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Purpose Exogenous gonadotrophins administration during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles could significantly alter the endogenous follicular regulation system and could influence oocyte quality. The analysis of the follicular fluid (FF) cytokine and hormone profiles in physiological natural cycles is crucial to appreciate the role of FF milieu on follicle development. So far, the FF cytokine profile has been analyzed only in controlled ovarian stimulation cycles and in modified natural cycles. Our study defines, in physiological natural cycles, the cytokine and hormone profiles of individual FF aspirated from antral follicles. Methods A total of 203 FFs obtained from 83 women with regular menstrual cycles undergoing ovarian tissue cryopreservation were analyzed: 115 FFs from Group 1 (10 to 29 years of age) and 88 FFs from Group 2 (30 to 40 years of age). In individual FF, 27 cytokines were measured with xMAP technology, and progesterone, estrone, estradiol, testosterone, androstenedione concentrations were determined by liquid chromatography–tandem mass spectrometry. Results FF hormone profiles were not different in follicular and luteal phase, suggesting that FF hormones are regulated independently of the endogenous gonadotrophins—possibly because 74% of the punctured follicles, which were ≤6 mm, did not require cyclic pituitary function. The follicle size was influenced not only by the FF cytokine profile but also by the FF hormone profile, both of which are dependent on age. Main Conclusions In physiological natural cycles, FF hormones seems to be regulated independently of the endogenous gonadotropins. Age influences FF hormone and cytokine profiles and the compelling relationship between FF hormones and FF cytokines could influence the follicle development.

The effects of ketoconazole, a synthetic imidazole derivate, were evaluated in 42 women affected by acne (17 cases) and/or hirsutism (36 cases) treated with 400 mg/day for 3-6 months. Androstenedione, total and free testosterone, 5 alpha dihydrotestosterone and dehydroepiandrosterone levels progressively dropped during treatment while 17 alpha hydroxyprogesterone, estradiol, ACTH, cortisol, LH and FSH levels increased. Dehydroepiandrosterone sulfate decreased only towards the end of treatment, while estrone, sex hormone binding globulin, and PRL remained unchanged. Daily mean +/- SD rate of hair growth, measured by a special image analysis processor, decreased within 3 months of therapy from 0.258 +/- 0.058 to 0.184 +/- 0.039 mm/day (P less than 0.02) and mean +/- SD hair diameter from 0.123 +/- 0.015 to 0.110 +/- 0.013 mm (P less than 0.05) together with decreasing hormone levels. The therapeutic effects of ketoconazole on hirsutism was evident at 6 months in only 14 subjects, while no significant change in hirsutism score was recorded in 22 women who failed to complete the therapy. Acne improved in all cases. Several side effects and complications arose during treatment, such as headache, nausea, loss of scalp hair, hepatitis, and biochemical changes. Even though ketoconazole improves hyperandrogenism, only selected patients are eligible for treatment as scrupulous monitoring is required.

The circadian profile of plasma LH concentrations was investigated in 12 healthy anovulatory adolescent women by drawing blood samples every 20 min for 24 h during the early follicular phase. Plasma 17 beta-estradiol, testosterone, and androstenedione levels were measured in the first sample. Ovarian size was measured by ultrasound. According to their mean plasma LH levels, the adolescents were divided into two groups, those with a high plasma LH level (2 Sd or greater than the mean adult value) and those with a normal plasma LH level. The mean plasma estradiol (P less than 0.001) and testosterone (P less than 0.05) levels were higher in the women with high plasma LH levels compared to those in women with normal plasma LH levels. The LH pulse amplitude was greater (P less than 0.05) and the interpulse interval shorter (P less than 0.025) in the high LH group compared to those in the normal LH group. A 24-h periodicity with the highest plasma LH levels and the greatest pulse amplitude in the afternoon was found in high LH group. In the normal LH group, the highest plasma LH levels and greatest pulse amplitude occurred in the first hours of the morning. An accentuated 24-h LH periodicity is typical of puberty, but disappears in adulthood. We have recorded the persistence of pronounced LH circadian changes in anovulatory adolescent women which might be a marker of a continuing maturational process. Furthermore, LH circadian changes have opposing profiles according to the mean LH values, suggesting the presence of different central nervous system pubertal programs.