Progesterone info, as requested

Re: Progesterone info, as requested

• DavezWife member

  August 2009

  I spoke too soon.... this just in from medical mind and literature

   

  The oral route goes through the liver first and is metabolized down before it gets to the uterus so the blood levels will be lower for the same dose oral vs. vaginally.  There are commercially available gels and vaginal inserts intended to be given vaginally and suppositories have been compounded for years by pharmacies.  The dose of the oral is higher though to account for the metabolism (ex. 90mg vs. 200mg).  So giving the same dose vaginally,  will amount to more delivered to the uterus.  I would talk to your dr. to make sure it would not be too much depending on your baseline levels.   

   

   

  Absorption

  A)  Bioavailability

  1)  Oral, capsule: unknown (Prod Info Prometrium(R), 99).

  a)  In an open-label, randomized, parallel-group study, 12 healthy postmenopausal women received one dose of either 90 milligrams of progesterone gel (Crinone(R) 8%) or 100 milligrams oral progesterone capsule (Prometrium(R)). Oral progesterone resulted in much lower bioavailability compared to the vaginal progesterone gel due to its extensive hepatic metabolism (Levine & Watson, 2000).
  b)  Progesterone vaginal gel undergoes a uterine pass effect as demonstrated by high uterine tissue progesterone concentrations after vaginal administration. In a randomized and open study, 14 postmenopausal, healthy women undergoing transabdominal hysterectomies, received 3 doses of either Crinone (R) 8% gel (90 milligrams) or progesterone 50 milligrams intramuscularly (IM) prior to surgery. Baseline serum progesterone levels were collected in the morning the day before surgery. Endometrial progesterone concentrations were obtained from the uterine walls after removal of the uterus. The ratios of endometrial to serum progesterone concentrations were significantly higher (p less than 0.005) in women who received the vaginal progesterone compared to IM progesterone (14.1 median and 1.2 median, respectively). This data suggests that discrepancies between endometrial effects and relatively low serum progesterone levels are due to preferential delivery of progesterone to the uterus. (Cicinelli et al, 2000).
  c)  In spite of the high degree of metabolism and first pass effect, oral PROGESTERONE does result in detectable serum levels. Oral administration of PROGESTERONE 100 mg at 9 AM and 200 mg at 9 PM for 5 days in 5 postmenopausal women produced average PROGESTERONE serum levels of 7.14 ng/mL (22.7 nmol/L) at 10 AM and 15 ng/mL (47.7 nmol/L) at 10 PM (Padwick et al, 1986). Oral administration of PROGESTERONE may be helpful in cases where other routes of administration cannot be used.
  d)  The oral bioavailability of PROGESTERONE may be increased by micronizing the PROGESTERONE powder and administering it in a oil base (Hargrove et al, 1989). After oral administration of 50 mg of micronized PROGESTERONE in oil, the mean serum level was 30.3 ng/mL; compared to 13.2 ng/mL with micronized PROGESTERONE in a plain capsule or 9.6 ng/mL with plain milled PROGESTERONE in a plain capsule.

  2)  Intramuscular, injection: rapidly (Gilman et al, 1990).

  a)  PROGESTERONE in oil is rapidly absorbed after intramuscular injection (Gilman et al, 1990). In one study, intramuscular PROGESTERONE 100 mg/day produced serum PROGESTERONE levels 5 times higher than levels produced by vaginal administration of 300 or 600 mg/day (Devroey et al, 1989).
  b)  In one study intramuscular PROGESTERONE 100 mg/day produced serum PROGESTERONE levels 5 times higher than levels produced by vaginal administration of 300 or 600 mg/day (Devroey et al, 1989). However, the vaginal route of administration was adequate to produce a secretory endometrium.

  3)  Nasal, ointment: well absorbed (Steege et al, 1986).

  a)  After intranasal administration of 20 or 30 mg PROGESTERONE the time to peak serum levels were 30 and 240 minutes respectively in 8 healthy women in the follicular phase of the menstrual cycle. The peak levels for the 20 or 30-mg dose were 2.5 and 4.1 ng/mL respectively. The data for the 30-mg PROGESTERONE dose was skewed by 2 women who had delayed and high absorption (Steege et al, 1986).
  b)  PROGESTERONE was well absorbed when administered by nasal spray (11.2 milligrams PROGESTERONE) to 10 healthy menopausal women (Cicinelli et al, 1991). The average maximum serum level was 3.75 ng/mL, and levels of greater than 2 ng/mL were maintained for 6 hours, returning to baseline after 12 hours. An unpleasant aftertaste was reported by all study subjects. Greater convenience of the nasal spray may be preferred over the use of a nasal ointment.

  4)  Transdermal progesterone (40 mg per day) increased serum progesterone to a small extent (mean Cmax after 42 days of use, 5.3 nmol/L). The achieved serum levels of progesterone are lower than those achieved with vaginal progesterone gel or oral micronized progesterone at doses sufficient to induce secretory transformation of endometrium (Carey et al, 2000).
  5)  Vaginal, 4% and 8% gel: 27.6% and 19.8% after single dose, respectively (Prod Info Crinone(R), 2000).

  a)  Progesterone absorption with Crinone(R) is prolonged due to its sustained- release properties. The absorption half-life is 25 to 50 hours compared to an elimination half-life of 5 to 20 minutes. This suggests the pharmacokinetic profile of Crinone(R) is dependent on absorption rather than elimination (Prod Info Crinone(R), 2000).
  b)  The time to maximum progesterone concentration after multiple doses of the 4% or 8% gel ranges from 3.55 +/- 2.48 hours to 7.00 +/- 2.88 hours. In addition, the average serum concentration over 24 hours ranges from 4.05 +/- 2.85 nanograms per deciliter (ng/dL) to 11.6 +/- 3.47 ng/dL (Prod Info Progesterone USP, 2000).
  c)  In an open-label, randomized, parallel-group study, 12 healthy postmenopausal women received one dose of either 90 milligrams of progesterone gel (Crinone(R) 8%) or 100 milligrams oral progesterone capsule (Prometrium(R)). The vaginal progesterone gel resulted in greater bioavailability with less relative variability than oral progesterone (Levine & Watson, 2000).

  6)  Vaginal, suppository: to a greater extent than oral route (Kimzey et al, 1991).

  a)  A single-dose study of eight healthy, normally cycling women demonstrated that vaginal administration of 300 milligrams of micronized PROGESTERONE in a NONLIQUEFYING BASE produced sustained serum levels far higher than the same dose of micronized PROGESTERONE given orally (average 13.9 ng/mL versus 1.9 ng/mL at 24 hours, respectively) (Kimzey et al, 1991). Minimal vaginal discharge was reported by study subjects.

    Effects of Food

  1)  Food increases the relative bioavailability (including extent of absorption and maximum plasma concentration, but not rate of absorption) of orally administered micronized progesterone (de Lignieres, 1999; Fitzpatrick & Good, 1999; Prod Info PROMETRIUM(R), 2004).

   

   

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• MrsP71506

  August 2009

  Wow!! Thanks for all the info.  I really appreciate it. 
  

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