Plasma androgens in women with acne vulgaris

We have studied a group of young adult women of mean age 23.8 +/- 6.5 (SD) years with only acne (A, n = 46), only hirsutism (H, n = 10), and acne plus hirsutism (A + H, n = 19) who sought dermatologic care. We measured the androgens, total and free testosterone (T), free 17 beta-hydroxysteroids (17-beta), dehydroepiandrosterone sulfate (DS), and the androgen precursors 17 alpha-hydroxypregnenolone (17-Preg) and 17 alpha-hydroxyprogesterone (17-Prog), as well as testosterone-estrogen binding globulin in all patients. Plasma hormone levels of the patients were compared to those of 23 controls of mean age 25.6 +/- 6.6 years who had neither acne nor hirsutism. Mean levels of all hormones measured, except 17-Preg, were elevated in the women with acne. Fifty-two percent of Group A, 60% of Group H, and 63% of Group A + H patients had at least one abnormal hormone level. The most frequently elevated plasma androgens in all the women with acne were: free T 25%, free 17-beta 23%, and DS 19%. Total T was high in only 12%. Elevations of plasma androgens were present in some women who did not have hirsutism or irregular menses. Identification of endocrine abnormalities in women with acne may potentially offer an opportunity for hormonal therapy.     

Adrenal androgen abnormalities in women with late onset and persistent acne

Androgens are an essential prerequisite for the development of acne. The present study was undertaken to characterize the androgen status of women with late onset and persistent acne only and, using the dexamethasone (dex) suppression test, to identify the source(s) of the androgen excess. We measured serum levels of total testosterone (T), free testosterone (FT), androstenedione ( ⁴A), dihydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHEA-S) and sex hormone binding globulin (SHBG) in 34 healthy control subjects, in 34 women with mild acne and in 29 women with moderate or severe acne. Serum FT, DHT and DHEA-S levels in patients of both acne groups were significantly higher than those in the control subjects. The other hormone levels showed no significant differences between patients and control subjects, and there were no significant differences between the two acne groups in any of the androgen levels. In order to evaluate the ovarian and adrenal contributions to serum androgens in the acne patients, the serum levels of ⁴A, T, DHT and DHEA-S were measured prior to and following 2 weeks of dex therapy. Following the dex test, the DHT and T of adrenal origin were significantly higher in the acne patients than in the control subjects. These results suggest that, in acne patients, hyperandrogenaemia is likely to develop as a result of adrenal androgen excess. In addition, since abnormally high androgen levels are frequently seen in late onset and persistent acne, it seems that this condition is likely to be a sign of hyperandrogenism.     

The role of androgens in determining acne severity in adult women

BACKGROUND: Although many arguments have been put forth supporting the role of androgens in the aetiology of acne, their part in determining the severity of the disease is not well established. OBJECTIVES: The aim of our study was to evaluate the relationship between acne severity and the clinical and laboratory markers of androgenicity in a large group of patients. METHODS: Ninety women over 17 years of age with acne were enrolled into the study. The levels of testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulphate and sex hormone binding globulin (SHBG) were measured. Menstrual cycle regularity, hirsutism score, acne severity and ultrasound evaluation of polycystic ovaries were recorded. One-way analysis of variance, chi(2)-test and correlation analysis were used for data processing. RESULTS: Hirsutism was documented in 19 (21%) subjects, elevated levels of at least one androgen in 73 (81%) subjects, an irregular cycle was reported by 43 (48%) women, and polycystic ovaries were found in 45 (50%) women. The patients were divided into three groups according to acne severity. Acne was graded using the Leeds technique as minor in 43 (48%) cases, mild in 27 (30%) and moderate in 20 (22%). We did not demonstrate a positive correlation between the grade of acne severity and any of the clinical or laboratory markers of androgenicity assessed. On the contrary, women with a higher grade of acne severity showed lower values of the index of free testosterone, a lower hirsutism score and higher SHBG levels. CONCLUSIONS: Our study suggests that the severity of acne manifestation in adult women is not determined by androgen production.     

Correlation between endocrinological parameters and acne severity in adult women

Many studies demonstrate increased androgen levels and high prevalence of polycystic ovaries in women affected by acne. We evaluated the relationship between clinical features, ultrasonographic data on polycystic ovaries and hormonal parameters in 129 women >17 years of age with acne. Serum levels of androgens of ovarian and adrenal origin were measured. Menstrual cycle regularity, hirsutism, body mass index and ultrasonographic evaluation of ovaries were recorded. Raised levels of at least one androgen were evident in a majority of our patients. Only 19% of them had polycystic ovary syndrome. Hirsutism and acne severity correlated negatively with serum sex hormone-binding globulin (SHBG) levels (p<0.05). No correlation between acne severity and hirsutism was found. In post-pubertal women, severity of acne seems to depend on peripheral hyperandrogenism, with a negative relationship between the acne severity and serum SHBG levels. We strongly recommend the evaluation of serum SHBG levels in women with acne in order to select patients who can have a better response to appropriate hormonal regimes.     

IDIOPATHIC HIRSUTISM: CORRELATION OF SEVERITY OF HIRSUTISM WITH DEGREE OF HYPERANDROGENISM*

Abnormalities demonstrated in women with idiopathic hirsutism include elevated serum levels of various androgens, increased androgen production rates and decreased levels of sex hormone binding globulin (SHBG). In this study an attempt was made to correlate the severity of hirsutism (as graded by the method of Ferriman and Gallwey) with the levels of serum androgens and SHBG. In the group studied measurement of SHBG appeared to be a better index of the hyperandrogenic state than measurement of androgen levels themselves. Correlations were also made between the Ferriman and Gallwey subscores in the various body sites and the overall severity of hirsutism.     

Mild Insulin Resistance during Oral Glucose Tolerance Test (OGTT) in Women with Acne

The purpose of this study was to evaluate serum levels of basal insulin and glucose-stimulated insulin, and to evaluate their correlations with androgen levels in women with acne. Serum levels of total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and immunoreactive insulin (IRI) were measured and compared in thirty women with moderate or severe acne and thirteen healthy controls. Serum FT, DHT and DHEA-S levels in the acne group were significantly higher than those in the control group. In the acne group, there were no significant correlations between insulin or IGF-1 levels and T, FT, DHT and SHBG, despite the positive correlation between insulin and IGF-1. In order to determine the effects of insulin secretion as a dynamic response to an oral glucose tolerance test (OGTT) on serum androgen levels in acne patients, we examined the responses of serum insulin and androgen levels to a 75 g, 2 hour OGTT in the acne group and in the control group. Basal insulin levels were not significantly higher than those in the control group, but the summed insulin levels during the OGTT in the acne group were significantly higher than those in the control group. Serum T and FT levels in the acne group decreased during the OGTT, but these changes were not so significant when compared to normal controls. In conclusion, we tried to demonstrate mild insulin resistance during the OGTT in acne patients. However, postmeal transient hyperinsulinemia does not seem to play an important role in determining hyperandrogenemia in acne patients.     

Serum hormone levels in men with severe acne.

In order to evaluate the hormonal milieu in young men with severe acne, we measured serum estradiol (E2), total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), and sex hormone binding globulin (SHBG) levels in sixteen male patients aged 20-30 years with severe acne, including twelve cases of nodular-cystic acne, and in seventeen age-matched normal controls. There were no significant differences in the serum levels of T, FT, DHT, DHEA-S, or SHBG between the patients and the controls, but serum E2 was significantly higher in the patient population. Thus, the hemodynamics of serum androgens in male patients with acne do not seem to differ significantly from that of normal controls. Elevated E2 levels might affect the inflammatory response of acne vulgaris through the release of thymic hormones, as reported in the literature.     

Androgen status in women with late onset or persistent acne vulgaris

The androgen status of fifty women with persistent or late onset acne vulgaris has been investigated. Abnormalities of serum androgens and sex hormone binding globulin (SHBG) alone or in combination were present in 52% of the patients. Elevated serum testosterone and low SHBG were the commonest abnormalities found (46%). Raised levels of serum dehydroepiandrosterone (DHA) and DHA sulphate were present in 16% and 12% of patients respectively, but elevation of one or other of these androgens was the sole abnormality in only 6% of patients. Serum prolactin was raised in 18% of patients but there was no correlation between prolactin and androgen levels. There was also no correlation between the androgen levels and the severity, distribution or pattern of acne or the presence of hirsuties or irregular periods. The hormonal abnormalities found in this group of patients with acne are similar to those seen in females with the polycystic ovary syndrome and idiopathic hirsuties.     

The relationship of mild hirsutism or acne in women to androgens

The relationship in women between mild hirsutism or acne to androgen levels has not been well-defined. We investigated this in 62 Caucasian women, aged 18 to 21 years, by relating these pilosebaceous signs to plasma free testosterone (fT), the main circulating determinant of plasma androgenicity. Women with mild hirsutism (n = 13) had a significantly elevated fT (12.7 +/- 5.5, SD, pg/mL [44.1 +/- 19.1 pmol/L]) compared to normal controls (7.4 +/- 2.7 pg/mL [25.7 +/- 9.4 pmol/L]), as did subjects with minor acne (10.7 +/- 4.25 pg/mL [37.1 +/- 14.7 pmol/L]). The most important finding was the striking variability in the relationship between pilosebaceous overactivity and fT levels. In mildly hirsute subjects plasma fT was normal in half of the subjects, and the coefficient of variation of plasma fT was about twice what one would expect from individual variability. We could not demonstrate correlations among the variables of hirsutism, acne, and plasma fT. On the other hand, among 15 women with modest elevations of plasma fT levels (up to twofold), 27% had moderate hirsutism, 40% had mild hirsutism, and 33% had none. However, four of five of the latter patients (without hirsutism) had acne. The relationship of fT to acne severity varied similarly. To define the interactions between androgens and the pilosebaceous apparatus, we propose a model in which variation in apparent skin sensitivity and the level of androgen seem to contribute about equally to the pathogenesis of mild hirsutism and acne. The clinician should suspect that hyperandrogenemia will be found in about half the women with mild cases of hirsutism, and one third with minor acne.     

Androgen Status in Adolescent Women with Acne Vulgaris

Androgens are essential for the development of acne. The object of this study was to elucidate the androgen status of women with adolescent (Tanner's stage IV–V) acne alone and compare them to age-matched normal controls. We measured serum levels of total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), and dehydroepiandrosterone sulfate (DHEA-S) in 15 women with adolescent acne and 13 age-matched healthy controls. No significant differences were found between the mean levels of T, FT or DHT levels in patients and controls. However, the mean levels of DHEA-S in the patient population (1886 ± 829 ng/ml) were significantly (p<0.05) higher than normal controls (1287 ± 620 ng/ml). There was also no correlation between androgen levels and acne severity. Thus it is unlikely that serum androgens play a principal role in women with adolescent acne.     

Acne is not associated with abnormal plasma androgens

Plasma dehydroepiandrosterone sulphate, androstenedione, testosterone (T), dihydrotestosterone (DHT), and sex hormone binding globulin (SHBG) have been measured in 64 females and 26 males aged less than 25 years and with acne vulgaris. Oestradiol was measured in the males. Free T and free DHT were calculated. Acne was graded on three sites and the sebum excretion rate (SER) was measured in most patients. With the possible exception of free DHT, none of the plasma steroids or SHBG correlated with acne severity or with SER. Free DHT in the females showed a possible, but weak, correlation with total acne (r = 0.25, P = 0.07), but comparison with male data showed that this was not causative. The role of androgens in acne is permissive and plasma androgen measurements usually have no place in its management.     

Endocrine factors in pre- and postmenopausal women with hidradenitis suppurativa

The relationship between hidradenitis suppurativa (HS) and hyperandrogenism is largely based on the finding of an increased free androgen index due to a low sex hormone binding globulin (SHBG). As SHBG is now believed to be regulated by factors that influence body weight, and previous studies were not controlled for body weight, we have re-evaluated the androgen status of female patients with HS. We have studied the endocrine status of 66 women with HS. Twenty-three had acne, and 23 were significantly obese (body mass index: BMI >30). There was no relationship between obesity and disease duration. Nineteen of 56 women were hirsute. A premenstrual flare in disease activity was reported by 32 women, but this was not related to menstrual disturbances. No consistent relationship was reported with pregnancy. Eight women with HS were menopausal at presentation, and one developed her disease 6 years after the menopause. Plasma androgens in women with HS were compared with controls matched for BMI and hirsuties. There was no difference between HS and controls. Testosterone and dehydroepiandrosterone sulphate were normal in all subjects with HS. In obese subjects, SHBG was reduced, consistent with BMI-matched controls. We have found no supporting evidence for biochemical hyperandrogenism in women with HS when compared with age-, weight- and hirsuties-matched controls. We report the continuation and primary development of HS in postmenopausal women.     

Androgen excess in women with acne alone compared with women with acne and/or hirsutism

Acne is known to be one of the features of hyperandrogenism. The aim of the present work was to study women with persistent acne and without other evidence of hyperandrogenism, such as hirsutism, alopecia, or irregular menses. Among 87 female patients with acne and/or hirsutism, we defined three groups: group 1 (n = 29), patients having treatment-resistant acne without menstrual disturbance, alopecia, or hirsutism; group 2 (n = 27), patients with acne and hirsutism; and group 3 (n = 31), patients with hirsutism alone. Clinical chemistry criteria for hyperandrogenism were based on elevated values of one or more of the following parameters: plasma testosterone, delta-4-androstenedione, dehydroepiandrosterone, urinary 5 alpha-androstane 3 alpha-17 beta-diol, and 17-ketosteroids (with chromatography). Plasma and urine samples were drawn between the 18th and 25th days of the cycle. Among group 1 patients, we found 25 subjects (86%) with hyperandrogenism, according to these laboratory criteria. The etiologies were: polycystic ovary syndrome (36%), adrenal hypersecretion (40%, of which 12% showed secondary polycystic ovaries), isolated increase in 5 alpha-androstane 3 alpha-17 beta-diol (20%), and hyperandrogenism without diagnosis (4%). The parameters were found to be more elevated in these patients than in a control group of 30 normal volunteer women. In groups 2 and 3, the findings were essentially the same as in group 1, except for increased levels of testosterone and the testosterone/SHBG ratio. Furthermore, it was evident that persistent acne may be an isolated sign of hyperandrogenism.     

Pituitary function and DHEA-S in male acne and DHEA-S, prolactin and cortisol before and after oral contraceptive treatment in female acne

Pituitary function (TRH-LHRH stimulation test) was investigated in male acne patients and serum levels of dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and other biochemical parameters were investigated in male acne patients and in female acne patients before and after treatment with an oral contraceptive. The TRH-LHRH stimulation test was performed with 15 male patients suffering from severe cystic acne and 7 healthy volunteers. Basal and stimulated prolactin, LH and FSH levels were statistically similar in the patients and control groups. However, the stimulated LH levels of the patients were 60% higher than those in controls. SHBG levels were significantly) higher in the patient group compared to those in the control group. Thirty-three female acne patients were randomly divided into two groups and treated for six months with an oral contraceptive containing 0.030 mg ethinylestradiol (EE) plus 0.150 mg levonorgestrel or 0.150 mg levonorgestrel. After six months' treatment a 30% decrease in DHEA-S levels were observed in the desogestrel/EE group and a 15% decrease in the levonorgestrel/EE group; the difference was not statistically significant. At the same time serum total cortisol increased by 75-100% and free testosterone fell by 30-40% in both groups, whereas SHBG elevated 250% in the desogestrel/EE group and 30% in the levonorgestrel/EE group. Acne improved significantly in both groups, desogestrel/EE showing greater improvement. A decrease in SHBG and increase in DHEA-S levels appear to be the most common hormonal changes in acne. Oral contraceptive treatment induces an increase in SHBG and decrease in DHEA-S and also improves acne.     

Hormonal Profiles and Prevalence of Polycystic Ovary Syndrome in Women with Acne

One of the important etiologic factors in acne is an increase in sebaceous gland activity, which is androgen dependent. Acne is a common manifestation of hyperandrogenemia. Therefore, acne may not only cause cosmetic concern but may also be a sign of underlying disease. In females, the most common cause of hyperandrogenemia is polycystic ovary syndrome (PCOS). The purpose of this study was to determine the hormonal profiles of women with acne and the prevalence of PCOS in women attending the dermatological clinic with acne problems. The diagnostic criteria of PCOS were clinical findings of menstrual disturbances and hyperandrogenism (acne, seborrhea, hirsutism), pelvic ultrasound imaging of PCO (multiple subcapsular ovarian cysts 2–8 mm. in diameter, with dense echogenic stroma), and an elevated luteinizing hormone (LH) to follicle stimulating hormone (FSH) ratio. There were 51 women with acne; 20 regularly menstruating volunteers without acne served as a control group. PCOS was found in 19 out of 51 patients with acne (37.3%) and none of the control group. Twenty acne patients had abnormal menstruation (39.2%). Acne cases had higher mean levels of serum total testosterone (T), free T, dehydroepiandrosterone sulfate (DHEAS) and prolactin (PRL). No statistically significant difference was observed for LH, FSH or sex hormone binding globulin (SHBG). Because of this high prevalence of PCOS in women with acne, all women presenting with acne should be asked about their menstrual pattern and examined for other signs of hyperandrogenemia. Hormonal profile determination as well as pelvic ultrasonography for ovarian visualization should be performed to confirm the diagnosis of PCOS in female acne patients who have menstrual disturbances.     

Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women

OBJECTIVES: To determine if insulin-like growth factor 1 (IGF-1) and androgen levels (1) correlate with the presence and severity of acne in adult men and women, and (2) correlate directly with each other and interact in affecting acne. DESIGN: Case-control study and single-center examination of hormone levels in a cohort of volunteers. SETTING: Academic referral center. PATIENTS: Thirty-four subjects (8 women and 8 men with clinical acne, 10 women and 8 men without clinical acne). Clinical acne is defined by a history of persistent acne (acne present on most days for several years), recent acne treatment, and the presence of 10 or more inflammatory acne lesions and 15 or more comedones. INTERVENTIONS: Single visit for serum sampling. MAIN OUTCOME MEASURES: Serum levels of IGF-1 and androgens were determined, adjusted for age, and compared based on the presence or absence of clinical acne using an analysis of covariance. Correlations between hormone levels and acne lesion counts were calculated within each subgroup. Correlations were also calculated between serum levels of IGF-1 and androgens. Further statistical testing was conducted to determine whether IGF-1 or androgens had a greater effect on acne lesion counts. RESULTS: Dehydroepiandrosterone (DHEAS), dihydrotestosterone (DHT), and IGF-1 correlated positively with acne lesion counts in women. Androstenedione and DHEAS correlated with acne lesion counts in men. Although the age-adjusted mean serum levels of IGF-1 were higher in women with clinical acne than in women without clinical acne, this difference did not achieve statistical significance. No difference in IGF-1 level was noted in men based on the presence of clinical acne. In women with clinical acne, IGF-1 correlated with DHT. In men with clinical acne, IGF-1 correlated with DHEAS and androstenedione. In men and women with clinical acne, the effects of androgens on increased acne lesion counts were dependent on the influence of IGF-1. CONCLUSIONS: Increased IGF-1 levels in addition to androgens may influence acne in adult men and women. While IGF-1 appears to have a stronger effect on acne in women, androgens may play a greater role in acne for men. However, in both men and women these hormones are interrelated, possibly owing to reciprocal effects on hormone production.     

Acne: effect of hormones on pathogenesis and management

In the pathogenesis of acne, androgen hormones play a crucial role. In the treatment of acne, hormonal therapies provide valuable alternatives to standard modalities in selected women. Although numerous factors contribute to the development of acne, the requirement for androgens is absolute and is one that allows for effective treatments in women through inhibition of androgen expression. The two prerequisites for androgen expression at the level of the pilosebaceous unit are the presence of androgen in the form of either testosterone or dihydrotestosterone; and functioning androgen receptors. A third component may be the metabolism of androgen precursors to active androgens within pilosebaceous units. Hormonal treatment of hyperandrogenism (acne, hirsutism, androgenetic alopecia) such as that seen in polycystic ovary syndrome, centers on reduction of circulating androgen levels and androgen receptor blockade. Combination oral contraceptives represent the primary treatment modality for reducing circulating androgens from ovarian and, to a lesser degree, adrenal sources. Newer formulations may also have clinically significant androgen receptor blocking and 5alpha-reductase inhibiting effects. Newer oral contraceptives have high safety profiles and are used widely internationally for this purpose. Androgen receptor blockers currently in use include spironolactone, cyproterone acetate, and flutamide. Androgen receptor blockers are frequently combined with oral contraceptives to achieve optimal results in selected women. In women with adrenal hyperplasia, low-dose corticosteroids may be added to reduce adrenal androgen precursors. Inhibition of enzymes of androgen metabolism in the pilosebaceous unit remain largely investigational in the treatment of acne, although the benefit of 5alpha-reductase (type 2) inhibition is established in androgenetic alopecia in men. This article reviews the essentials of hormonal influence in acne pathogenesis, discusses the hormonal therapies most utilized in the treatment of acne, and the pre-treatment evaluation of women in whom hormonal therapies are being considered.     

Oral contraceptives in the treatment of acne

Oral contraceptives (OCs) can reduce acne by lowering the production of adrenal and ovarian androgens, by inhibiting 5-alpha-reductase, which in turn, reduces the levels of dihydrotestosterone, and by stimulating sex hormone binding globulin (SHBG), thus reducing the levels of free testosterone. In newer OCs, such as Tricyclen and Diane-35, the progestin component is minimally androgenic and anti-androgenic respectively, thereby enhancing the favorable profile of these products in the treatment of hyperandrogenic disorders, including acne. The efficacy of these agents and their long-term safety profile supports their use in various grades of acne in females: * As adjunctive therapy to topical agents for women with mild non-scarring acne desiring oral contraception * As primary therapy for patients with moderate non-scarring acne in combination with topical therapy and systemic antibiotics * As one of two preferred methods of contraception in patients with scarring and severe inflammatory acne being treated with systemic isotretinoin.     

Low dose prednisolone or oestrogen in the treatment of women with late onset or persistent acne vulgaris

Women with persistent or late onset acne vulgaris were divided into two treatment groups. The first received continuous low dose prednisolone to suppress ACTH-dependent androgen secretion and the second was treated with cyclical oestrogens with medroxyprogesterone to elevate sex hormone binding globulin (SHBG). In both groups there was a significant improvement in the severity of the acne after 4 months’treatment. Although pre-existing hormonal abnormalities were corrected, the improvement in the acne did not correlate with the baseline hormone levels. However, suitable oestrogen-progesterone combinations or low dose prednisolone may be given, alone or in combination, to suppress free circulating androgens in these patients with a high probability of improving their acne.     

Normalized androgen ratio: its application to clinical dermatology

It is generally accepted that the biological activity of androgens is a function of their free (non-protein bound) concentration. The free androgen concentration is determined by the relative concentrations of total androgens and the proteins to which they bind. It can be expressed as a normalized androgen ratio (NAR). Total serum androgen concentration (TSA) and NAR have been estimated in a series of 114 patients with acne vulgaris, hirsutism or androgenetic alopecia. Hormone therapy has been instituted in a proportion of the cases using the TSA and NAR values as the determinant of the treatment regime. Gilliland, Smeaton & Rowland (1978) have described a simple, rapid and inexpensive method of determining an index of free (unbound) serum androgen (17β-OH steroid) concentration. It is expressed as a normalized androgen ratio (NAR). They demonstrated a raised NAR in 42% of a series of ninety-nine hirsute females. Of these, 50% showed raised total serum 17β-OH steroid concentration with normal testosterone-estradiol-binding-globulin (TEBG) activity, while 43% had normal total 17β-OH steroid concentration with decreased TEBG activity. As the biological activity of androgens depends on free (unbound) 17β-OH steroid concentration, it would seem likely that the estimation of NAR could be useful in cases of acne vulgaris, hirsutism and androgenetic alopecia where excess androgen activity can be reasonably expected. Over a period of 18 months, total serum androgen (TSA) and NAR estimations have been determined in a series of 114 female patients suffering from acne vulgaris (sixty-four), hirsutism (thirty-two) and androgenetic alopecia (eighteen). Raised NAR values were found in 16%, 31% and 42% of the patients respectively. The patients in this series were referred for biochemical analysis where clinical assessment suggested that a knowledge of androgen activity could be helpful in the management of their case.