The presence of the 21-hydroxylase deficiency carrier status in hirsute women: phenotype-genotype correlations.

OBJECTIVE: To determine the role of heterozygosity for mutations in the 21-hydroxylase gene (CYP21) in the pathogenesis of hyperandrogenism. DESIGN: Controlled clinical study. SETTING: Tertiary care institutional hospital. PATIENT(S): Forty hirsute women and 13 healthy control women. INTERVENTION(S): The source of androgen excess was determined by the changes in serum testosterone levels in response to a single 3.75-mg i.m. dose of triptorelin. MAIN OUTCOME MEASURE(S): CYP21 molecular genetic analysis and serum 17-hydroxyprogesterone levels. RESULT(S): Eight patients and one control were heterozygous carriers of CYP21 mutations. Two patients with adrenal hyperandrogenism and one patient with ovarian hyperandrogenism, who carried the V281L mutation had an increased ACTH-stimulated 17-hydroxyprogesterone level (>4.1 ng/mL) that persisted during gonadal suppression. Another patient with adrenal hyperandrogenism carried the V281L mutation, and her ACTH-stimulated 17-hydroxyprogesterone level was elevated only during gonadal suppression. Four patients (three with idiopathic hirsutism, one with ovarian hyperandrogenism) and one control were carriers of CYP21 mutations typically associated with classic congenital adrenal hyperplasia but had normal basal and ACTH-stimulated 17-hydroxyprogesterone levels. Nine patients without CYP21 mutations had increased ACTH-stimulated 17-hydroxyprogesterone levels; these decreased to normal in six of the patients during gonadal suppression. CONCLUSION(S): The response of serum 17-hydroxyprogesterone to ACTH does not predict CYP21 carrier status. No clear concordance was found between the CYP21 genotype and the functional origin of androgen excess.     

Long-term remission of ovarian hyperandrogenism after short-term treatment with a gonadotropin-releasing hormone agonist

OBJECTIVE: To assess the long-term effects of GnRH agonist (GnRH-a) therapy in a patient with benign ovarian hyperandrogenism. DESIGN: Case report. SETTING: University Hospital endocrine outpatient's clinic. PATIENT(S): A 55-year-old postmenopausal woman with hirsutism and virilization of ovarian origin. INTERVENTION(S): Treatment with a course of GnRH-a (triptorelin 3.75 mg IM every 28 days for 4 months). Follow-up for 3 years. MAIN OUTCOME MEASURE(S): Serum gonadotropin and androgen levels, clinical assessment using the Ferriman-Gallwey score, and assessment of ovarian morphology by ultrasonography. RESULT(S): Administration of triptorelin resulted in suppression of serum testosterone and gonadotropin values and relief of the hyperandrogenic symptoms. Upon discontinuation of treatment, the patient's serum gonadotropin levels returned to the postmenopausal range, but the testosterone levels remained normal and the patient was asymptomatic for an observation period of 3 years. CONCLUSION(S): This case is the first example of long-term remission of ovarian hyperandrogenism in a postmenopausal woman, after short-term treatment with GnRH-a. This supports the view that GnRH-a therapy could be used, even in short courses, for the long-term suppression of benign ovarian hyperandrogenism.     

Role of the pentanucleotide (tttta)(n) polymorphism in the promoter of the CYP11a gene in the pathogenesis of hirsutism

OBJECTIVE: To determine if the (tttta)(n) repeat polymorphism in the promoter region of CYP11a gene is associated with hirsutism and hyperandrogenism in women from Spain. DESIGN: Controlled clinical study. SETTING: Tertiary-care institutional hospital. PATIENT(S): Ninety-two hirsute women and 33 healthy control women. INTERVENTION(S): Basal and adrenocorticotropin-stimulated serum samples and genomic DNA extracted and purified from whole-blood samples were obtained during the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): CYP11a (tttta)(n) repeat-polymorphism genotype and serum ovarian and adrenal androgen levels. RESULT(S): None of the CYP11a (tttta)(n) polymorphic alleles was associated with hirsutism. The absence of the four-repeat-units allele (4R-- genotype), which has been reported by other authors to be associated with polycystic ovary syndrome (PCOS), was found in 22.4% of the women studied here and was equally distributed among patients and controls, independently of the presence of PCOS and/or ovarian or adrenal hyperandrogenism. No differences were observed in serum hormone concentrations in 4R-- individuals as compared with subjects with at least one four-repeat-units allele. CONCLUSION(S): The (tttta)(n) repeat polymorphism in the promoter region of CYP11a does not appear to play any significant role in the pathogenesis of hirsutism and hyperandrogenism in women from Spain.     

Treatment of severe hirsutism resulting from hyperandrogenism with the reverse sequential cyproterone acetate regimen

Women with severe hirsutism resulting from hyperandrogenism often respond poorly to suppressive therapy aimed at decreasing adrenal or ovarian androgen production. Antiandrogens, such as cyproterone acetate, prevent androgens from expressing their activity at target sites by inhibiting the formation of the androgen/cytosol binding protein complex. Seven severely hirsute hyperandrogenic women were treated for six months with the reverse sequential cyproterone acetate regimen. Pretreatment plasma testosterone (T) levels were elevated in all subjects, and sex hormone binding globulin (SHBG) binding capacity was depressed. A free testosterone index, as assessed by the T/SHBG ratio, was markedly elevated. A marked and significant decrease in T levels and the T/SHBG ratio occurred during the first two cycles of treatment (p less than 0.01). Hirsutism grading assessed by the semiquantitative method of Ferriman and Gallwey did not change significantly until four months after the beginning of therapy but improved by six months of treatment. There was a marked antigonadotropic effect in terms of suppression of LH and FSH. The reverse sequential cyproterone acetate regimen produces rapid normalization of the plasma T, SHBG and free testosterone index, but resolution of the hirsutism is slower and requires several months of therapy.     

β-Endorphin basal levels in hirsute women

The basal levels of β-endorphin were measured in 43 women with various grades of hirsutism. The degree of the hair growth, weight, body mass index (BMI), age, menstrual regularity and various androgen or pituitary hormone values were not sufficient to distinguish the patients with regard to their β-endorphin levels. In 11 patients a clinical diagnosis of a polycystic ovarian disease-like disorder was made. The β-endorphin values of these women did not differ from those of 10 women with adrenal hyperandrogenism or the other hirsute women with identical BMI. Plasma β-endorphin was significantly higher in obese hirsute patients with a low testosterone/sex-hormone-binding globulin (T/SHBG) ratio than in lean, nonhirsute women with a higher T/SHBG ratio (P < 0.02). The findings suggest a possible but complex connection of β-endorphin with some forms of female hyperandrogenism.     

Evidence for adrenal and/or ovarian dysfunction as a possible etiology of idiopathic hirsutism

Thirty-one cases of idiopathic hirsutism, characterized biochemically in the basal state by increased levels of urinary 3 alpha-androstane-5 alpha, 17 beta-diol and normal levels of the main androgens, were studied. In order to determine a possible etiologic heterogeneity of idiopathic hirsutism, pituitary gonadotropin responses to synthetic luteinizing-releasing hormone (LRH) and adrenal steroid responses to adrenocorticotropic hormone (ACTH) stimulation were evaluated and the results were compared to those in six normal women. On the basis of the results obtained in each hirsute patient after LRH and ACTH tests, two groups were identified. The majority, 23 of 31 hirsute patients (group I), had results similar to those in the control group. In the other eight patients (group II), biologic abnormalities were disclosed and suggested a partial adrenal 11 beta-hydroxylase defect in two patients, an incomplete form of adrenal 3 beta-ol deficiency in one patient, an adrenal hyperreactivity without evident cause in two patients, and polycystic ovary syndrome in association with an adrenal hyperreactivity in three patients. As a group, the eight patients showed ACTH-stimulated increments in testosterone, delta 4-androstenedione, dehydroepiandrosterone, and 17-ketosteroids that were significantly greater (p less than 0.01) than the mean responses in the control group. The conclusion is that some women who previously were designated as having "idiopathic" hirsutism had an adrenal and/or ovarian component to their hyperandrogenism which could be shown only by appropriate dynamic tests.     

11 beta-hydroxyandrostenedione: a marker of adrenal function in hirsutism

To assess the role of the adrenal glands in the development of hirsutism, levels of 11 beta-hydroxyandrostenedione (11 beta-OHA), 17 alpha-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulphate (DHEAS), androstenedione (delta 4A), and free and total testosterone (T) were measured in 63 hirsute females and 30 control patients. Six of the hirsute patients had basal levels of 11 beta-OHA and 17-OHP and responses to adrenocorticotropic hormone that were significantly greater than these values in controls and the other hirsute women. These women were designated as having an adrenal source for their hirsutism. Women with polycystic ovarian syndrome and idiopathic hirsutism had normal values of 11 beta-OHA and 17-OHP. Levels of total and free T, DHEAS and delta 4A were significantly higher than control values in all of the hirsute women. This study demonstrates that 11 beta-OHA can be used as a marker to assess the adrenal contribution to hirsutism.     

Effect of dexamethasone on serum cortisol and androgen levels in hirsute patients.

The serum levels of the following steroids were measured in 59 hirsute patients before (control) and after (post-dexamethasone) administration of dexamethasone (Dex) for 7 days: cortisol (F), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), androstenedione (A), testosterone (T), and 5alpha-dihydrotestosterone (DHT). Assuming that Dex-suppressibility implied adrenal origin, the source of excess androgens was also evaluated. All patients showed elevated level of only one androgen: 4 had elevated DHEA-S; 4 had elevated T; 3 had elevated DHT. No patient had an elevated DHEA or A without an evelation of the other androgens. The control levels of DHEA-S were above normal in 45 patients; the DHT levels were elevated in 43 patients; 31 patients had elevated T levels; and 25 patients elevated A; and 24 patients, DHEA levels. In 32 patients with adequate suppression of adrenal androgens after 7 days of Dex administration, the source of excess androgens could be evaluated. Of 13 patients with elevated A levls, the excess A production was of adrenal origin in 6 cases, of ovarian origin in 5 cases, and of mixed origin in 2 cases. Of 15 patients with elevated T levels, the excess T production was of adrenal origin in 3 cases, of ovarian origin in 10 cases, and of mixed origin in the remaining 2 cases. Of 25 patients with elevated DHT levels, the excess DHT production was of adrenal origin in 16 patients, of ovarian origin in 5 patients, and of mixed origin in 4 patients. Of the 32 patients with an adequate Dex suppression test, 14 showed evidence of adrenal hyperandrogenism, 5 had ovarian hyperandrogenism, and mixed hyperandrogenism was present in the remaining 13 patients. There was an adrenal source of hyperandrogenism in 27 of 32 patients (14 pure adrenal and 13 mixed adrenal-ovarian), which represents 85% of the 32 patients.     

Adrenal corticoid hyperresponsiveness in hirsute women

Data are limited on the existence of adrenal hyperplasia or cortisol oversecretion in women with hirsutism. Supranormal responses of cortisol (greater than 20 micrograms/dl) were observed at 15 and 30 minutes after the 8:00 A.M. adrenocorticotropin (0.5 U) injection (performed after 1 mg of dexamethasone taken orally at midnight) in 6 of the 12 hirsute women (hirsute I) and in all 4 women with Cushing's disease. Baseline plasma levels of corticoids, androgens, and gonadotropins, body weight, menstrual history, and degree of hirsutism were all indistinguishable between the two hirsute groups. The mean plasma levels of cortisol and 17-hydroxyprogesterone were both significantly greater in the hirsute I group and in those with adrenal hyperplasia caused by Cushing's disease than in normal subjects. Our data indicate that adrenal hyperplasia is a common abnormality in women with hirsutism. We speculate that this abnormality may contribute to the pathogenesis of hirsutism and ovarian dysfunction in many hirsute women.     

Ovarian hyperandrogenism in adolescent girls with menstrual disorders

OBJECTIVES: In women with polycystic ovaries (PCO) hyperandrogenemia, an increased LH-concentration and a hightened ratio of LH/FSH are common. In adolescent hirsute girls with menstrual disorder, which may herald PCO in adulthood, ovarian hyperandrogenemia was under scrutiny. In most of them functional ovarian hyperandrogenism (FOH) is present in response to challenge with GnRH analog. It is not known whether FOH is involved in the pathogenesis of menstrual disorders in adolescent girls without hirsutism. MATERIAL AND METHODS: 24 girls with menstrual disorder in the mean age of 17.5 +/- 1.6 years old were investigated and compared to the age matched group of girls with regular menses. Basal and GnRH stimulated levels of ovarian androgens and gonadotropins were measured and USG of the ovaries were performed in all girls. RESULTS: In over 50% of girls with menstrual disorder basal and stimulated 17 OH progesteron and androstenedione levels were found significantly higher as compared to the control groups. In all girls but three they were not associated with the polycystic structure of the ovaries. Only half of these girls had an increased LH/FSH ratio. CONCLUSIONS: Functional ovarian hyperandrogenism may be present in adolescent girls with menstrual disorder in spite of the absence of the clinical signs of hirsutism and polycystic structure of the ovaries.     

The Addition of Dexamethasone to Antiandrogen Therapy for Hirsutism Prolongs the Duration of Remission

Objective: To determine whether the addition of dexamethasone to antiandrogen therapy prolongs the duration of remission in women with hirsutism.

Design: Follow-up study of patients treated with one of four regimens: spironolactone (100 mg/d) for 1 year, dexamethasone (0.37 mg/d) for 1 year, dexamethasone (0.37 mg/d) plus spironolactone (100 mg/d) for 1 year, or dexamethasone (0.37 mg/d) plus spironolactone (100 mg/d) for 2 years.

Setting: Academic medical practice in reproductive endocrinology.

Patient(s): Fifty-four women with hirsutism and hyperandrogenism.

Intervention(s): Ferriman-Gallwey-Lorenzo scores were obtained and serum levels of testosterone, unbound testosterone, and dehydroepiandrosterone sulfate were measured before therapy, every 6 months during therapy, and for 1 year after the withdrawal of therapy.

Main Outcome Measure(s): Hirsutism scores and serum indices of hormonal changes were monitored.

Result(s): Ferriman-Gallwey-Lorenzo scores and androgen levels remained low 1 year after the withdrawal of therapy in patients who were treated with dexamethasone, either alone or in combination with spironolactone. In patients who were treated with spironolactone alone, hirsutism scores had returned to baseline values after 1 year.

Conclusion(s): The addition of an agent that suppresses androgen levels may be useful to prolong the duration of remission of hirsutism in women with hyperandrogenism who are treated with antiandrogens.     

A practical dexamethasone suppression test to evaluate hirsute women

Fifty five hirsute women were subjected to a 2-week dexamethasone (DXM) suppression test. The pre- and post-DXM plasma dehydroepiandrosterone-sulfate (DS) and testosterone (T) were measured by radioimmunoassay to define the source of androgen excess in hirsute women. Four patients (7%) failed to have adequate adrenal suppression due to failure in medication. Among the 51 patients with adequate adrenal suppression, the source of androgen excess was clearly defined in 48 patients (94%). Seventeen patients (33%) showed ovarian source, 13 patients (26%) had adrenal source, while 18 patients (35%) revealed a mixed adrenal and ovarian source. Normal baseline DS and T levels were noted in 22% of hirsute women and more than half (55%) of them had ovarian androgen excess. Even in 17 patients with normal DS and elevated T, 6 patients (36%) suggested adrenal androgen excess. The source of androgen excess in hirsute women seems evenly distributed among the ovarian, the adrenal, and the mixed group.     

Serum levels of prostate-specific antigen and androgens after nasal administration of a gonadotropin releasing hormone-agonist in hirsute women.

We aimed to determine whether ovarian suppression affects the production rate of prostate-specific antigen (PSA) in hirsute women. A total of 34 hirsute women who had a modified Ferriman-Gallwey (FG) score of > or = 7 and 14, non-hirsute women as the control group were recruited for this prospective controlled study. Serum samples for evaluation of basal hormones and PSA concentration were collected and were analyzed by commercial kits and chemiluminescent enzyme immunoassay. The hirsute women were given 400 microg/day nafarelin acetate for 3 months. Basal hormones, PSA levels and FG scores were then assessed. ANOVA and Tukey test were used to compare differences in means between the hirsute and the non-hirsute group at the beginning of the study. Student's t test, Tukey test and repeated measures variance analysis were used to evaluate differences in the study group and between the women with polycystic ovary syndrome (PCOS) and idiopathic hirsutism after gonadotropin releasing hormone (GnRH)-agonist administration. Statistical significance was assumed with a value of p < 0.05. PCOS and idiopathic hirsutism were diagnosed in 58.8% and 41.2% of 34 hirsute women, respectively. Age and body mass index (BMI) were similar in the hirsute and the control group (p > 0.05). FG scores in the PCOS group (20.3 +/- 1.7) were statistically similar to those of the group with idiopathic hirsutism (17.6 +/- 1.7) (p > 0.05). The non-hirsute women had significantly lower serum PSA concentrations than the hirsute group (p < 0.001).The basal mean level of PSA was 0.095 +/- 0.001 in the PCOS, 0.0061 +/- 0.009 in the idiopathic hirsute and 0.0040 +/- 0.004 ng/ml in the control group. No significant difference in the mean PSA levels was noted between the PCOS and the idiopathic hirsute subgroups before and after GnRH agonist treatment (0.0096 +/- 0.01 and 0.0051 +/- 0.032 ng/ml, respectively) (p > 0.05). FG scores, testosterone, 17alpha-hydroxyprogesterone and dehydroepiandrosterone sulfate levels were significantly decreased in the hirsute group following treatment (p < 0.001). PSA levels in hirsute women were higher than in non-hirsute women and independent of BMI, age and androgen deprivation. PSA concentration may be mediated through extragonadal sites and possibly through a long-standing hyperandrogenemic environment such as in PCOS and idiopathic hirsutism. Further investigation as to the significance of PSA in women with hirsutism and whether antiandrogens directly act to inhibit biosynthesis of PSA is warranted.     

Plasma androgens,progestins, and prolactin in hirsutism

Blood samples were obtained from 158 hirsute women for determination of dehydroepiandrosterone-sulfate (DS), testosterone (T), progesterone (P), 17α-hydroxy-progesterone (17P) and prolactin (PRL). The percent frequency of elevated level of these hormones in hirsute women was: DS: 35%, T: 55%, P: 25%, 17P: 53% and PRL: 6%. The mean (± SE) levels of DS (2.36 ± 0.1 μg/ml) and T (714 ± 21 pg/ml) in hirsute women were elevated, both in the pre- and postovulatory phases; while 17P in hirsute women was decreased in the postovulatory phase (1.59 ± 0.48 ng/ml) and increased in the preovulatory phase (1.51 ± 0.18 ng/ml) when they were compared with their respective controls. PRL in postovulatory hirsute women was also lower (12.0 ± 1.1 ng/ml) than the control. Sixty patients were subjected to a 2-wk dexamethasone (DXM) suppression test to determine the source of androgen excess. The results of DXM suppression test suggested that the sources of androgen excess in hirsute women were: ovarian: 33%, adrenal: 25%, mixed (ovarian plus adrenal): 35%, and none: 7%. The results also suggested that excess progestins in hirsute women were attributed to either ovarian (P) or adrenal (17P) hypersecretion. Correlation analysis between these hormones showed a significant (P < 0.05) correlation only between P vs. 17P, T vs. 17P, and T vs. DS.     

Prolactin modulates peripheral androgen metabolism

Although hyperprolactinemia may be associated with hyperandrogenism, if hirsutism develops, it is usually a mild form. This study was designed to investigate whether prolactin (PRL) modulates 5 alpha-reductase activity (5 alpha-RA), because 5 alpha-RA is known to be a major factor influencing the manifestation of androgenicity. Compared with normal women, euprolactinemic hirsute and both hyperprolactinemic hirsute and nonhirsute women had elevated levels of unbound testosterone (uT). Serum 3 alpha-androstanediol glucuronide (3 alpha-diol-G) was elevated only in patients who were hirsute, and serum 3 alpha-diol-G/uT ratios were elevated in euprolactinemic hirsute patients and normal in hyperprolactinemic hirsute patients. Genital skin 5 alpha-RA in vitro was elevated only in euprolactinemic hirsute women. The previously recognized positive correlation between 5 alpha-RA and the severity of hirsutism was dissociated with hyperprolactinemia. Human PRL incubated in vitro with normal genital skin also inhibited 5 alpha-RA. These data suggest that PRL modulates 5 alpha-RA and peripheral androgen metabolism and that other factors may also be involved in the evolution of hirsutism in hyperprolactinemia.     

Circulating leptin concentrations in women with hirsutism

Objective: To evaluate serum leptin concentrations in hirsute women.Design: Controlled clinical study.Setting: Tertiary institutional hospital.Patient(s): Thirty-three hirsute women and 11 healthy female controls.Intervention(s): Serum samples were obtained at baseline and on day 1 (gonadal stimulation) and day 21 (gonadal suppression) after the IM injection of a single 3.75-mg dose of triptorelin.Main Outcome Measure(s): Leptin, T, sex hormone-binding globulin (SHBG), insulin, and glucose levels and free androgen index.Result(s): Leptin levels were increased in hirsute women in comparison with control subjects at baseline and on day 1. Leptin levels increased on day 1 compared with baseline and then decreased to baseline by day 21. Leptin levels correlated with body mass index (r = −0.76), SHBG levels (r = −0.52), free androgen index (r = −0.38), insulin levels (r = −0.46), and the glucose/insulin ratio (r = −0.38). When the effect of obesity on these results was removed by analysis of covariance and partial correlation analysis, leptin levels remained elevated only on day 1 and the only correlations that remained significant were those of leptin with insulin (r = −0.24) and the glucose/insulin ratio (r = −0.24).Conclusion(s): The increased leptin levels found in hirsute women are related mainly to obesity and also to insulin resistance. Leptin levels increased during gonadal stimulation and returned to baseline during gonadal suppression, suggesting that leptin also is influenced by the gonadal axis.     

Role of androgens in menstrual disorders of nonhirsute and hirsute women, and the effect of glucocorticoid therapy on androgen levels in hirsute hyperandrogenic women

The plasma concentrations of total testosterone, free testosterone index, androstenedione, 17 beta-estradiol, luteinizing hormone, follicle-stimulating hormone, prolactin, and urinary 17-ketosteroid and 17-ketogenic steroid excretion were measured in 48 nonhirsute and 119 hirsute patients. Hormone data were compared within and between groups according to whether the menstrual cycles were eumenorrheic, amenorrheic, or oligomenorrheic. Eleven hirsute women treated with prednisone were followed for 6 months. It was concluded that: (1) androstenedione, testosterone, free testosterone index, and adrenal androgens alone or in combination play a role in the pathogenesis of the hirsutism observed in eumenorrheic women and in the amenorrhea and oligomenorrhea of both hirsute and nonhirsute women; (2) body weight correlated with adrenal adrogens (17-ketosteroids) in nonhirsute women and with androstenedione in hirsute women; (3) prednisone significantly suppressed androstenedione and 17-ketosteroids (p less than 0.05), with a decline of testosterone to 65% and luteinizing hormone to 51% of pretreatment values, with favorable clinical effects on the hirsutism, menstrual dysfunction, and infertility; (4) concentrations of 17 beta-estradiol were lower in amenorrheic than in eumenorrheic and oligomenorrheic women of both groups.     

Treatment of hirsutism with ethinyl estradiol-desogestrel contraceptive pills has beneficial effects on the lipid profile and improves insulin sensitivity

OBJECTIVE: To evaluate the effects on the lipid pattern and insulin sensitivity of hirsute women of an oral contraceptive pill containing 30 microg of ethinyl estradiol and 150 microg of desogestrel. DESIGN: Prospective clinical study. SETTING: Tertiary care institutional hospital. PATIENT(S): 16 hirsute women. INTERVENTION(S): Women were evaluated at baseline and after receiving six cycles of oral contraceptive therapy. MAIN OUTCOME MEASURE(S): Body mass index (BMI); hirsutism score (nine body areas); serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B, lipoprotein(a), and serum adrenal and ovarian androgens; and fasting glucose and insulin concentrations. RESULT(S): The mean serum total, HDL, and LDL cholesterol levels increased after six cycles of oral contraceptive therapy. Levels of HDL cholesterol were < 50 mg/dL in 7 of the 16 patients at baseline; these levels normalized in 4 patients after treatment. Serum total and LDL cholesterol remained within the normal range in all patients before and after therapy. No significant changes were observed in serum triglyceride, apolipoprotein B and lipoprotein(a) concentrations. Fasting insulin levels and insulin resistance as analyzed by homeostasis model assessment were reduced significantly after therapy. No changes in BMI were observed. Administration of oral contraceptive pills signifiCantly reduced the hirsutism score and hyperandrogenemia. CONCLUSION(S): Oral contraceptive pills containing low-dose ethinyl estradiol and desogestrel are effective in controlling hyperandrogenism and hirsutism and ameliorate the abnormal metabolic profile of women with hirsutism.     

Characterization of hyperandrogenism with insulin-resistant diabetes type A

The characterization of the hyperandrogenism of two sisters with type A insulin-resistant diabetes and hirsutism is presented. Testosterone (T) and androstenedione levels were elevated in peripheral serum. These were not markedly affected by infusion of adrenocorticotropic hormone. In patient 1 glucocorticoid suppression decreased T levels by 50% and androstenedione levels by 30% but had no effect on them in patient 2. Estrogen-progestin suppression markedly reduced testosterone levels in both patients. The blood production of T in patient 1 was 0.8 mg/day and in patient 2 was 4.5 mg/day, both of which are elevated. Selective venous catheterization in patient 2 revealed markedly elevated testosterone levels in the ovarian veins, and polycystic ovaries were found at subsequent laparotomy. These endocrine studies have shown that the source of excessive testosterone in these patients is excessive production by the ovaries, and it can be suppressed by oral contraceptives.     

Insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in women with premenstrual syndrome

Objective: To determine whether women with premenstrual syndrome (PMS) have aberrations of the GH axis as has been demonstrated in individuals with depression.

Design: Prospective trial.

Setting: Department of Obstetrics and Gynecology, University of California, Los Angeles.

Patient(s): After prospective screening, 32 healthy women with PMS and 32 asymptomatic controls completed the study.

Intervention(s): Subjects completed a daily PMS symptom diary and a Beck Depression Inventory. They underwent phlebotomy 5 days and 12 days after the LH midcycle surge, which was identified with the use of a urinary LH detection kit.

Main Outcome Measure(s): Serum levels of insulin-like growth factor-1 (IGF-1), insulin-like growth factor-binding protein-3 (IGFBP-3), E₂, and progesterone.

Result(s): Levels of IGF-1, IGFBP-3, E₂, and progesterone did not differ between women with prospectively documented PMS and control subjects.

Conclusion(s): Premenstrual syndrome and affective disorder share common symptoms and possibly a common cause. Biochemical markers such as alterations in the somatotropic system often are associated with major depression. Levels of IGF-1 and IGFBP-3 did not differ between women with PMS and control subjects, supporting the concept that PMS and endogenous depression are biologically distinct entities.