New womens Spironolactone hairloss trial

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http://www.watoday.com.au/national/...ays-for-bald-women-20081206-6sws.html?page=-1

Drug trial to end bad hair days for bald women

* Jill Stark
* December 6, 2008

FOR men coping with baldness, the solution can be as simple as shaving their head. But for women the effects can be devastating. Losing their hair often means a loss of femininity and sense of self-esteem. With rates of anxiety and depression high among sufferers, some even resort to tattooing their heads to hide thinning patches on their scalps.

But a world-first trial at a Melbourne hospital is offering hope to the estimated 700,000 Australian women affected by severe hair loss.

Doctors at St Vincent's aim to prove that a drug used to reduce excessive facial and body hair can stop hair loss on the scalp of women, as well as stimulate partial hair growth in up to a third of sufferers.

They hope that this evidence will encourage doctors — many of whom tell women there is no treatment for hair loss — to prescribe the tablets more widely.

Eventually the plan is to develop the drug in an implant form, which would allow women to receive treatment for up to three years at a time without the need for a daily tablet. A patch like those used by smokers trying to kick the habit would also be trialled.

Rod Sinclair, professor of dermatology at St Vincent's, said up to 55 per cent of Australian women will suffer hair loss during their lifetime. While the condition often develops after menopause, Professor Sinclair said up to 10 per cent of teenage girls and 20 per cent of women in their 30s were affected. There is no known cure and treatment options are limited.

"Often these women come to us in tears. A lot of the time they are so distressed they end up on antidepressants. It can make them feel very guilty for being so upset about something that is purely cosmetic, but it affects their whole sense of femininity and they feel as if everybody is staring at them," Professor Sinclair said.

"Hundreds of millions of dollars have been invested in finding new treatments for male baldness, but with women it is still very much a taboo subject."

Around 80 women suffering hair loss are being recruited to trial the drug Spironolactone. While there is some evidence the drug is effective in arresting the progress of female baldness, the trial will be the first in the world to provide medical proof of its efficacy. Half of the women will take a placebo; the rest will take the drug.

Sebastiana Biondo, a clinical psychologist and hair loss expert from the Skin and Cancer Foundation, said she had seen an increase in the number of women affected by baldness in recent years. She said it should not be viewed as a cosmetic problem.

"It's hard to get funding for research and treatment because it's not seen as a health issue, but it affects their quality of life and psychological wellbeing in a really profound way," Ms Biondo said.

"Women invest a lot of their self-esteem in their hair and their appearance, so this can be a debilitating condition. I see women who are very distressed and become quite obsessed and paranoid about it."

The cause of female hair loss is still unknown but it is thought genetics and stress may play a role. Normally, three hairs grow out of one pore. While men lose all the hair from the pore, women tend to lose two, usually leaving them with a thin covering of hair rather than complete baldness.

Ms Biondo said some women used camouflage makeup or tattoos to hide bald or thinning patches on the scalp. "They do it out of desperation. They'll try anything. Some spend thousands at hair loss clinics or with herbal medications they find on the internet. They're very vulnerable."

Some forms of alopecia — a severe form of hair loss — can cause complete baldness including loss of eyebrows and eyelashes. "Often people ask these women if they've got cancer or if they've had chemotherapy, which can be very upsetting. It seems to be socially acceptable for men to be bald but for women it's completely different," she said.

From 'big hair' to barely there: a survivor's story

MOST teenage girls can overcome a bad hair day with a blow-dryer and some product, but for a few it's not that simple. And at an age when appearance is everything, it can be devastating.

Loukia Gauntlett was 17 when she first realised her hair was falling out. The process was so gradual it took an observant classmate to point it out.

"I walked into a classroom one day and one of my friends said, 'I can see through your hair.' I must have been sitting in front of a window and the light was shining in a particular way. I went home and we realised that a lot of my hair had started to disappear. It had become very thin across the top and around the back," Ms Gauntlett said.

Coming to terms with female pattern baldness as a teen was distressing. Little was known about the condition and Ms Gauntlett felt alone and conspicuous.

"Growing up, I was the one in the family with big hair, it was down below my bum for most of my childhood, so to lose it was pretty horrible. When I went to see doctors there was a lot of talk of options for men like hair transplants and lotions that they rub into their hair, but not much targeted at women. I felt like a bit of a freak. I'd go to hairdressers and they wouldn't really know what to do with my hair. For a 17-year-old, that's pretty devastating."

Now 29, Ms Gauntlett, of North Melbourne, has learnt to disguise her condition by keeping her hair short and putting highlights through it to cover up the lightness of her scalp. While her mother was convinced the hair loss was caused by her turning vegetarian for a year in her teens, Ms Gauntlett believes it may be genetic as an aunt and grandmother both suffer from the condition.

The thinning does not seem to have progressed since her teens, but in a bid to regrow new hair she is taking part in the trial at St Vincent's and began taking medication in October. She has already noticed some new hairs sprouting.

"If it works that will be great, but if not at least I'll have been part of an attempt at a solution. I've come to realise that I have friends who have beautiful hair and they're not happy with it, so I'll just live with it. It's just hair, we don't need it to survive."

The Age
 

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Australasian Journal of Dermatology
Volume 48 Issue 1 Page 43-45,
February 2007

CASE REPORT

Treatment of female pattern hair loss with a combination of spironolactone and minoxidil

Carlijn Hoedemaker, Sylvia van Egmond and Rodney Sinclair
Department of Dermatology, St Vincent’s Hospital, University of Melbourne, and Department of Medicine and Skin and Cancer Foundation, Melbourne, Victoria, Australia

Summary

A 53-year-old woman with clinical evidence of female pattern hair loss and histological evidence of androgenetic alopecia was initially treated with the oral antiandrogen spironolactone 200 mg daily. Serial scalp photography documented hair regrowth at 12 months; however, the hair regrowth plateaued, and at 24 months there had been no further improvement in hair density. Twice daily therapy with topical minoxidil 5% solution was then introduced and further regrowth documented, confirming the additive effect of combination therapy.

Introduction

Female pattern hair loss is a common, psychologically distressing, age-related, androgen-mediated condition that presents with increased hair shedding and reduction in hair volume over the mid-frontal scalp.1

Binding of dihydrotestosterone to cellular androgen receptors induces susceptible scalp hairs to undergo a progressive and orderly transition from terminal to vellus hairs to produce patterned baldness. Antiandrogen therapy with either spironolactone or cyproterone acetate is commonly used to treat FPHL, as is topical minoxidil.2 The mechanism of action of minoxidil is unknown, but does not involve androgen pathways.3 The use of topical minoxidil together with an oral antiandrogen might have an additive effect; however, combination therapy has not been previously reported.

Case Report

A 53-year-old woman, with a past history of hypertension for which she was treated with felodipine, presented with a 6-month history of increased hair shedding, combined with a noticeable reduction in hair volume over the mid-frontal scalp. On specific questioning she stated that the volume of her hair, when held back in a ponytail, had decreased by 30% over the past 6 months. No obvious trigger for the hair loss was identified on history. On examination she was noted to have minimal bi-temporal recession. Her hair pull test was negative. Her mid-frontal scalp hair density was estimated as Stage 3 on the clinical grading scale (Sinclair scale).

Screening biochemical investigations were normal. A horizontally sectioned punch biopsy from the mid-frontal scalp confirmed androgenetic alopecia with a terminal to vellus hair ratio of 3:1.

As spironolactone is known to be effective in the treatment of hypertension as well as FPHL, felodipine was replaced by oral antiandrogen therapy with spironolactone. She was commenced at an initial dose of 25 mg daily, which was incrementally increased to 200 mg daily over 6 weeks, carefully monitoring her blood pressure.

Serial scalp photography was used to document response to therapy at 6-monthly intervals. Compared with baseline (Fig. 1), the photograph taken at 12 months (Fig. 2) revealed noticeable improvement, particularly in the mid-frontal area of the scalp. Two years after commencing spironolactone, her hair regrowth plateaued (Fig. 3). The patient was instructed to apply 1 mL twice daily of minoxidil 5% solution. Follow up 1 year later revealed additional regrowth (Fig. 4), and the patient was instructed to continue with combination therapy indefinitely. Follow up over an additional 4 years shows that the regrowth seen with combination therapy has been maintained (Fig. 5).

Discussion

Spironolactone is an androgen receptor antagonist. In addition, it reduces the levels of the cytochrome P450-dependent enzymes 17?-hydroxylase and desmolase, both of which are required for androgen synthesis.4 Spironolactone has been reported to be effective in the treatment of FPHL at a dosage of 200 mg daily.5

In this patient, improvement in hair regrowth was seen after 12 months therapy with spironolactone 200 mg.

Hair regrowth with topical minoxidil is well documented in literature.6 Minoxidil prolongs anagen, shortens telogen and converts partially miniaturized (intermediate) to terminal hairs and results in at least partial normalization of the hair follicle morphology. Minoxidil has no antiandrogen properties.3

While spironolactone and minoxidil are established monotherapies for FPHL, the different modes of action of these two therapies make it logical to combine these two agents. However, we are not aware of any reports of combination therapy in the literature. The additive regrowth seen in this woman with FPHL and biopsy proven androgenetic alopecia suggest that combination therapy should be considered for women presenting with FPHL.

References

1. MessengerA, De BerkerD, SinclairR. Disorders of hair. In: BurnsT, BreathnachS, CoxN, GriffithsC (eds). Rook’s Textbook of Dermatology, Vol. 1, 7th edn.
Oxford: Blackwell Science, 2004; 1–120.
2. YipL, SinclairR. Antiandrogen therapy for androgenetic alopecia. Expert Rev. Dermatol. 2006; 1: 261–9. CrossRef
3. MessengerAG, RundegenJ. Minoxidil: mechanisms of action on hair growth. Br. J. Dermatol. 2004; 150: 186–94. Synergy, Medline, ISI
4. MenardRH, GuenthnerTM, KonH, GilletteJR. Studies on the destruction of adrenal and testicular cytochrome P450 by spironolactone. J. Biol. Chem. 1979; 254: 1726–33. Medline, ISI
5. SinclairR, WewerinkeM, JolleyD. Treatment of female pattern hair loss with oral antiandrogens. Br. J. Dermatol. 2005; 152: 466–73.Synergy, Medline, ISI
6. LuckyAW, PiacquadioDJ, DitreCM, DunlapF, CantorI, PandyaAG, SavinRC, TharpMD. A randomized placebo-controlled trial of 5% and 2% topical minoxidil solutions in the treatment of female pattern hair loss. J. Am. Acad. Dermatol. 2004; 50: 541–53. CrossRef, Medline, ISI
 

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Br J Dermatol. 2005 Mar;152(3):466-73.Click here to read Links
Treatment of female pattern hair loss with oral antiandrogens.
Sinclair R, Wewerinke M, Jolley D.

University of Melbourne Department of Dermatology, St Vincent's Hospital, 41 Victoria Parade, Fitzroy 3065, Melbourne, Australia. [email protected]

BACKGROUND:
It has not been conclusively established that female pattern hair loss (FPHL) is either due to androgens or responsive to oral antiandrogen therapy.

OBJECTIVES:
To evaluate the efficacy of oral antiandrogen therapy in the management of women with FPHL using standardized photographic techniques (Canfield Scientific), and to identify clinical and histological parameters predictive of clinical response.

METHODS:
For this single-centre, before-after, open intervention study, 80 women aged between 12 and 79 years, with FPHL and biopsy-confirmed hair follicle miniaturization [terminal/vellus (T/V) hair ratio < or = 4 : 1] were photographed at baseline and again after receiving a minimum of 12 months of oral antiandrogen therapy. Forty women received spironolactone 200 mg daily and 40 women received cyproterone acetate, either 50 mg daily or 100 mg for 10 days per month if premenopausal. Women using topical minoxidil were excluded. Standardized photographs of the midfrontal and vertex scalp were taken with the head positioned in a stereotactic device. Images were evaluated by a panel of three clinicians experienced in the assessment of FPHL, blinded to patient details and treatment and using a three-point scale.

RESULTS:
As there was no significant difference in the results or the trend between spironolactone and cyproterone acetate the results were combined. Thirty-five (44%) women had hair regrowth, 35 (44%) had no clear change in hair density before and after treatment, and 10 (12%) experienced continuing hair loss during the treatment period. Ordinal logistic regression analysis to identify predictors of response revealed no influence of patient age, menopause status, serum ferritin, serum hormone levels, clinical stage (Ludwig) or histological parameters such as T/V ratio or fibrosis. The only significant predictor was midscalp clinical grade, with higher-scale values associated with a greater response (P = 0.013).

CONCLUSION:

Eighty-eight percent of women receiving oral antiandrogens could expect to see no progression of their FPHL or improvement. High midscalp clinical grade was the only predictor of response identified. A placebo-controlled study is required to compare this outcome to the natural history of FPHL.
 

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Recruitment for a womens Spironolactone hairloss trial is also being carried out at the University of British Columbia, Vancouver, British Columbia, Canada, V6G 1Y6.


Efficacy of Therapy With the Spironolactone Pills Compared to Minoxidil Lotion in Female Pattern Hair Loss
This study is currently recruiting participants.
Verified by University of British Columbia, September 2008

http://clinicaltrials.gov/ct2/show/NCT00175617?term=spironolactone+hair&rank=1
 

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Since April 2007 i take 50mg spironolactone with 1.25 of finasteride. I must say i'm happy with the results so far.
 
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