J. Huber

The influence of hormone replacement therapy on skin ageing: a pilot study.

OBJECTIVESnWe studied the effect of hormonal treatment on skin ageing in menopausal women.nnnMETHODSnTwenty-four patients (45-68 years; mean age, 54.9 years) without hormone treatment for at least 6 months were included. Patients were assigned to three therapy groups: 1, oestrogen only (Estraderm TTS 50) (n=6); 2, transdermal oestrogen and progesterone (Estraderm TTS 50 and 0.4 mg progesterone vaginal suppository) (n=7); and 3, oral oestrogen and progesterone (2 mg Progynova and 0.4 mg progesterone vaginal suppository) (n=8). One group without therapy was included as a control group (n=3). Treatment was continued for 6 months. Three patients, one from group 2 and two from group 3, discontinued therapy before the study endpoint. The following skin parameters were measured at monthly intervals during treatment: skin surface lipids, epidermal skin hydration, skin elasticity and skin thickness. Concomitant clinical evaluation included a subjective clinical evaluation form, a patient questionnaire and laboratory tests for oestradiol, progesterone and follicle stimulating hormone.nnnRESULTSnMean levels of epidermal skin moisture, elasticity and skin thickness were improved at the end of treatment based on both subjective and objective evaluation in patients with hormone replacement therapy (HRT). Skin surface lipids were increased during combined HRT, which may reflect stimulatory effects of the progestagen component on sebaceous gland activity, while oestrogen alone has a sebum-suppressive action. In the HRT groups, the questionnaire for climacteric complaints demonstrated significant improvements, while laboratory tests showed increases in oestradiol and progesterone and decreases in FSH.nnnCONCLUSIONSnHRT with the mentioned regimes significantly improved parameters of skin ageing.

Pharmacokinetics of Implanon. An integrated analysis.

The aims of this paper were to present data on the pharmacokinetics, clearance, bioavailability, and in vivo absorption of etonogestrel (ENG); to present the results of a longitudinal analysis of the plasma concentration-time curves of ENG; and to present the results of a cross-sectional analysis on the association of body weight with serum ENG concentrations. Implanon had an absorption rate of almost 60 micrograms/day after 3 months, which slowly decreased to 30 micrograms/day at the end of 2 years. The bioavailability over this period of time was constant and close to 100%. The clearance remained around 7.5 L/h. With a bioavailability and clearance that remained constant, it was concluded that accumulation of ENG does not occur. After Implanon insertion, serum concentrations increased within 8 h to concentrations associated with ovulation inhibition. Maximum mean serum concentrations (Cmax) amounted to 813 pg/mL and the time (tmax) to reach Cmax was 4 days. After reaching Cmax, ENG serum concentrations declined to about 196 pg/mL at the end of the first year, followed by a slow decline to 156 pg/mL at the end of the third year. After removal of Implanon, serum ENG concentrations declined to levels less than the detection limit of the assay (20 pg/mL) within 1 week. Lower body weight was associated with higher serum ENG concentrations.

Pharmacokinetics of etonogestrel released from the contraceptive implant Implanon

Eight healthy women between 22 and 40 years of age participated in this prospective open study of 2 years duration. Either on or between days 1 to 7 of a spontaneous menses, an intravenous bolus dose of 150 micrograms etonogestrel (3-ketodesogestrel) was given. During days 1-5 of a subsequent spontaneous cycle, the single-rod contraceptive implant (Implanon) was inserted in the upper arm of the volunteer. One year after placement of the implant, another intravenous bolus dose was given (implant in place), and a third bolus dose was given after 2 years, with the implant removed. Frequent serum sampling immediately after the intravenous dosings of etonogestrel was done to study the primary pharmacokinetic parameters, i.e., volume of distribution and clearance, allowing the calculation of the absorption rate and bioavailability of the implant, as a function of time. Results showed that etonogestrel released from Implanon has an absorption rate of approximately 60 micrograms/day after 3 months, which slowly decreases to 30 micrograms/day at the end of 2 years. The bioavailability over this period of time was constant and close to 100%. The clearance remained around 7.5 L/h. With a bioavailability and clearance that remained constant, it may be concluded that there is no accumulation of etonogestrel.

Ovarian function during and after treatment with the new progestagen Org 30659.

OBJECTIVEnTo evaluate ovarian function during 21 days of oral administration of different doses of Org 30659, a novel selective progestagenic steroid.nnnDESIGNnRandomized, double-blind, dose-finding study.nnnSETTINGSnThree centers in Austria, Sweden, and the United Kingdom.nnnPARTICIPANTSnEighty-one healthy women 19-40 years of age with regular ovulatory cycles.nnnINTERVENTIONnDaily oral administration of 0.060, 0.120, 0.180, or 0.240 mg of Org 30659, or 0.075 mg desogestrel (reference group), for 21 days.nnnMAIN OUTCOME MEASURE(S)nOnce-daily measurements of follicular diameter and 17-beta estradiol, progesterone, FSH, and LH levels.nnnRESULT(S)nDaily treatment with Org 30659 for 21 days caused dose-dependent suppression of ovarian activity. No ovulation was observed in any study group. On average, ovulation returned 16.5 to 22.1 days after treatment. The effects of desogestrel, 0.075 mg, were similar to those of 0.060 and 0.120 mg of Org 30659. All doses were well tolerated, as shown by the type of side effects that occurred, the absence of an effect on physical and laboratory findings, and the low rate of study discontinuation.nnnCONCLUSION(S)nDaily oral administration of 0.060-0.240 mg of Org 30659 suppresses ovarian function to a level sufficient to inhibit ovulation. This effect is dose-dependent, and the suppressive effect is readily reversible at all doses tested. Org 30659 can thus be safely administered orally for 21 days to healthy female volunteers in a dosage of 0.060 mg/d to 0.240 mg/d.

Effect of hormone replacement therapy on growth hormone stimulation in women with premature ovarian failure

OBJECTIVEnTo assess the effect of oral hormone replacement therapy (HRT) on body weight, insulin-like growth factor I (IGF-I), and GH response to exogenous GHRH [corrected] in women with premature ovarian failure (POF) [corrected].nnnDESIGNnControlled clinical study.nnnSETTINGnOutpatients studied in the department of endocrinology of the University Hospital in Vienna.nnnPATIENT(S)nTwenty-four women with POF (study group) and 24 volunteers with normal ovarian cycles (control group).nnnINTERVENTION(S)nPituitary GHRH [corrected] stimulation was performed in all women at study entry and in patients with POF after 1, 6, and 12 months of standard oral HRT. Blood samples were collected from 15 minutes before to 120 minutes after GHRH administration [corrected]. Body weight also was evaluated.nnnRESULT(S)nNo differences in baseline and stimulated serum GH were found either between POF women and controls or in POF women during HRT. Women with POF without HRT had significantly higher IGF-I levels; a reduction in circulating IGF-I levels occurred during HRT. Body weight remained stable.nnnCONCLUSION(S)nOur results show the following: [1] Women with POF have similar Gh secretion patterns as healthy age-matched women; [2] physiologic HRT has no impact on GHRH-induced [corrected] GH stimulation; and [3] HRT has no impact on body weight in women with POF.