(Using hormonal cream/gel)
Epithelial tissue forms the covering or lining of all internal and external body surfaces
Particularly when uterine effects need to be maximized or blood concentrations minimized to limit side effects. PROGESTERONE as gel, suppositories or cream is applied to the mucous epithelial membrane lining the vagina. This delivery method avoids "first-pass" liver metabolism problems of oral delivery.
Avoids hormonal build-up in fat cells. This improvement to PROGESTERONE delivery method avoids the hormonal build-up in fat cells that occurs with the transdermal method. Dr. Jonothon Wright, another pioneer in bioidentical hormone supplementation (in addition to the now deceased Dr. John Lee), uses this method in his clinics.
• PROGESTERONE cream rubbed directly on vaginal epithelial membranes. Using finger-tips, it is possible to reach pretty far into the vagina.
• Bio-adhesive gel preparations. These preparations cling to the vaginal membrane, and thus work better than cream formulations and suppositories, which can cause inconvenient vaginal discharges and possibly an irregular absorption of the active component. Sustained release (Gel) forms of PROGESTERONE, alleviate the need for multiple daily treatments.
• Vaginal suppositories/Pessaries. If you can not find these or they are not cost effective, you could make your own by mixing required dose with cocoa butter, which hardens at room temperature, but melts at body temperature. You will need to find some little bullet-shaped molds or use some other ingenious method to shape the suppositories. If only used once per day, it is best used at night (when you are lying down) to prevent gravity-leakage.
Ideally, a woman wants to mimic the way pre-menstrualovaries get hormones directly into the blood stream.
• The ovaries are in the pelvis, and have direct access to the blood stream via a pelvic plexus of veins
• Hormones absorbed through the vaginal membranes also enter the same pelvic plexus of veins emptied into by the ovaries. Hormones are then transported to the heart and lungs and distributed to your tissues just as if your ovary had actually produced them.
Vaginal application closely mimics the body's own hormonal delivery system
Vaginal Plexus
Studies strongly suggest a direct local "portal" for vagina-to-uterus transport of PROGESTERONE . This phenomenon was found to involve the vascular system and confirmed the existence of the so-called "first uterine pass effect".
Cicinelli E, Cignarelli M, Sabatelli S, Romano F, Schonauer LM, Padovano R, Einer-Jensen N. Plasma concentrations of PROGESTERONE are higher in the uterine artery than in the radial artery after vaginal administration of micronized PROGESTERONE in an oil-based solution to postmenopausal women. Fertil Steril. 1998 Mar;69(3):471-3. PubMed
The lymphatic system of the upper part of the vagina, being in direct communication with the lymph vessels of the uterus may also represent a potential route for direct passage to the uterus of substances applied to the vagina.
Transvaginal PROGESTERONE : evidence for a new functional "portal system"flowing from the vagina to the uterus, Human Reprod 1999, Vol 5, No4 pp365-372 PubMed
"First Uterine Pass Effect". The vaginal route is a better choice if the uterus /endometrium is the target area - PROGESTERONE has a direct impact on the uterus before entering circulation (the so-called first uterine pass effect).
Von Eye Corleta H, Capp E, Cardoso Ferreira MB. Pharmacokinetics of natural PROGESTERONE vaginal suppository. Gynecol Obstet Invest 2004;58:105-108.
Alam V, Vega M, Risquez F. Luteal phase support. Reprod Biomed Online 2001;3:250-262.
Weckstein LN, Jacobson A, Galen D, Hampton K, Ivani K, Andres J. Improvement of pregnancy rates with oocytes donation in older recipients with the addition of PROGESTERONE vaginal suppositories. Fertl Steril 1993;60:573-575.
Maddocks S, Hahn P, Moller F, Reid RL. A double-blind placebo- controlled trial of PROGESTERONE vaginal suppositories in the treatment of premenstrual syndrome. Am J Obstet Gynecol 1986;154:573- 581.
de Ziegler D. Hormonal control of endometrial receptivity. Hum Reprod. 1995 Jan;10(1):4-7.
Studies showing that vaginal PROGESTERONE resulted in low serum levels, but efficacious endometrial concentrations. Since PROGESTERONE is absorbed locally, it does not permit high plasma levels of PROGESTERONE , it therefore has less undesirable systemic effects.
• Vaginal gel dose used in the luteal phase at 45mg every 48 hours resulted in low serum PROGESTERONE but endometrial efficacy was unhampered. also, serum PROGESTERONE does not predict effects of vaginal PROGESTERONE on endometrium
Fanchin R, De Ziegler D, Bergeron C, Righini C, Torrisi C, Frydman R. Transvaginal administration of PROGESTERONE . Obstet Gynecol. 1997 Sep;90(3):396-401.[PubMed]
• Miles and coworkers also demonstrated that vaginal administration led to lower serum and higher endometrium PROGESTERONE concentrations compared to measurements after I.M. delivery.
Miles RA, Paulson RJ, Lobo RA, Press MF, Dahmoush L, Sauer MV. Pharmacokinetics and endometrial tissue levels of PROGESTERONE after administration by intramuscular and vaginal routes: a comparative study. Fertil Steril. 1994 Sep;62(3):485-90. [PubMed]
• Gibbons and coworkers compared vaginaland PROGESTERONE delivery in women undergoing egg-donor programs, with higher mean serum PROGESTERONE in I.M. group. All subjects in both groups had an endometrial histology that was "in phase"(meaning the 4 phases, menstrual, proliferative, secretory, and pre-menstrual, of the menstrual cycle were on schedule: ) Vaginal PROGESTERONE delivery has been shown as effective as intramuscular injections for raising endometrial levels and maintaining pregnancy
Gibbons WE, Toner JP, Hamacher P, Kolm P. Experience with a novel vaginal PROGESTERONE preparation in a donor oocyte program.Fertil Steril. 1998 Jan;69(1):96-101. [PubMed]
Vaginal PROGESTERONE absorption may be influenced by the degree of vaginal mucosa estrogen content after estrogen treatment
Villanueva B, Casper RF, Yen SS. Intravaginal administration of PROGESTERONE : enhanced absorption after estrogen treatment. Fertil Steril. 1981 Apr;35(4):433-7. [PubMed]
Vaginal PROGESTERONE absorption may be influenced by the type of the formulation used:
• Different bases of suppositories - tests on glycerinated gelatin, cocoa butter and polyethylene glycol found that they all raised levels above baseline for the same duration, but polyethylene glycol raised the mean peak level of circulating PROGESTERONE the highest.
Price JH, Ismail H, Gorwill RH, Sarda IR.Effect of the suppository base on PROGESTERONE delivery from the vagina.Fertil Steril. 1983 Apr;39(4):490-3 [PubMed]
• PROGESTERONEparticle size. Micronized PROGESTERONE in non-liquefying cream showed promise for a goal of a single daily application
Kimzey LMKimzey LM, Gumowski J, Merriam GR, Grimes GJ Jr, Nelson LM. Absorption of micronized PROGESTERONE from a nonliquefying vaginal cream. Fertil Steril. 1991 Nov;56(5):995-6.[PubMed]
Vaginal PROGESTERONE delivery has been successful for HRT for various conditions
(Warren et al 1999, including menopause (de Zeigler et al, 1999)
E.g. for pregnancy or HRT. Which has the goal of inducing adequate endometrial secretory transformation. Before ovulation, PROGESTERONE levels in a woman's body remain relatively low, but rise after ovulation during the latter part of a woman's menstrual cycle which is called the luteal phase. The luteal phase begins with the production of PROGESTERONE and ends with either pregnancy or menstruation, when the uterus sheds its lining. During pregnancy, PROGESTERONE helps to maintain the lining of the uterus, providing necessary nutrients to support and nurture a fertilized egg.
For pregnancy, the dose amount and timing is crucial. This is because PROGESTERONE may:
(i) Act in favor of implantation as a permissive factor in a certain range of concentration
Or
(ii) Block implantation when its concentrations are lower or higher than cut-off values
Villanueva B, Casper RF, Yen SS. Intravaginal administration of PROGESTERONE : enhanced absorption after estrogen treatment. Fertil Steril. 1981 Apr;35(4):433-7. [PubMed]
Erny R, Simoncini C, Chastclliere N, de Lignres B. Variation de la PROGESTERONE plasmatiquc induites par l'administration vaginale d'Utrogcstan. J Gynecol Biol Reprod 1989; 18:229-234.
E.g. Some of the first contraceptives used a high dose of PROGESTERONE. The timing of the dose should lend support to the natural luteal phase. Penzias et al used Crinone 8%, a vaginal gel containing 90 mg micronized PROGESTERONE in a polycarbophil base, to support luteal phase to support pregnancy after IVF, with rates comparable to intramuscular administration or vaginal suppositories.
Penzias AS, Alpcr MM. Luteal support with vaginal micronized PROGESTERONE gel in assisted reproduction. Reprod Biomed Online 2003;6:287-295. [PubMed]
Anserini P, Costa M, Remorgida V, Sarli R, Guglielminetti E, Ragni N. Luteal phase support in assisted reproductive cycles using cither vaginal (Crinonc 8) or intramuscular (Prontogcst) PROGESTERONE : results of a prospective randomized study. Minerva Ginecol 2001;53:297-301. [PubMed]
Lightman A, KoI S, Itskovitz-Eldor J. A prospective randomized study comparing intramuscular with intravaginal natural PROGESTERONE in programmed thaw cycles. Hum Reprod 1999; 14:2596- 2599.[PubMed]
Vaginal PROGESTERONE Is Equally Effective In Achieving Pregnancy Outcomes As Injectable PROGESTERONE In Donor Egg Cycles. 105 recipients at Boston IVF treated with vaginal PROGESTERONE achieved a 58.1% pregnancy rate and a 51.4% delivery rate, versus a 53.3% pregnancy rate (p=0.503) and a 48.3% delivery rate (p=0.689) for patients receiving intragluteal PROGESTERONE [ Med News Today, 16 Apr 2008]
Commonly used in many countries for luteal support in reproduction-assisted therapies. E.g. for IVF (In vitro fertilization)
Bourgain C, Devroey P, Van Waesberghe L, Smitz J, Van Steirteghem AC, Effects of natural PROGESTERONE on the morphology of the endometrium in patients with primary ovarian failure. Hum Reprod. 1990 Jul;5(5):537-43. [PubMed]
Artini PG, Volpe A, Angioni S, Galassi MC, Battaglia C, Genazzani AR. A comparative, randomized study of three different PROGESTERONE support of the luteal phase following IVF/ET program. J Endocrinol Invest. 1995 Jan;18(1):51-6. [PubMed]
