Although  the androgen dependency of the sebaceous gland is  noncontroversial, the precise reason  for the seborrhoea characteristic  of acne  is not at all clear. There are many reasons:

1 Few investigators are interested in this problem.

2 Biopsies are usually required to investigate the end  organ response.

3 The pilosebaceous unit has to be separated  from other androgen-responsive tissues to obtain the ideal  data.

4 Multiple metabolites must be investigated.

5 In the plasma there are many hormones which can be investigated. It is preferable to  measure free, i.e. biologically available hormones, but there may be a gradation  of  biological  activity  between free and bound hormones and this is difficult to measure. Thus there are three fundamental approaches. 

Ideally, one should investigate plasma levels of the sex  hormones, investigate the end-organ  response and look at both parameters together.

 

  A survey of the literature over the last fifteen years would suggest to the uncritical  observer  that many female acne patients have abnormal levels of circulating hormones, but many of these reports can be criticised. This author has attempted to analyse twenty-two papers where levels of circulating hormones have been investigated.10"31 Ideally, such studies should have adequate controls, state precisely the presence or absence of other androgenic  features (such  as  hirsuties or irregular periods) and relate the findings to acne severity. These facts are  summarized  in Table 9.2. Not all  papers contain all the pertinent facts and thus the denominator in this Table does not add  up to twenty-two - the number of papers reviewed.

 

  Only nine had adequate controls. In eleven papers it was  not  possible to  know  whether the subjects were hirsute or had menstrual problems. In four papers over 25 per cent of the subjects were excessively hairy and in seven over 25 per cent had abnormal periods. In two papers the subjects had other gynaecological problems; in one of these two papers the patients' primary referral was to an infertility clinic.

 

   The peak age of acne severity is 17-20 years and yet in fourteen of these papers the mean age of the females investigated was over twenty years.

 

   Eighteen  of  the twenty-two investigations  showed one (6/21) or more (12/21) abnormalities in the hormones, but only in two was a correlation found between acne severity and the hormonal changes. In one report correlation existed between acne severity and free testosterone and free DHT. In the other report there was a correlation between  acne and  a low SHBG  (i.e. an increased  free  testosterone).  Four authors  found no increase in the  sex hormones; in three of these reports the patients  were not hairy, nor did they have  any significant menstrual problems and the  mean  age was less than  twenty  years. Such data were not recorded adequately in the fourth paper. Of four  studies reviewed which related acne in males to the level of sex hormones, only one  abnormality was found  by  one group. Palatsi  et  al23 reported a significantly  lower SHBG in the acne patients; this will represent effectively a high free testosterone.  However, it is important to note that the control patients in this study were older (mean age 24.1 ±  7.9 years) than the acne  patients (mean age  19.7 ± 7.5 years), who all had cystic acne. Age does affect sex  hormone levels.

 

   Many practitioners and  patients with acne believe that stress exacerbates the condition. Since adrenocorticotropic hormone (ACTH) is produced in response to stress, some researchers have focused on its  possible role in the  development of acne. Meinhof et al studied sixteen  patients with abnormal  menstrual  cycles and acne  and  observed hyperresponsiveness  to  ACTH administration.32  Rose  et  al noted  abnormally high urinary concentrations of pregnanetriol or tetrahydro-S after ACTH infusion in seven of eleven women with persistent treatment-resistant acne.33 Rose  also found partial  11-  or  21-hydroxylase deficiencies  in twenty women with severe  acne, hirsutism, abnormal menses and infertility.  Chrousos et al were unable  to  confirm these findings in a study of a small group of women with acne.20 Thus, perhaps adrenal gland dysfunction plays a role  in some patients with acne, particularly when there is associated  hirsutism, abnormal menses  and infertility.

 

  Rose et al investigated eleven women with chronic nodulocystic acne. They were subjected to a twentyfour hour infusion of ACTH and their urine analysed for  tetrahydro-S  and  pregnanetriol and  the  results obtained compared  to those found in eight  control women.33 Seven of the  acne patients exhibited elevated excretion of either one or the other, probably indicative of those patients having a partial 11- or 21-hydroxylase deficiency, respectively.

 

  Lookingbill  et  al  found  that  the  plasma  3aandrostanediol  glucuronide  value  was elevated in thirteen of eighteen  patients with acne, with a mean value for the entire group nearly three times that of the normal controls (117ng/dl against 43ng/dl).27  In this study  the  mean  plasma   levels of  the  precursor androgens were similar to levels in a group of carefully selected  acne-free   and  hirsuties-free  age-matched female controls. These reports support the concept that target  tissue androgen  production plays an important hormonal role in the pathogenesis of acne in women and that plasma 3a-DIOL G may be a sensitive marker of this process .27  Furthermore,  men have significantly higher  levels of free  testosterone and free DHT compared to females, and not all men have acne.

 

  In no paper was there any measurement of sebaceous gland activity.  Thus, from  this critique, this author cannot accept that in most 'average' acne patients the acne is  due to  an increased level of  circulating hormones.  There is  a need to  study the 'average' acne patient and relate their acne severity and age of onset of acne to SER, the plasma hormone  profiles  and the end-organ response of the gland.