Circadian profiles of progesterone, gonadotropins, cortisol and corticotropin in cycling and postmenopausal women.

Little is known about the regulation of temporal variations of progesterone over the 24-hr span in young cycling women as well as in postmenopausal women. The purpose of the present study was to investigate the relationships between diurnal variations of progesterone and diurnal variations of hormones of the gonadotropic and corticotropic axes, and to provide further information on the source of progesterone secretion under physiological conditions. Twenty-four-hour hormonal profiles were explored under well-controlled laboratory conditions in 10 healthy women (21-36 yr old) with normal ovulatory cycles during early-mid follicular and late luteal phases, and in 8 healthy postmenopausal women (48-74 yr old). In young cycling women, significant positive relationships were found between progesterone and follicle-stimulating hormone (FSH) - but not luteinizing hormone (LH) - profiles during late luteal phase. Conversely, during follicular phase, significant positive relationships were evidenced between progesterone and cortisol profiles, but not between progesterone and FSH or LH. In postmenopausal women, strong positive correlations were found between progesterone and corticotropin (ACTH) or cortisol profiles. The present results indicate that during late luteal phase, temporal progesterone profiles are associated with FSH rather than with LH profiles. They also provide evidence that adrenal cortex is a major - or possibly the only - source of progesterone production during the follicular phase of the normal ovulatory cycle, and probably the only source after menopause.

Sleep and hormonal changes in aging.

Age-related sleep and endocrinometabolic alterations frequently interact with each other. For many hormones, sleep curtailment in young healthy subjects results in alterations strikingly similar to those observed in healthy old subjects not submitted to sleep restriction. Thus, recurrent sleep restriction, which is currently experienced by a substantial and rapidly growing proportion of children and young adults, might contribute to accelerate the senescence of endocrine and metabolic function. The mechanisms of sleep-hormonal interactions, and therefore the endocrinometabolic consequences of age-related sleep alterations, which markedly differ from one hormone to another, are reviewed in this article.

Effects of a 3-week dehydroepiandrosterone administration on sleep, sex steroids and multiple 24-h hormonal profiles in postmenopausal women: a pilot study.

OBJECTIVE: Dehydroepiandrosterone (DHEA) administration is widely evocated as a 'fountain of youth', but previous studies have provided inconsistent results. We aimed to investigate in healthy postmenopausal women the effects of a 3-week oral DHEA administration on individual steroid levels, multiple 24-h hormonal profiles and sleep architecture. DESIGN: Seven healthy nonobese postmenopausal women, off hormone replacement therapy for ≥2 months, were investigated in a randomized, crossover, double-blind, placebo-controlled study. For 3 weeks, subjects took daily at 2300 h a capsule of either 50 mg DHEA or placebo. Sleep was polygraphically recorded during the last two nights, and blood samples were drawn at 15-min intervals during the last 24 h. RESULTS: Under DHEA, testosterone and estradiol levels were increased in all individuals. Individual increments were highly variable, not related to each other, and were not related to placebo values. However, the testosterone to estradiol ratio was markedly increased under DHEA. DHEA administration had little, if any, effect on thyroid function, GH secretion, prolactin, ACTH and cortisol profiles. DHEA effects on sleep appeared to be mediated by its conversion to androgens and oestrogens: sleep quality was enhanced by increments in testosterone and dampened by increments in estradiol levels. CONCLUSION: As DHEA-induced elevations in testosterone and estradiol levels varied widely between individuals and were largely unpredictable, DHEA administration might not be the most appropriate approach to compensate for the reduction observed in androgen and oestrogen production in postmenopausal women. DHEA supplementation may result either in sleep stimulation or in inhibition, depending on the ratio between DHEA-induced increments in testosterone vs estradiol.

Impact of GH replacement therapy on sleep in adult patients with GH deficiency of pituitary origin.

OBJECTIVES: We previously reported that adult patients with GH deficiency (GHD) due to a confirmed or likely pituitary defect, compared with healthy controls individually matched for age, gender, and BMI, have more slow-wave sleep (SWS) and higher delta activity (a marker of SWS intensity). Here, we examined the impact of recombinant human GH (rhGH) therapy, compared with placebo, on objective sleep quality in a subset of patients from the same cohort. DESIGN: Single-blind, randomized, crossover design study. METHODS: Fourteen patients with untreated GHD of confirmed or likely pituitary origin, aged 22-74 years, participated in the study. Patients with associated hormonal deficiencies were on appropriate replacement therapy. Polygraphic sleep recordings, with bedtimes individually tailored to habitual sleep times, were performed after 4 months on rhGH or placebo. RESULTS: Valid data were obtained in 13 patients. At the end of the rhGH treatment period, patients had a shorter sleep period time than at the end of the placebo period (479±11 vs 431±19 min respectively; P=0.005), primarily due to an earlier wake-up time, and a decrease in the intensity of SWS (delta activity) (559±125 vs 794±219 µV(2) respectively; P=0.048). CONCLUSIONS: Four months of rhGH replacement therapy partly reversed sleep disturbances previously observed in untreated patients. The decrease in delta activity associated with rhGH treatment adds further evidence to the hypothesis that the excess of high-intensity SWS observed in untreated pituitary GHD patients is likely to result from overactivity of the hypothalamic GHRH system due to the lack of negative feedback inhibition by GH.

Progesterone prevents sleep disturbances and modulates GH, TSH, and melatonin secretion in postmenopausal women.

CONTEXT: A number of neuroactive progesterone metabolites produce sedative-like effects. However, the effects of progesterone administration on sleep are not well characterized. OBJECTIVE: To investigate the effects of a 3-wk progesterone administration on sleep architecture and multiple hormonal profiles. SUBJECTS: Eight healthy postmenopausal women, 48-74 yr old, without sleep complaints or vasomotor symptoms. None was on hormone replacement therapy. They did not take any medication for ≥ 2 months. DESIGN: Randomized, double-blind, placebo-controlled study. For 3 wk, subjects took daily at 2300 h a capsule of either 300 mg of progesterone or placebo. Sleep was polygraphically recorded during the last two nights, and blood samples were obtained at 15-min intervals for 24 h. RESULTS: During the first night (no blood sampling), sleep was similar in both conditions. Under placebo, blood sampling procedure was associated with marked sleep disturbances, which were considerably reduced under progesterone treatment: mean duration of wake after sleep onset was 53% lower, slow-wave sleep duration almost 50% higher, and total slow-wave activity (reflecting duration and intensity of deep sleep) almost 45% higher under progesterone than under placebo (P ≤ 0.05). Nocturnal GH secretion was increased, and evening and nocturnal TSH levels were decreased under progesterone (P ≤ 0.05). CONCLUSIONS: Progesterone had no effect on undisturbed sleep but restored normal sleep when sleep was disturbed (while currently available hypnotics tend to inhibit deep sleep), acting as a "physiologic" regulator rather than as a hypnotic drug. Use of progesterone might provide novel therapeutic strategies for the treatment of sleep disturbances, in particular in aging where sleep is fragmented and of lower quality.

A potential role of endogenous progesterone in modulation of GH, prolactin and thyrotrophin secretion during normal menstrual cycle.

OBJECTIVE: Previous studies investigating the fluctuations of endocrine secretion across the menstrual cycle yielded inconsistent results. Our objective was to evaluate during the menstrual cycle the potential role of endogenous oestradiol and progesterone in the regulation of hormones primarily controlled by the circadian clock and/or the sleep-wake cycle. SUBJECTS AND DESIGN: Ten normally cycling young lean women were investigated once during follicular and once during luteal phase. Sleep was polygraphically recorded, and blood samples were obtained at 20-min intervals for 24 h. RESULTS: Sleep variables and diurnal melatonin and cortisol profiles (hormones primarily controlled by the circadian clock) were similar in both conditions. The TSH evening rise (a circadian marker) was similar in both conditions, but the sleep-related nocturnal TSH decrease occurred earlier during the luteal phase (P = 0.03) and tended to correlate positively with progesterone levels (r(s) = -0.64, P < 0.06). Daytime GH secretion and afternoon/evening PRL secretion (hormones primarily controlled by the sleep-wake homeostasis) were increased in the luteal phase compared with those of the follicular phase (GH: P = 0.04; PRL: P = 0.01). The increase in 24-h GH secretion was associated with higher progesterone levels (r(s) = 0.78, P = 0.02). In luteal phase, the evening PRL rise was associated with higher progesterone (r(s) = 0.70, P = 0.04) and oestradiol (r(s) = 0.72, P = 0.03) levels. CONCLUSION: The present data indicate that in normally cycling young women, daytime GH and PRL secretions are increased in luteal phase. These data also suggest that endogenous progesterone could play a modulation role on pituitary hormone secretion, stimulating GH and PRL release and enhancing the inhibitory action of sleep on TSH secretion.

Sex hormone binding globulin decrease as a potential pathogenetic factor for hirsutism in adolescent girls.

We investigated 252 non-obese female subjects aged 13-39 years to evaluate if an exaggerated descent of sex hormone binding globulin (SHBG) levels during adolescence can play a role in the development of hirsutism. Body hair was assessed according to Ferriman and Gallwey (FG), with a stringent criterion of normality of < or = 4. In 13-14 years girls, SHBG and free testosterone (FT) levels were similar in "hirsute" girls (FG > 4) and controls (FG < or = 4, regular menstrual cycles, no acne). In 15-18 years girls, SHBG values were lower in "hirsute" girls, FT levels were similar in both groups, FG correlated inversely with SHBG. In 19-39 yr women, FT levels were higher in "hirsute" subjects, SHBG values were similar in both groups, FG correlated positively with FT. Lowest SHBG values were observed at 15-18 years, but the slope of the decrease from 13-14 years values was greater in the "hirsute" group. FT values increased progressively with age, but the increase was greater in the "hirsute" group. Those results suggest an important role of SHBG decrease in adolescence vs. a more accentuated testosterone increase in adults, as factors conditioning the development of hirsutism in these two different periods of life.

Sex hormone binding globulin decrease as potential pathogenetic factor for hirsutism in adolescent girls / Disminución de la globulina transportadora de hormonas sexuales como factor patogénico de hirsutismo en la adolescencia

We investigated 252 non-obese female subjects aged 13-39 years to evaluate if an exaggerated descent of sex hormone binding globulin (SHBG) levels during adolescence can play a role in the development of hirsutism. Body hair was assessed according to Ferriman and Gallwey (FG), with a stringent criterion of normality of < 4. In 13-14 years girls, SHBG and free testosterone (FT) levels were similar in "hirsute" girls (FG > 4) and controls (FG < 4, regular menstrual cycles, no acne). In 15-18 years girls, SHBG values were lower in "hirsute" girls, FT levels were similar in both groups, FG correlated inversely with SHBG. In 19-39 yr women, FT levels were higher in "hirsute" subjects, SHBG values were similar in both groups, FG correlated positively with FT. Lowest SHBG values were observed at 15-18 years, but the slope of the decrease from 1314 years values was greater in the "hirsute" group. FT values increased progressively with age, but the increase was greater in the "hirsute" group. Those results suggest an important role of SHBG decrease in adolescence vs. a more accentuated testosterone increase in adults, as factors conditioning the development of hirsutism in these two different periods of life.

Se investigaron 252 mujeres con peso normal, de 13 a 39 años de edad, para evaluar si un descenso exagerado en los niveles de la globulina transportadora de hormonas sexuales ("sex hormone binding globulin"; SHBG) puede tener un rol en el desarrollo de hirsutismo. Este signo fue evaluado con la escala de Ferriman y Gallwey (FG), empleando un criterio riguroso de normalidad < 4. En niñas de 13-14 años, tanto SHBG como la testosterona libre ("free testosterone"; FT) fueron similares en niñas "hirsutas" (FG > 4) y controles (FG < 4, ciclos menstruales regulares, sin acné). En adolescentes de 15-18 años, los valores de SHBG fueron menores en las "hirsutas", los niveles de FT fueron similares en ambos grupos y el índice de FG correlacionó inversamente con SHBG. En las mujeres de 19-39 años, los niveles de FT fueron mayores en las "hirsutas", los valores de SHBG fueron similares en ambos grupos y FG correlacionó positivamente con FT. Los valores más bajos de SHBG se observaron entre 15 y 18 años, pero la pendiente de disminución a partir de los valores de 13-14 años fue mayor en el grupo de "hirsutas". Los valores de FT se incrementaron progresivamente con la edad, pero el aumento fue mayor en el grupo de "hirsutas". Estos resultados sugieren un rol importante del descenso de SHBG en la adolescencia vs. un incremento más acentuado de los niveles de testosterona en las adultas, como factores que condicionan el desarrollo del hirsutismo en esos dos diferentes periodos de la vida.