The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Bone density in a population of long term oral contraceptive pill users does not differ from that in menstruating women.

Prevention of osteoporosis is a major public health issue. Amenorrhoeic women have lower bone density than normally menstruating women, which is related to the duration of amenorrhoea and the severity of oestrogen deficiency. Bone mineral density (BMD) in amenorrhoeic women can be improved by oestrogen replacement in the form of the combined oral contraceptive pill (COCP), so increased BMD might be an important non-contraceptive benefit of the COCP in menstruating women. Previous studies have been variably reported, but have used different methodologies for measurement of BMD. We measured BMD using the DEXA technique in long term COCP users and compared this with menstruating women who had never used the COCP. No differences in bone density were found, suggesting that the COCP does not improve bone mass in menstruating women who are adequately oestrogenised by their own ovaries.

In vitro culture of endometrial stromal and gland cells as a model for endometriosis: the effect of peritoneal fluid on proliferation.

OBJECTIVE: To test the hypothesis that the cell-free fraction of PF from women with endometriosis affects the proliferation of endometrial epithelial and stromal cells in vitro. DESIGN: A cell biologic and immunohistochemical study. SETTING: University teaching hospital. PATIENT(S): Premenopausal women undergoing laparoscopy and women with histologically normal endometrium undergoing hysterectomy were selected. INTERVENTION(S): Peritoneal fluid (PF) and serum were collected at laparoscopy. Endometrial epithelial and stromal cells were obtained by enzymic dissociation of tissue, and epithelium was separated from stromal cells by sieving. Epithelial and stromal cell populations were purified by removal of contaminating cells using Thy-1-and CD-45-labeled immunomagnetic beads. Isolated endometrial gland and stromal cells were cultured in the presence of PF or serum from women with and without endometriosis. MAIN OUTCOME MEASURE(S): Cell proliferation was assessed by measurement of incorporation of 3[H]thymidine after 48 hours in culture. RESULT(S): Isolated endometrial gland and stromal cells were able to proliferate in vitro. The proliferative effect of PF or sera from women with endometriosis did not differ significantly from normal controls. CONCLUSION(S): We conclude that PF from women with endometriosis does not have an additional mitogenic effect compared with women without endometriosis. It may be postulated that the endometrium from women with endometriosis responds differently to the effects of PF.

A randomized, double-blind, placebo-controlled study of luteal phase dydrogesterone (Duphaston) in women with minimal to mild endometriosis.

OBJECTIVE: To compare dydrogesterone with placebos in the treatment of minimal to mild endometriosis. DESIGN: Prospective, double-blind, randomized study. SETTING: Three Obstetrics and Gynaecology Departments in the United Kingdom. PATIENTS: Sixty-two premenopausal women with complaints of pain (n = 12) and infertility with or without pain (n = 50) with minimal to mild endometriosis diagnosed at laparoscopy. Thirty-nine women had a laparoscopy after treatment and 56 women were followed up 12 months after treatment. INTERVENTIONS: Two high doses of dydrogesterone (either 40 or 60 mg) or a placebo, which was given for 12 days, beginning 2 days after the LH surge for a treatment period of 6 months. MAIN OUTCOME MEASURES: Change between before and after treatment endometriosis scores, pregnancy rates (PRs), and pain. RESULTS: Treatment with dydrogesterone did not alter the natural history of endometriosis or PRs when compared with placebo. Pain was reduced significantly during treatment with 60 mg dydrogesterone and this improvement still was evident at 12-month follow-up. CONCLUSION: Luteal phase dydrogesterone reduces pain associated with endometriosis.

The effect of nafarelin on human plasma adrenocorticotrophic hormone and cortisol concentrations.

This study assessed the effects on plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations of 3 months' treatment with intranasal nafarelin 200 micrograms b.d. in 11 women (aged 26-43 years) for the treatment of endometriosis (n = 9), fibroids (n = 1) and pre-menstrual syndrome (n = 1). Serial blood samples were taken over 5 h, before and after nafarelin administration on the first day of treatment, and after 1 and 3 months' treatment. Control samples were taken before and after intranasal placebo administration on the day before nafarelin was commenced. The area under the curve (AUC) for mean ACTH concentrations at each time point from 0 to 240 min was calculated. There were no statistically significant changes in total secretion of either ACTH or cortisol. There was a transient rise in ACTH 30-60 min after nafarelin administration on the first day of treatment in seven out of 11 women. The rise did not exceed the normal range. Seven women with ovarian suppression (oestradiol concentration < 175 pmol/l by day 28) had consistently lower mean ACTH concentrations at all time points than the four remaining women who had oestradiol concentrations 222-880 pmol/l by day 28. Cortisol concentrations were unaffected by nafarelin. We conclude from the results of this study that 3 months' treatment with nafarelin has no effects on adrenal function, as assessed by ACTH and cortisol concentrations.