Diclofenac pyrrolidine versus Ketoprofen for the relief of pain from episiotomy: a randomized controlled trial.

BACKGROUND: The treatment of pain from episiotomy or from tearing of perineal tissues during childbirth is often unapplied, although discomfort may be severe. We performed a randomized double-blind controlled trial to compare the effectiveness and side-effects of two analgesics in the management of postpartum perineal pain. Patient preference toward the two medications was also analyzed. METHODS: A total of 261 women were randomly assigned to receive either Diclofenac hydroxyethyl pyrrolidine (100 mg) (n = 133) or Ketoprofen (100 mg) (n = 128), both given orally every 12 hr up to 48 hr, as necessary. Inclusion criteria were vaginal birth with episiotomy and/or a second- to third-degree tear. Pain ratings were recorded before the administration of the drugs and at 1, 4, 12, and 24 hr after the first dose, according to a 10-cm visual-analog scale. Side-effects and overall opinion on the two treatments were assessed at 24 hr. RESULTS: Diclofenac hydroxyethyl pyrrolidine and Ketoprofen had similar analgesic properties in the first 24 hr postpartum [mean pain rating 3.1 +/- 1.8 and 3.4 +/- 2.0, mean number of doses in 24 hr 1.4 +/- 1.4 and 1.3 +/- 1.5, and proportion of treatment failures 12.8% (17/133) and 16.4% (21/128), respectively]. Significantly fewer subjects in the Diclofenac hydroxyethyl pyrrolidine group than in the Ketoprofen group experienced side-effects (6.8% versus 15.6%; p = 0.038) with an odd risk = 0.39(95% C.I. 0.16-0.95). There were no significant differences in overall patient satisfaction between the two groups. CONCLUSIONS: No main differences were found concerning the relief of pain between the two treatments. Diclofenac hydroxyethyl pyrrolidine may be the preferred choice because it is associated with less adverse reactions, together with a faster action in the relief of pain.

Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol.

OBJECTIVE: To investigate, in a randomized clinical study, the efficacy of an isopropanolic aqueous extract of Cimicifuga racemosa (CR) on climacteric complaints in comparison with low-dose transdermal estradiol (TTSE2). Hormonal parameters, lipid profile and endometrial thickness were also evaluated. METHODS: Sixty-four postmenopausal women were enrolled and over the course of 3 months filled in a diary recording the number of hot flushes per day. Other climacteric symptoms (vasomotor and urogenital symptoms) as well as anxiety and depression, were evaluated at baseline and after 3 months. Gonadotropins (follicle-stimulating hormone (FSH), luetinizing hormone (LH)), prolactin (PRL), 17 beta-estradiol (17beta-E2) and cortisol, lipid profile (total cholesterol high-density lipoprotein (HDL)/low-density lipoprotein (LDL)-cholesterol, triglycerides, liver function (glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase) and endometrial thickness were measured. Patients were randomly allocated to receive, for 3 months, either 40 mg isopropanolic aqueous CR extract daily or 25 microg TTSE2 every 7 days plus dihydrogesterone 10 mg/day for the last 12 days of the 3-month estradiol treatment. RESULTS: Both CR and low-dose TTSE2 significantly reduced the number of hot flushes per day (p < 0.001) and vasomotor symptoms (p < 0.001), starting at the first month of treatment. Such a positive effect was maintained throughout the 3 months of observation, without any significant difference between the two treatments. An identical effect was evident also for both anxiety (p < 0.001) and depression (p < 0.001) which were significantly reduced following 3 months of both CR and low-dose TTSE2. Total cholesterol was unchanged by CR treatment but significantly (p < 0.033) reduced by 3 months of low-dose TTSE2. A slight but significant increase of HDL-cholesterol (p < 0.04) was found only in women treated with CR, while LDL-cholesterol levels were significantly lowered by 3 months of both CR (p < 0.003) and low dose TTSE2 (p < 0.002). Triglycerides were not affected by both treatments, nor was liver function. FSH, LH and cortisol were not significantly affected after the 3-month treatment, while PRL (p < 0.005) and 17 beta-E2 (p < 0.001) were increased slightly only by low-dose TTSE2. Endometrial thickness was not affected by either CR or low-dose TTSE2. CONCLUSIONS: CR (40 mg/day) may be a valid alternative to low-dose TTSE2 in the management of climacteric complaints in those women who cannot be treated with or just refuse conventional strategies.

Metformin administration modulates and restores luteinizing hormone spontaneous episodic secretion and ovarian function in nonobese patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effects of metformin administration on spontaneous LH episodic release in a group of nonobese polycystic ovary (PCOS) patients. DESIGN: Controlled clinical study. SETTING: PCOS patients in a clinical research environment. PATIENT(S): Twenty nonobese PCOS patients were enrolled after informed consent. INTERVENTION(S): All patients underwent hormonal evaluations and a pulsatility study (sampling every 10 minutes for 4 hours) before and at the sixth month of therapy (metformin, 500 mg, p.o. b.i.d.). Ultrasound examinations and Ferriman-Gallwey scoring were also performed. MAIN OUTCOME MEASURE(S): Measurements of plasma LH, FSH, estradiol (E(2)), androstenedione (A), 17-hydroxy-progesterone (17-OHP), and testosterone (T), glucose, insulin, and C-peptide concentrations. RESULT(S): After 6 months of metformin administration, the plasma LH, 17-OHP, A, and T levels and LH/FSH ratio were significantly reduced. Insulin sensitivity, expressed as the glucose-to-insulin ratio, was significantly improved under glucose load after 6 months of treatment. Spontaneous LH episodic release showed a significant reduction in pulse amplitude with no changes in pulse frequency. Menstrual cyclicity was restored in all amenorrheic and oligomenorrheic women. The ovarian volume and Ferriman-Gallwey scores also were significantly reduced. CONCLUSION(S): Metformin administration improves reproductive axis functioning in hyperandrogenic nonobese PCOS patients. By acting on the ovary and restoring normal ovarian activity, metformin positively modulates the reproductive axis (namely GnRH-LH episodic release).

Pulsatile secretory characteristics of allopregnanolone, a neuroactive steroid, during the menstrual cycle and in amenorrheic subjects.

OBJECTIVE: To investigate whether allopregnanolone, a neuroactive steroid involved in modulating behavioural and neuroendocrine functions, shows episodic secretion in eumenorrheic women, during the follicular and luteal phases of the menstrual cycle, and in women with stress-induced amenorrhea. PATIENTS: Six eumenorrheic women and 14 women with hypothalamic amenorrhea were enrolled for the present study. METHODS: All subjects underwent hormonal evaluation in baseline conditions and a pulsatility study to determine LH, cortisol and allopregnanolone episodic release. Eumenorrheic subjects were investigated twice, in the follicular phase (days 3-7) and in the luteal phase (days 18-22) of the menstrual cycle. LH, FSH, prolactin, estradiol, phosphate, DHEA, allopregnanolone and cortisol levels were evaluated in each case. RESULTS: In healthy women, serum gonadotropin and gonadal steroid levels were significantly lower (P<0.01 and P<0.05 respectively) than those in amenorrheic subjects. Allopregnanolone was higher in amenorrheic subjects and during the luteal phase, compared with the follicular phase, of eumenorrheic subjects (P<0.01). Pulse analysis revealed a significant episodic discharge of allopregnanolone in all subjects (follicular phase 6.5+/-0.3 peaks/6 h and luteal phase 5.5+/-0.4 peaks/6 h, hypothalamic amenorrhea 7.0+/-0.7 peaks/6 h) with higher pulse amplitude in amenorrheic subjects and during the luteal phase compared with the follicular phase of the eumenorrheic subjects (P<0.05). Moreover, the specific concordance index demonstrated that allopregnanolone is coupled with LH only during the luteal phase of the cycle and with cortisol during both phases. Allopregnanolone-cortisol coupling was also observed in amenorrheic subjects. CONCLUSIONS: Allopregnanolone is secreted episodically. Both the ovary and adrenal glands release this steroid hormone and it shows temporal coupling with LH only during the luteal phase, with cortisol during both the studied phases of the menstrual cycle in eumenorrheic women and again with cortisol in hypothalamic amenorrheic patients.