Pituitary-adrenal function in ten patients receiving medroxyprogesterone acetate for true precocious puberty.
01 May 1970-The Journal of Clinical Endocrinology and Metabolism (The Endocrine Society)-Vol. 30, Iss: 5, pp 653-658
TL;DR: The data suggest that MPA in the dosages tested has a suppressive effect on pituitary ACTH synthesis and/or release, however, no clinical evidence of hypoadrenocorticism was observed in these patients even during periods of stress.
Abstract: The effect of medroxyprogesterone acetate (MPA) on pituitary-adrenal function was investigated in 10 patients with true precocious puberty. Although the patients receiving MPA responded to exogenously administered ACTH by a rise in the plasma 17-hydroxycorticosteroids, the mean values of both the pre- and post-ACTH levels were statistically lower than those obtained in the controls. In 7 of the 8 patients the increase of the urinary 17-ketogenic steroids following the oral administration of metyrapone was less than 2-fold. The data suggest that MPA in the dosages tested has a suppressive effect on pituitary ACTH synthesis and/or release. Despite this inhibition, however, no clinical evidence of hypoadrenocorticism was observed in these patients even during periods of stress. When the drug was discontinued, pituitary-adrenal function rapidly returned toward normal, suggesting that the suppressive effect of MPA was a relatively mild one.
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TL;DR: In the patients with central precocious puberty or combined peripheral and central Precocious puberty, LHRHa therapy caused suppression of gonadotropin and sex steroid levels, stabilization or regression of secondary sexual characteristics, and decreases in growth rate and in the rate of bone age maturation, but is ineffective in the therapy of peripheral precociousuberty.
178 citations
TL;DR: The gonadotropin-releasing hormone–like agonist d-Trp6-Pro9-NEt-LHRH (LHRHa) has been shown to induce a reversible short-term suppression of gonadotropic substances and gonadal steroids in patients with central precocious puberty, and complete suppression of the pituitary-gonadal axis can be maintained by LHRHa.
Abstract: The gonadotropin-releasing hormone-like agonist D-Trp6-Pro9-NEt-LHRH (LHRHa) has been shown to induce a reversible short-term suppression of gonadotropins and gonadal steroids in patients with central precocious puberty. Since accelerated statural growth and bone maturation are clinical features of precocity not well controlled by conventional therapies, we examined the effects of prolonged LHRHa therapy for 18 consecutive months on growth and skeletal maturation in nine girls with neurogenic or idiopathic precocious puberty. Suppression of gonadotropin pulsations and gonadal steroids was maintained in all subjects. Growth velocity fell from a mean rate (+/- S.E.M.) of 9.35 +/- 0.64 cm per year during the 19 months before treatment to 4.58 +/- 0.60 cm per year during treatment (P less than 0.001). Bone age advanced a mean of 9.4 +/- 2.3 months during treatment. These changes resulted in a mean increase of 3.3 cm in predicted height (P less than 0.01). Complete suppression of the pituitary-gonadal axis can be maintained by LHRHa therapy, resulting in slowing of excessively rapid growth and skeletal maturation and in increased predicted adult height in girls with precocious puberty.
149 citations
TL;DR: Detailed characterization of children with precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable gonadotropin secretion, and GnRHa therapy of CPP provides a unique opportunity to study the effects of gonadal sex steroids on GH secretion and somatomedin-C (Sm-C) generation during sexual maturation.
Abstract: Studies utilizing the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists (GnRHa), like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion. This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty (CPP), a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects. In our series, 74 children with CPP have been treated during the last 5 yr with the potent GnRH agonist, [D-Trp6, Pro9-ethylamide(NEt)]GnRH. Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary gonadotropin secretion, GnRHa therapy resulted in a fall of gonadal sex steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages. Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa therapy on final height must await further longitudinal study. The selective nature of GnRHa suppression of gonadarche also permits an investigation of the natural history of adrenarche and its discrete influences upon skeletal growth and maturation. In addition, GnRHa therapy of CPP provides a unique opportunity to study the effects of gonadal sex steroids on GH secretion and somatomedin-C (Sm-C) generation during sexual maturation. Finally, the detailed characterization of children with precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable gonadotropin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
144 citations
TL;DR: A thorough review of the literature from studies with medroxyprogesterone acetate is presented, finding that injectable contraceptives do seem to cause a greater amount of menstrual disorders including amenorrhea than other types of contraception, they can however be used during lactation without effect of the lactating factor.
Abstract: The most widely used longterm injectable female contraceptive is depot medroxyprogesterone acetate. Its advantages as a contraceptive its history of use its present legal status in Australia and its mode of action are discussed. The major concern is that involving interpretation of animal toxicology data related to various carcinogenic side effects of the drug. Of the great amount of human data so far gathered none has shown any evidence of human risk with medroxyprogesterone acetate. There is continuing controversy regarding the size duration and type of studies which must be undertaken in order to exclude all hint of risk. A thorough review of the literature from studies with medroxyprogesterone acetate is presented. Injectable contraceptives do seem to cause a greater amount of menstrual disorders including amenorrhea than other types of contraception. They can however be used during lactation without effect of the lactating factor. Studies must be undertaken to assess whether they do carry risks to the baby through the milk. Few metabolic changes have been confirmed. The relationship which has been shown to exist either negative or positive between medroxyprogesterone acetate and cervical breast endometrial or liver cancer is discussed in detail.
140 citations
TL;DR: MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary, and a blunted response to maximal ACTH stimulation was found.
Abstract: Twelve cancer patients and one patient with diabetes mellitus were treated with medroxyprogesterone acetate (MPA) by intramuscular injection in a total weekly dose of 400, 700, or 1200 mg. The treatment reduced the plasma cortisol concentration by 76% in the AM hours (21 → 5.0 μg/dl) and by 75% in the PM hours (12.8 → 3.2 μg/dl). Cortisol production rate decreased by 67% (19 → 6.2 mg/24 hrs). The 24 hour profile of plasma cortisol concentration measured in 3 patients showed zero secretion over this period. Low plasma ACTH values prevailed during treatment, and a blunted response to maximal ACTH stimulation was found. No evidence of adrenal insufficiency was observed in any patient, even though in some patients the plasma cortisol concentration remained at zero for many weeks. MPA has cortisol-like effects and the suppression of adrenal function is probably mediated by a negative feedback action on the hypothalamus or pituitary.
101 citations