Efficacy on hyperandrogenism and safety of a new oral contraceptive biphasic formulation containing desogestrel.

A new biphasic oral contraceptive (OC) containing ethinylestradiol and desogestrel (DGS) in both phases of the cycle (7 days 40/25 micrograms + 15 days 30/125 micrograms) was tested for its reliability, tolerability, safety and effectiveness on endocrine correlates of hyperandrogenism and acne in normal women (n = 30) and women suffering from acne (n = 33). Contraceptive efficacy was absolute and, despite 3 drop-outs in the group with acne (4.7% of total patients), subjective complaints were limited to a small number of women. Cycle control was satisfactory in both groups. Fibrinopeptide A remained stable under the treatment, whereas HDL-chol increased and the ratio between LDL-chol and HDL-chol decreased during pill intake. Other advantageous effects were obtained on the circulating androgen profile with increased sex hormone binding globulin concentrations coupled with significantly reduced total and free testosterone levels. In 23 out of 30 patients with acne (76.6%) the skin disease disappeared after 9 months of therapy and in 3 severely affected subjects the pathology changed into a pattern of mild or moderate degree. Our results indicate that the tested new biphasic OC combination is reliable, well tolerated, safe and effective against hyperandrogenism.

Contraception in older woman.

Oral contraception (OC) in the premenopause has been recently proposed as treatment for control and prevention of the putative symptoms typical of this period of life. Indeed, menstrual cycle disturbances and climacteric symptoms frequently occur at this age. The major aim of normal contraception is resultant maintenance of normal sexual activity. The effects of one OC containing 20 mcg ethinylestradiol and 150 mcg desogestrel (EE/DOG) were studied. Treatment did not significantly modify both lipid metabolism (triglycerides, total cholesterol, HDL, LDL, Apo A, Apo B) and clotting system (fibrinogen, PT, PTT, antithrombin III, fibrinopeptide A). No significant modifications of oral glucose tolerance test (OGGT) occurred after EE/DOG treatment. Also, bone density was not modified during estro-progestinic administration. From our experience, if there are no risk factors such as smoking, obesity or hypertension, the OCs could be used until menopause for absolute contraceptive efficacy, good tolerance and lack of side effects.

PIP: At Cagliari Hospital in Italy, the department of obstetrics and gynecology studied the efficacy and safety of a combined oral contraceptive (OC) containing 20 mcg of ethinyl estradiol and 150 mcg of desogestrel in 61 nonsmoking women aged 41-48. The women were followed for up to five years. After the second cycle of treatment, the mean length of the menstrual cycle and menses standardized at 26 and 4 days, respectively. By 12 months of OC treatment, the slight side effects either had disappeared or had significantly declined. No woman gained weight. Blood pressure did not change significantly. Lipid metabolism did not change significantly. There were only small insignificant increases in high and low density lipoprotein cholesterol, triglycerides, and apolipoproteins A. After 6, 12, and 24 months of OC treatment, sex hormone binding globulin levels increased significantly (1.83 vs. 3.6 mcg/dl; p 0.05). The OC did not significantly affect blood coagulation markers (fibrinogen, prothrombin time, partial thromboplastin time, antithrombin III, and fibrinopeptide A). It had no effect on fasting blood glucose and insulin levels and their response to the oral glucose tolerance test. The researchers conducted bone density measurements in the lumbar spine (L2-L4) of 37 women aged 45-48. The OC did not alter bone density. These results suggest that this low-estrogen-dose combined OC is a safe and effective contraceptive in perimenopausal women and has good acceptability and good cycle control without considerable side effects. The OC also exhibited the capability of further minimizing the thrombogenic effects of low-dose OCs.

Pregnancy following regression of uterine submucosal leiomyoma with GnRH therapy; a case report.

A patient with a history of two spontaneous abortions, at the 16th and 20th week, respectively, and one intra-uterine fetal death at the 26th week of gestation was investigated. The sole abnormal condition that could be evidenced was a submucosal leiomyoma of 56 mm in diameter in the uterine fundus. Administration of gonadotropin/releasing hormone analog (GnRHa) for 10 months resulted in complete disappearance of myoma. Direct intraperitoneal insemination following induction of ovulation resulted in pregnancy. In a patient harboring uterine leiomyomas, adversely affecting conception and pregnancy outcome, GnRHa treatment may be an initial approach allowing to avoid pelvic surgery. As the beneficial effect of GnRHa might be temporary, assisted reproduction procedures might anticipate conception.

Pregnancy following combined growth hormone--pulsatile GnRH treatment in a patient with hypothalamic amenorrhoea.

A patient with hypothalamic amenorrhoea and a poor response in terms of pituitary growth hormone (GH) to acute administration of growth hormone-releasing factor has been treated with pulsatile gonadotrophin-releasing hormone (GnRH) combined with GH to induce ovulation. GH was administered daily until signs of ovulation were detected. The luteal phase was supported by pulsatile GnRH only. Combined treatment gave an improved follicular recruitment, higher plasma levels of 17 beta-oestradiol and an earlier ovulation, compared to the previous cycle with pulsatile GnRH only. The result was a twin pregnancy which ended with the birth of two healthy male babies. The role of GH in potentiating the ovarian response to gonadotrophins, as well as the GH secretion abnormalities associated with dysfunctions of the hypothalamic - pituitary - gonadal axis, might provide a rationale for combined GH and pulsatile GnRH treatment in such patients.

Progestins modulate the action of estrogen on gonadotropin-releasing hormone, luteinizing hormone and prolactin in the rat.

The aim of the present study was to evaluate the effect of progesterone and of various synthetic progestins on hypothalamic gonadotropin-releasing hormone (GnRH) and on pituitary and plasma LH and prolactin (Prl) concentrations in ovariectomized rats. Groups of 6 rats were treated for 2 weeks with a pharmacological dose of progesterone, desogestrel, medroxyprogesterone acetate or norethisterone enanthate (NET). The same treatment was also repeated in association with estradiol benzoate (EB). Groups of ovariectomized rats were also treated with EB only or vehicle. Ovariectomized rats showed hypothalamic concentrations of GnRH significantly higher than control rats. Progesterone and NET significantly increased GnRH concentrations and reversed the EB-induced changes. Rats treated with progesterone and NET also showed reduced pituitary LH concentration, with high plasma LH levels. All progestins blocked the increase of pituitary LH induced by EB, but were inactive in influencing the inhibitory effect of EB on plasma LH levels. The administration of progesterone and progestins did not induce significant changes of pituitary or plasma Prl, but reversed the EB-induced increase. These results showed that progesterone and progestins have a marked effect on hypothalamic and pituitary hormone secretion and that they modulate estrogen-induced effects.