Sirpa Ranta

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Late follicular phase administration of mifepristone suppresses circulating leptin and FSH – mechanism(s) of action in emergency contraception?

European Journal of Endocrinology (2005)

Riikka Leminen Taneli Raivio Sirpa Ranta Joachim Oehler Helena von Hertzen

Objective : Low dose mifepristone (RU486) is highly effective in emergency post-coital contraception (EC), although the mechanism(s) of action remains unclear. We studied the endocrine actions of 10 mg mifepristone administered orally as a single dose to eight healthy volunteers (aged 20–45 years) during the late follicular phase. Methods : Serum levels of LH, FSH, oestradiol, progesterone, leptin, mifepristone, cortisol, and gluco-corticoid bioactivity (GBA) were measured before and 1, 2, 4 and 8 h after ingestion of mifepristone on cycle day 10 or 11 (study day 1), and follow-up was continued for 10 days. Ovarian ultrasonography was performed on study days 1 and 7. Similar measurements were carried out during a control cycle. Results : Mifepristone postponed ovulation, as evidenced by a 3.4±1.1 day (means± s.d. ) delay ( P < 0.005) in the LH surge and 3.6±4.0 day prolongation of the treatment cycle ( P = 0.08). During the mifepristone cycle, an LH surge was displayed by five subjects when serum mifepristone levels had declined to 9.5±7.1 nmol/l. During the day of mifepristone administration, circulating GBA ( P < 0.001) and leptin ( P < 0.001) levels declined. On the day after mifepristone administration, mean serum FSH and leptin levels were lower than pretreatment values (3.8±1.8 IU/l vs 5.2±1.1 IU/l, n = 7, P < 0.05; 28.9±6.7 μg/l vs 33.2±9.0 μg/l, n = 7, P < 0.05 respectively), and the corresponding difference in the mean serum oestradiol concentration was borderline (452±252 pmol/l vs 647±406 pmol/l, n = 7, P = 0.056). In contrast to the control cycle, individual leptin levels declined during the follow-up after ingestion of mifepristone ( n = 8, P < 0.01). Conclusions : These data showed that the commonly employed dose of mifepristone for EC delays ovulation and prolongs the menstrual cycle, when given during the late follicular phase. The mechanism of action of mifepristone may include a reduction of FSH secretion via a decrease in circulating leptin.

Abortifacient

10.1530/eje.1.01884

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Citations (8)

Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants

Contraception (1997)

Irving Sivin Pekka Lähteenmäki Sirpa Ranta Philip D. Darney Cindy Klaisle

In a three-year randomized trial that included 398 women, blood samples were collected for the purpose of assaying levonorgestrel concentrations in women using a new two-rod contraceptive implant system or an earlier implant formulation, Norplant®-2 implants. Sample collection was at 1, 3, 6, 9, and 12 months after placement and semiannually thereafter through three years. Resulting assays and analyses showed that levonorgestrel concentrations of each implant formulation decreased significantly with time after placement, with increasing body weight, and with ponderal index. In the third year, several measures indicated that concentrations of the contraceptive drug were higher in women using the LNG ROD implants than in users of the original formulation. No pregnancies occurred among women in either group in the three years. This study provides evidence that the minimum levonorgestrel concentration needed to protect against pregnancy is below 200 pg/ml, and possibly is below 175 pg/ml.

Levonorgestrel

Contraceptive implant

10.1016/s0010-7824(96)00276-4

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Citations (65)

Effect of antiprogesterone mifepristone followed by misoprostol on circulating leptin in early pregnancy

Acta Obstetricia Et Gynecologica Scandinavica (2005)

Helena Honkanen Sirpa Ranta Olavi Ylikorkala Oskari Heikinheimo

Background. To study the role of progesterone (P4) in the regulation of circulating leptin in early human pregnancy, we measured the levels of leptin before and after administration of the antiprogestin mifepristone, followed by misoprostol in early pregnancy. Methods. Thirty-four women requesting termination of pregnancy, with ≤63 days of amenorrhea, received 200 mg of mifepristone on day 0, followed by either oral or vaginal administration of 0.8 mg of misoprostol on day 2. Five serial serum samples were assayed for leptin, human chorionic gonadotrophin (hCG), P4, estradiol (E2), cortisol, and mifepristone. Results. Circulating leptin concentrations decreased by 8.7 ± 29.7% (mean ± standard deviation) (p < 0.05) following the ingestion of mifepristone. After misoprostol administration on day 2, a decrease of 12.6 ± 17.0% (p < 0.05) was followed by a rebound on day 3 to 87.6 ± 25.7% of the pretreatment values. Two weeks after mifepristone, leptin levels had declined by 25.4 ± 30.4%. In contrast, E2, P4, and hCG concentrations continued to increase following mifepristone, followed by rapid declines from day 2 to day 3. Serum cortisol concentrations increased by 89.7% ± 82.7% in response to mifepristone, but this increase did not correlate with the decrease in leptin. The decrease in leptin levels on day 2 correlated with the decreases in P4 (r = 0.37, p < 0.05) and in E2 (r = 0.44, p < 0.05) levels. Conclusions. The fall in leptin levels following mifepristone implies a role for P4 in the regulation of leptin in early pregnancy. Moreover, the significant correlation between the changes in leptin and those of P4 and E2 at the time of luteolysis suggests that corpus luteum may also play a role in the regulation of circulating leptin in early pregnancy.

10.1080/j.0001-6349.2005.00626.x

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Citations (0)

Effects of rifampicin on porphyrin metabolism in healthy volunteers

Basic & Clinical Pharmacology & Toxicology (2022)

Hanna Tolonen Sirpa Ranta Esa Hämäläinen Raili Kauppinen Janne Hukkanen

Abstract Pregnane X receptor (PXR) is known to stimulate haem synthesis, but detailed knowledge on the effects of PXR activation on porphyrin metabolism in humans is lacking. We utilized a randomized, crossover, open (blinded laboratory) and placebo‐controlled trial with 600‐mg rifampicin or placebo dosed for a week to investigate the effects of PXR activation on erythrocyte, plasma, faecal and urine porphyrins. Sixteen healthy volunteers participated on the trial, but the number of volunteers for blood and urine porphyrin analyses was 15 while the number of samples for faecal analyses was 14. Rifampicin increased urine pentaporphyrin concentration 3.7‐fold (mean 1.80 ± 0.6 vs. 6.73 ± 4.4 nmol/L, p = 0.003) in comparison with placebo. Urine coproporphyrin I increased 23% ( p = 0.036). Faecal protoporphyrin IX decreased (mean 31.6 ± 23.5 vs. 19.2 ± 27.8 nmol/g, p = 0.023). The number of blood erythrocytes was slightly elevated, and plasma bilirubin, catabolic metabolite of haem, was decreased. In conclusion, rifampicin dosing elevated the excretion of certain urinary porphyrin metabolites and decreased faecal protoporphyrin IX excretion. As urine pentaporphyrin and coproporphyrin I are not precursors in haem biosynthesis, increased excretion may serve as a hepatoprotective shunt when haem synthesis or porphyrin levels are increased.

10.1111/bcpt.13826

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Citations (2)

Pharmacokinetics and endometrial tissue levels of levonorgestrel after administration of a single 1.5-mg dose by the oral and vaginal route

Fertility and Sterility (2005)

Luigi Devoto Ariel Fuentes Alberto Palomino Alejandra Araya Espinoza Paulina Kohen

Levonorgestrel

Ethinylestradiol

10.1016/j.fertnstert.2005.01.106

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Citations (28)

Two-year performance of a Nestorone®-releasing contraceptive implant: a three-center study of 300 women