Stanczyk, F. Z. (1999). Pharmacokinetics of progesterone administered by the oral and parenteral routes. The Journal of Reproductive Medicine, 44(2 Suppl), 141-147.
Stanczyk FZ. Pharmacokinetics of progesterone administered by the oral and parenteral routes. J Reprod Med. 1999;44(2 Suppl):141-147.
Stanczyk, F. Z. "Pharmacokinetics of progesterone administered by the oral and parenteral routes." The Journal of Reproductive Medicine, vol. 44, no. 2 Suppl, 1999, pp. 141-147.
For EndNote, Zotero or Mendeley:
License
No open license is recorded for this paper. Reuse terms are set by the publisher.
Progestogens, which include the natural hormone, progesterone, and synthetic steroid derivatives, are used to treat a variety of reproductive disorders. Since synthetic progestogens are often associated with undesirable side effects, improved formulations and modes of administration of progesterone have been sought. In order to find an optimal therapeutic agent, different progesterone formulations and routes of administration have been studied. This paper explains several methods of measuring progesterone levels and summarizes clinical data on the pharmacokinetic profiles of natural progesterone administered by the oral, intramuscular, vaginal, intranasal, percutaneous, sublingual and rectal routes.
Steiner AZ et al., 2017·JAMA·Free full text on PubMed Central
Despite lack of evidence of their utility, biomarkers of ovarian reserve are being promoted as potential markers of reproductive potential. To determine the associations between biomarkers of ovarian reserve and reproductive potential among women of late reproductive age. DESIGN, SETTING, Prospective time-to-pregnancy cohort study (2008 to date of last follow-up in March 2016) of women (N = 981) aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, recruited from the community in the Raleigh-Durham, North Carolina, area. Exposures: Early-follicular-phase serum level of antimüllerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and urinary level of FSH. The primary outcomes were the cumulative probability of conception by 6 and 12 cycles of attempt and relative fecundability (probability of conception in a given menstrual cycle). Conception was defined as a positive pregnancy test result. A total of 750 women (mean age, 33.3 [SD, 3.2] years; 77% white; 36% overweight or obese) provided a blood and urine sample and were included in the analysis. After adjusting for age, body mass index, race, current smoking status, and recent hormonal contraceptive use, women with low AMH values (<0.7 ng/mL [n = 84]) did not have a significantly different predicted probability of conceiving by 6 cycles of attempt (65%; 95% CI, 50%-75%) compared with women (n = 579) with normal values (62%; 95% CI, 57%-66%) or by 12 cycles of attempt (84% [95% CI, 70%-91%] vs 75% [95% CI, 70%-79%], respectively). Women with high serum FSH values (>10 mIU/mL [n = 83]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (63%; 95% CI, 50%-73%) compared with women (n = 654) with normal values (62%; 95% CI, 57%-66%) or after 12 cycles of attempt (82% [95% CI, 70%-89%] vs 75% [95% CI, 70%-78%], respectively). Women with high urinary FSH values (>11.5 mIU/mg creatinine [n = 69]) did not have a significantly different predicted probability of conceiving after 6 cycles of attempt (61%; 95% CI, 46%-74%) compared with women (n = 660) with normal values (62%; 95% CI, 58%-66%) or after 12 cycles of attempt (70% [95% CI, 54%-80%] vs 76% [95% CI, 72%-80%], respectively). Inhibin B levels (n = 737) were not associated with the probability of conceiving in a given cycle (hazard ratio per 1-pg/mL increase, 0.999; 95% CI, 0.997-1.001). Conclusions and Relevance: Among women aged 30 to 44 years without a history of infertility who had been trying to conceive for 3 months or less, biomarkers indicating diminished ovarian reserve compared with normal ovarian reserve were not associated with reduced fertility. These findings do not support the use of urinary or blood follicle-stimulating hormone tests or antimüllerian hormone levels to assess natural fertility for women with these characteristics.
Although widely used, the mechanisms of action of the levonorgestrel emergency contraceptive pill (LNG ECP) are still unclear. There are increasing data to indicate that LNG is particularly effective as an ECP by interrupting follicular development and ovulation. An important outstanding question is whether it has any effect on fertilization or implantation. Ninety-nine women participated; they were recruited at the time they presented with a request for emergency contraception. All women took LNG 1.5 mg in a single dose during the clinic consultation. A blood sample was taken immediately prior to ingestion of the ECP for estimation of serum LH, estradiol and progesterone levels to calculate the day of ovulation. The specimens were analyzed in a single batch. Based on these endocrine data, we estimated the timing of ovulation to be within a +/-24-h period with an accuracy of around 80%. Women were followed up 4-6 weeks later to ascertain pregnancy status. The effectiveness of ECP when taken before and after ovulation was determined. Three women became pregnant despite taking the ECP (pregnancy rate, 3.0%). All three women who became pregnant had unprotected intercourse between Days -1 and 0 and took the ECP on Day +2, based on endocrine data. Day 0 was taken as ovulation day. Among 17 women who had intercourse in the fertile period of the cycle and took the ECP after ovulation occurred (on Days +1 to +2), we could have expected three or four pregnancies; three were observed. Among 34 women who had intercourse on Days -5 to -2 of the fertile period and took ECP before or on the day of ovulation, four pregnancies could have been expected, but none were observed. We found major discrepancies between women's self-report of stage of the cycle and the dating calculation based on endocrine data. These data are supportive of the concept that the LNG ECP has little or no effect on postovulation events but is highly effective when taken before ovulation.
Cardiovascular disease, the major cause of death in post-menopausal women, can be reduced by replacement of ovarian steroid hormones. To compare medroxyprogesterone with progesterone as the progestin in hormone replacement therapy from the standpoint of coronary artery vasospasm, we treated ovariectomized rhesus monkeys with physiological levels of estradiol-17 beta in combination with medroxyprogesterone or progesterone for four weeks. Coronary vasospasm in response to pathophysiological stimulation without injury showed that progesterone plus estradiol protected but medroxyprogesterone plus estradiol failed to protect, allowing vasospasm. We conclude that medroxyprogesterone in contrast to progesterone increases the risk of coronary vasospasm.
The bioavailability of micronized progesterone (P) was studied by measuring sequential serum P concentrations after a single bolus of 50-200 mg P given sublingually, orally (capsule and tablet), vaginally and rectally (suppositories) during the follicular phase in a group of normally menstruating women. When compared to other modes of P administration, the area under the curve during the first eight hours was twice as high with the rectal route. With 50 and 100 mg P given sublingually and 100 and 200 mg ingested as tablets, peak levels and area under the curve were twice as high with the higher dosage. The response was more sustained with the higher dosage. All subjects exhibited a significant increase in serum P levels over baseline that persisted for at least eight hours. P levels were still increased over baseline at 24 hours in all subjects after the administration of 100-mg vaginal and rectal suppositories and 200-mg tablets. These findings are in general agreement with previous reports showing that luteal phase serum P concentrations can be reached easily with non-parenteral modes of administering micronized P and that oral P administration could become an attractive alternative to the currently used oral mode of administering synthetic progestins.
A progesterone solution was administered by intravaginal instillation, intramuscular injection, and sublingually to estrogen-deficient women, with or without estradiol (E2) replacement, and serum progesterone (P) concentrations were measured by radioimmunoassay. Intravaginal application to postmenopausal subjects receiving E2 gave the highest values of serum P: 10 times baseline at 15 minutes and 30 to 40 times at 1 to 2 hours, with sustained levels, for 7 hours and decline to 10 times baseline at 24 hours. Intravaginal application to hypoestrogenic women gave similar results, but of much lower magnitude (highest value, 20 times baseline). Intramuscular injection, in contradistinction, showed gradually increasing levels over the study period, up to 30 times basal values at 24 hours. It contrast, sublingual application produced very modest serum increases, to approximately 10 times baseline within 2 hours and return to basal value at 24 hours. Since the most rapid and highest levels were observed by vaginal application to postmenopausal women receiving estrogen, and considering that the vagina has been similarly shown to be very effective for estrogen absorption, it is conceived that full hormone replacement could be accomplished in the deficient states by cyclic vaginal application of both steroids.
To determine pharmacokinetic and endometrial effects of vaginally delivered micronized P. Functionally agonadal estrogen-replacement recipients received either micronized P administered vaginally or bi-daily IM injections of P. Hourly blood samples were obtained, from baseline to 6 hours after the initial dose of P and again on simulated cycle day 21 when transvaginal ultrasound (US) measurements and tissue samples of the endometrium were performed. Blood and tissue samples were assayed for P. Endometrial histology, estrogen receptor (ER) and P receptor (PR) contents were evaluated. University of Southern California School of Medicine, Los Angeles, California. Twenty functionally agonadal and four normally ovulating women. Delivery differences were assessed by [1] endometrial P concentrations; [2] USs; [3] histologic datings; [4] ER and PR contents, and [5] serum P levels. Endometrial P concentrations were higher with vaginally administered P than endometrial concentrations observed in normal ovulatory women or women who consistently had the highest serum P after IM administration (11.50 +/- 2.60 versus 1.40 +/- 0.40 versus 0.30 +/- 0.10 ng/mg protein [36.56 +/- 8.27 versus 4.45 +/- 1.27 versus 0.95 +/- 0.32 nmol/L], respectively). After 7 days of P, no differences between either treatment regimen and control groups were detected by histologic, ultrasonographic, or immunocytochemical receptor analyses. Vaginal micronized P enhances P delivery to the uterus compared with a standard IM regimen and results in a synchronous secretory endometrial histology in agonadal women preparing for embryo donation.
Progesterone (P) has not been administered orally because of reportedly poor bioavailability and a rapid clearance rate. Unfortunately, the synthetic derivatives, although orally active, have a number of disadvantages and fail to mimic natural P completely. To investigate the bioavailability and short-term toxicity of oral micronized P, a standardized dose of 200 mg of micronized P was administered to nine healthy postmenopausal women and one male subject. Serial determinations of serum P concentrations demonstrated rapid absorption of P. Peak concentrations of P rose from a negligible baseline level to 17.0 +/- 4.9 ng/ml at an average of 2.8 +/- 0.35 hours after administration. The peak concentrations of P were equivalent to those observed in the midluteal phase in normal control cycles (14.1 +/- 2.7 ng/ml). All subjects exhibited significant elevation of P over baseline levels that persisted for at least 6 hours after the single oral dose and returned to initial levels by 24 hours. There was no significant change in estradiol, follicle-stimulating hormone, luteinizing hormone, cortisol, aldosterone, lipids, or hepatic enzymes during the 24-hour study interval.
PMID 11392023 11392023 Stanczyk et al. 1999, Stanczyk 1999
Cite this article
Stanczyk, F. Z. (1999). Pharmacokinetics of progesterone administered by the oral and parenteral routes. The Journal of Reproductive Medicine, 44(2 Suppl), 141-147.
Stanczyk FZ. Pharmacokinetics of progesterone administered by the oral and parenteral routes. J Reprod Med. 1999;44(2 Suppl):141-147.
Stanczyk, F. Z. "Pharmacokinetics of progesterone administered by the oral and parenteral routes." The Journal of Reproductive Medicine, vol. 44, no. 2 Suppl, 1999, pp. 141-147.
03taz7m60