Hormone menubar
GSE
PROGESTERONE MENUBAR
Delivery route choices for PROGESTERONE: Topical /Epithelial delivery via vagina
Delivery route choices for PROGESTERONE: Topical /Epithelial delivery
via vagina
(Using hormonal cream/gel)
Epithelial tissue forms the covering or lining of all
internal and external body surfaces
Vaginal delivery of
PROGESTERONE is the preferred women.
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.
Vaginal application Progesterone
choices
• 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.
Support for vaginal delivery route
Vaginal route mimics ovarian
PROGESTERONE delivery into blood stream
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
There seems to be a preferential distribution of
PROGESTERONE to the uterus following vaginal
administration
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
Vaginal PROGESTERONE administration
results in a high concentration at the local uterine/endometrial level, despite
generally lower plasma levels than transdermal or intergluteal routes
"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
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. 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. [ PubMed ]
• PROGESTERONE particle
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)
High PROGESTERONE concentration at uterine level has advantages
when supplementing PROGESTERONE for luteal phase support
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 ]
