158/EP11117.RA |url=}}</ref> | |||
*** Alternative regimen (7): [[Rosiglitazone]] 4-8 mg PO daily | |||
*** Alternative regimen (8): [[Pioglitazone]] 10-30 mg PO daily<ref name="pmid23159176">{{cite journal |vauthors=Blume-Peytavi U |title=How to diagnose and treat medically women with excessive hair |journal=Dermatol Clin |volume=31 |issue=1 |pages=57–65 |year=2013 |pmid=23159176 |doi=10.1016/j.det.2012.08.009 |url=}}</ref> | |||
*** Alternative regimen (9): [[Leuprolide]] 7.5 mg IM '''''PLUS''''' [[estradiol]] 25-50 µg [[transdermal]] monthly<ref name="pmid22335316">{{cite journal |vauthors=Bode D, Seehusen DA, Baird D |title=Hirsutism in women |journal=Am Fam Physician |volume=85 |issue=4 |pages=373–80 |year=2012 |pmid=22335316 |doi= |url=}}</ref> | |||
*** Alternative regimen (10): [[Prednisone]] 5-10 mg PO daily<ref name="pmid22064667">{{cite journal |vauthors=Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, Pugeat M, Qiao J, Wijeyaratne CN, Witchel SF, Norman RJ |title=Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society |journal=Hum. Reprod. Update |volume=18 |issue=2 |pages=146–70 |year=2012 |pmid=22064667 |doi=10.1093/humupd/dmr042 |url=}}</ref> | |||
**1.2 '''Topical Therapy''' | |||
*** Preferred regimen (1): [[Eflornithine|Eflornithine hydrochloride]] 13.9% cream topical q12h<ref name="pmid18252793">{{cite journal |vauthors=Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, Shapiro J, Montori VM, Swiglo BA |title=Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline |journal=J. Clin. Endocrinol. Metab. |volume=93 |issue=4 |pages=1105–20 |year=2008 |pmid=18252793 |doi=10.1210/jc.2007-2437 |url=}}</ref> | |||
*** Preferred regimen (2): [[Finasteride]] 0.25% or 0.5% cream topical daily<ref name="pmid22658123">{{cite journal |vauthors=Farshi S, Mansouri P, Rafie F |title=A randomized double blind, vehicle controlled bilateral comparison study of the efficacy and safety of finasteride 0.5% solution in combination with intense pulsed light in the treatment of facial hirsutism |journal=J Cosmet Laser Ther |volume=14 |issue=4 |pages=193–9 |year=2012 |pmid=22658123 |doi=10.3109/14764172.2012.699680 |url=}}</ref> | |||
[[ | {| class="wikitable" | ||
!Group | |||
!Medicine | |||
!Dosage | |||
!Mechanism of action | |||
!Side effect | |||
!Notes | |||
|- | |||
| rowspan="3" |[[Oral contraceptive|Oral Contraceptive Pills (OCPs)]] | |||
|[[Ethinyl estradiol]]/<br>[[Norethindrone]] | |||
|30 μg /<br> 1.0 mg | |||
| rowspan="3" | | |||
* Inhibiting [[androgen]] secretion by the [[ovaries]] | |||
* Increasing [[sex hormone binding globulin|sex hormone binding globulin (SHBG)]] production by the [[liver]] | |||
* Inhibiting adrenal [[androgen]] production | |||
| rowspan="3" | | |||
* Increased risk of [[venous thromboembolism]] | |||
* [[Breast]] tenderness | |||
* [[Headache]] | |||
* [[Gastrointestinal]] symptoms | |||
| rowspan="3" | | |||
*Absolute contraindications | |||
**[[Smoking]] over the age of 35 (>15 cigarettes per day) | |||
**[[Hypertension]] | |||
**[[Ischemic heart disease]] | |||
**[[Migraine]] headache with [[focal neurological symptoms]] | |||
**[[Breast cancer]] (current) | |||
**[[Diabetes]] with [[retinopathy]]/[[nephropathy]]/[[neuropathy]] | |||
**Severe [[cirrhosis]] | |||
**[[Liver tumour]] ([[adenoma]] or [[hepatoma]]) | |||
|- | |||
|[[Mestranol]]/[[norethindrone]] | |||
|100 μg / 2mg | |||
|- | |||
|[[Ethinyl estradiol]]/<br>[[desogestrel]] | |||
|30 μg /<br> 150 mcg | |||
|- | |||
| rowspan="5" |[[Antiandrogens]] | |||
|[[Spironolactone]] | |||
|100-200 mg | |||
| | |||
* [[Antagonist]] of both [[aldosterone]] and [[androgen]] receptor | |||
* Competes with [[Dihydrotestosterone|dihydrotestosterone (DHT)]] for binding to the [[androgen]] receptor | |||
* Variable progestational activity | |||
* Decreases production of [[ovarian]] [[androgens]] | |||
* Inhibitory effect on 5 alpha-reductase activity (5-RA) | |||
* Competes with [[androgens]] for binding to [[sex hormone binding globulin|SHBG]] | |||
| | |||
* [[Abnormal uterine bleeding|Irregular menstrual bleeding]] | |||
* [[Headache]] | |||
* [[Hypotension]] | |||
* [[Nausea]] | |||
* Decreased [[libido]] | |||
| | |||
*Contraindications | |||
**[[Renal insufficiency]] | |||
**[[Hyperkalaemia]] | |||
|- | |||
|[[Cyproterone|Cyproterone Acetate]] | |||
|50-100 mg | |||
| rowspan="2" | | |||
*Competes with [[dihydrotestosterone]] for the [[androgen]] receptor | |||
*Inhibits 5α-reductase | |||
*Decrease in circulating [[testosterone]] and [[androstenedione]] levels through a reduction in circulating [[luteinizing hormone|luteinizing hormone (LH)]] | |||
| rowspan="2" | | |||
*[[Liver]] toxicity | |||
*[[Abnormal uterine bleeding|Irregular menstrual bleeding]] | |||
*[[Nausea]] | |||
*Decreased [[libido]] | |||
| rowspan="2" | | |||
- | |||
|- | |||
|[[Cyproterone|Cyproterone Acetate]]/<br>[[ethinyl estradiol]] | |||
| 2 mg /<br> 35 μg | |||
|- | |||
|[[Flutamide]] | |||
|125-250 mg | |||
| rowspan="2" | | |||
*Non-steroidal, [[competitive inhibitors]] of [[androgen]] receptor binding | |||
| rowspan="2" | | |||
*[[Hepatotoxicity]] | |||
*[[Fulminant liver failure]] | |||
| rowspan="2" | | |||
* Contraindication | |||
**[[Fulminant liver failure]] | |||
|- | |||
|[[Bicalutamide ]] | |||
|25 mg | |||
|- | |||
| rowspan="2" |[[5-alpha-reductase inhibitor|5-alpha reductase inhibitors]] | |||
|[[Finasteride]] | |||
|1-5 mg | |||
| rowspan="2" | | |||
*Type II inhibitor of the [[5-alpha-reductase|5α-reductase enzyme]] | |||
*Reduces the conversion of [[testosterone]] into [[dihydrotestosterone]] | |||
| rowspan="2" | | |||
*[[Feminisation]] of the male fetus | |||
*[[Liver dysfunction]] | |||
| rowspan="2" | | |||
- | |||
|- | |||
|[[Dutasteride]] | |||
|0.5 mg | |||
|- | |||
|[[GnRH|Gonadotrophin-releasing hormone]] ([[GnRH agonist]]) | |||
|[[Leuprolide]] | |||
|7.5 mg | |||
| | |||
*Suppress the [[hypothalamic-pituitary-gonadalaxis|hypothalamic-pituitary-ovarian axis]] | |||
*Inhibiting [[luteinising hormone|luteinising hormone (LH)]] and [[follicle-stimulating hormone|follicle-stimulating hormone (FSH)]] | |||
*Decreasing the secretion of [[androgens]] by the [[ovaries]] | |||
| | |||
*If not combined with [[estrogen]] | |||
**[[Menopausal]] symptoms | |||
**[[Hot flushes]] | |||
**[[Osteoporosis]] | |||
| | |||
*[[GnRH analogues]] not suggested for most women with hirsutism, because of: | |||
**Not seem to have advantages over other therapies | |||
**High price | |||
**Need additional [[estrogen]] to prevent [[bone loss]] and [[menopausal]] symptoms | |||
|- | |||
|[[Adrenal]] suppressive [[glucocorticoids]] | |||
|[[Prednisone]] | |||
|5-10 mg | |||
| | |||
*Used in cases of non-classic [[congenital adrenal hyperplasia]] | |||
*Suppress [[adrenocorticotropic hormone]] dependent [[adrenal]] [[androgen]] synthesis | |||
| | |||
*[[Weight gain]] | |||
*[[Osteoporosis]] | |||
*[[Adrenal suppression]] | |||
| | |||
- | |||
|- | |||
| rowspan="3" |[[Insulin]]-sensitising agents | |||
|[[Metformin]] | |||
|500-1000 mg | |||
| rowspan="3" | | |||
*Decrease [[hyperinsulinaemia]] by increasing [[insulin sensitivity]] | |||
*Lower [[insulin]] levels result in an increase of [[sex hormone binding globulin|SHBG]], thereby reducing the levels of circulating free [[androgens]] | |||
| rowspan="3" | | |||
*[[Gastrointestinal]] distress | |||
*Increased risk of [[cardiovascular events]] | |||
*[[Liver dysfunction]] | |||
*[[Lactic acidosis]] | |||
| rowspan="3" | | |||
*These are best choices for hirsutism along with [[insulin resistance]] | |||
*It is not suggested to prescribe these [[drugs]] just for hirsutism | |||
|- | |||
|[[Rosiglitazone]] | |||
|4-8 mg | |||
|- | |||
|[[Pioglitazone]] | |||
|10-30 mg | |||
|} | |||
==References== | ==References== |
Latest revision as of 22:59, 7 November 2017
Hirsutism Microchapters |
Diagnosis |
---|
Treatment |
Medical Therapy |
Case Studies |
Hirsutism medical therapy On the Web |
Risk calculators and risk factors for Hirsutism medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]
Overview
Pharmacologic medical therapies for hirsituism include oral contraceptives, androgen receptor blockers, 5-alpha reductase inhibitors, gonadotrophin-releasing hormone (GnRH agonist), adrenal suppressive glucocorticoids, insulin-sensitising agents, and biological modifiers of hair follicular growth. Treatment options are systemic therapy and topical therapy.
Medical Therapy
- Pharmacologic medical therapies for hirsituism include:[1]
- Oral contraceptives
- Androgen receptor blockers
- 5-alpha reductase inhibitors
- Gonadotrophin-releasing hormone (GnRH agonist)
- Adrenal suppressive glucocorticoids
- Insulin-sensitising agents
- Biological modifiers of hair follicular growth
Hirsutism
- 1. Adult
- 1.1 Systemic therapy
- Preferred regimen (1): Ethinyl estradiol 30 μg PLUS norethindrone 1 mg PO daily over a 9-month period[2]
- Preferred regimen (2): Mestranol 100 μg PLUS norethindrone 2 mg PO daily for about 2 weeks[3]
- Preferred regimen (3): Ethinyl estradiol 30 μg PLUS desogestrel 150 mcg PO daily for 4-7 months[4]
- Preferred regimen (4): Spironolactone starting dose of 50 mg PO q12h; may be increased to 200 mg PO daily.[5]
- Alternative regimen (1): Cyproterone Acetate 50-100 mg PO daily[6]
- Alternative regimen (2): Cyproterone Acetate 2 mg PLUS ethinyl estradiol 35 μg PO daily[7]
- Alternative regimen (3): Finasteride 1-5 mg PO daily[8]
- Alternative regimen (4): Flutamide 125-250 mg PO q12h
- Alternative regimen (5): Bicalutamide 25 mg PO daily[9]
- Alternative regimen (6): Metformin 500-1000 mg PO q12h[10]
- Alternative regimen (7): Rosiglitazone 4-8 mg PO daily
- Alternative regimen (8): Pioglitazone 10-30 mg PO daily[11]
- Alternative regimen (9): Leuprolide 7.5 mg IM PLUS estradiol 25-50 µg transdermal monthly[12]
- Alternative regimen (10): Prednisone 5-10 mg PO daily[13]
- 1.2 Topical Therapy
- Preferred regimen (1): Eflornithine hydrochloride 13.9% cream topical q12h[14]
- Preferred regimen (2): Finasteride 0.25% or 0.5% cream topical daily[15]
- 1.1 Systemic therapy
Group | Medicine | Dosage | Mechanism of action | Side effect | Notes |
---|---|---|---|---|---|
Oral Contraceptive Pills (OCPs) | Ethinyl estradiol/ Norethindrone |
30 μg / 1.0 mg |
|
|
|
Mestranol/norethindrone | 100 μg / 2mg | ||||
Ethinyl estradiol/ desogestrel |
30 μg / 150 mcg | ||||
Antiandrogens | Spironolactone | 100-200 mg |
|
| |
Cyproterone Acetate | 50-100 mg |
|
|
- | |
Cyproterone Acetate/ ethinyl estradiol |
2 mg / 35 μg | ||||
Flutamide | 125-250 mg |
|
| ||
Bicalutamide | 25 mg | ||||
5-alpha reductase inhibitors | Finasteride | 1-5 mg |
|
|
- |
Dutasteride | 0.5 mg | ||||
Gonadotrophin-releasing hormone (GnRH agonist) | Leuprolide | 7.5 mg |
|
|
|
Adrenal suppressive glucocorticoids | Prednisone | 5-10 mg |
|
- | |
Insulin-sensitising agents | Metformin | 500-1000 mg |
|
|
|
Rosiglitazone | 4-8 mg | ||||
Pioglitazone | 10-30 mg |
References
- ↑ Sachdeva S (2010). "Hirsutism: evaluation and treatment". Indian J Dermatol. 55 (1): 3–7. doi:10.4103/0019-5154.60342. PMC 2856356. PMID 20418968.
- ↑ Murphy A, Cropp CS, Smith BS, Burkman RT, Zacur HA (1990). "Effect of low-dose oral contraceptive on gonadotropins, androgens, and sex hormone binding globulin in nonhirsute women". Fertil. Steril. 53 (1): 35–9. PMID 2136834.
- ↑ Givens, James R.; Andersen, Richard N.; Wiser, Winfred L.; Fish, Stewart A. (1974). "Dynamics of Suppression and Recovery of Plasma FSH, LH, Androstenedione and Testosterone in Polycystic Ovarian Disease Using an Oral Contraceptive". The Journal of Clinical Endocrinology & Metabolism. 38 (5): 727–735. doi:10.1210/jcem-38-5-727. ISSN 0021-972X.
- ↑ Dewis P, Petsos P, Newman M, Anderson DC (1985). "The treatment of hirsutism with a combination of desogestrel and ethinyl oestradiol". Clin. Endocrinol. (Oxf). 22 (1): 29–36. PMID 3156694.
- ↑ Shaw JC (1991). "Spironolactone in dermatologic therapy". J. Am. Acad. Dermatol. 24 (2 Pt 1): 236–43. PMID 1826112.
- ↑ Lumachi F, Rondinone R (2003). "Use of cyproterone acetate, finasteride, and spironolactone to treat idiopathic hirsutism". Fertil. Steril. 79 (4): 942–6. PMID 12749435.
- ↑ Van der Spuy ZM, le Roux PA (2003). "Cyproterone acetate for hirsutism". Cochrane Database Syst Rev (4): CD001125. doi:10.1002/14651858.CD001125. PMID 14583927.
- ↑ Faloia E, Filipponi S, Mancini V, Di Marco S, Mantero F (1998). "Effect of finasteride in idiopathic hirsutism". J. Endocrinol. Invest. 21 (10): 694–8. doi:10.1007/BF03350800. PMID 9854686.
- ↑ Castelo-Branco C, Cancelo MJ (2010). "Comprehensive clinical management of hirsutism". Gynecol. Endocrinol. 26 (7): 484–93. doi:10.3109/09513591003686353. PMID 20218823.
- ↑ Paparodis R, Dunaif A (2011). "The Hirsute woman: challenges in evaluation and management". Endocr Pract. 17 (5): 807–18. doi:10.4158/EP11117.RA. PMID 21856600.
- ↑ Blume-Peytavi U (2013). "How to diagnose and treat medically women with excessive hair". Dermatol Clin. 31 (1): 57–65. doi:10.1016/j.det.2012.08.009. PMID 23159176.
- ↑ Bode D, Seehusen DA, Baird D (2012). "Hirsutism in women". Am Fam Physician. 85 (4): 373–80. PMID 22335316.
- ↑ Escobar-Morreale HF, Carmina E, Dewailly D, Gambineri A, Kelestimur F, Moghetti P, Pugeat M, Qiao J, Wijeyaratne CN, Witchel SF, Norman RJ (2012). "Epidemiology, diagnosis and management of hirsutism: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome Society". Hum. Reprod. Update. 18 (2): 146–70. doi:10.1093/humupd/dmr042. PMID 22064667.
- ↑ Martin KA, Chang RJ, Ehrmann DA, Ibanez L, Lobo RA, Rosenfield RL, Shapiro J, Montori VM, Swiglo BA (2008). "Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline". J. Clin. Endocrinol. Metab. 93 (4): 1105–20. doi:10.1210/jc.2007-2437. PMID 18252793.
- ↑ Farshi S, Mansouri P, Rafie F (2012). "A randomized double blind, vehicle controlled bilateral comparison study of the efficacy and safety of finasteride 0.5% solution in combination with intense pulsed light in the treatment of facial hirsutism". J Cosmet Laser Ther. 14 (4): 193–9. doi:10.3109/14764172.2012.699680. PMID 22658123.