Progesterone application methods

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Progesterone application methods are many and varied and include the following...

  • injections
  • IV transfusions
  • subcutaneous implants
  • suppositories/pessaries
  • vaginal tablet
  • troches/lozenges
  • buccal drops
  • oral caps
  • gels
  • oils and creams

Injections are large and therefore painful. They generally contain peanut or sesame oil. The progesterone might crystallise out if the temperature drops too low, heating it gently will reverse this. Each injection is between 50-100mg.

IV transfusions are used for Traumatic Brain Injury. It's a fast, effective means of delivering progesterone in an emergency situation. As the process has been patented there is no way of finding out the contents of the solution. But judging by the success of the system, it does work and causes no harm

Subcutaneous silastic capsules are implants made from a flexible, inert, non-biodegradable silicone elastomer. They can contain 20, 40, 110, or 220 mg of crystalline progesterone. They are characterised by an initial increase in serum hormone levels followed by a decline and then an apparent steady-state that persists from 7 to 24 days post-implant. More commonly they contain a progestin designed to last five years. Biodegradable systems are being developed, which dissolve in the body and do not require removal. Comprising poly(e-caprolactone) or a copolymer of caprolactone and trimethylenecarbonate.

Suppositories/pessaries are very effective, but limited in their application. The ingredients can contain a PEG emulsifier, silica gel, cocoa butter, glycerin, gelatine, water. PEG emulsifiers can contain dioxane, a known carcinogen. The dose ranges from 100mg to 200mg each.

Vaginal tablets are inserted via an applicator, and are also limited in their application. The ingredients can contain lactose monohydrate, polyvinylpyrrolidone, adipic acid, sodium bicarbonate, sodium lauryl sulfate, magnesium stearate, pregelatinized starch, and colloidal silicone dioxide. 100 mg vaginal tablet.

Troches/lozenges are affected by the destruction in the gut and liver, as about 50% is swallowed. Troches can be made from gelatine or a PEG (polyethylene glycol) based emulsifier. PEG emulsifiers can contain dioxane, a known carcinogen. They can contain artificial sweeteners, flavourants, acidulating agents, colourings and preservatives. Troches are a relatively new method of administering bio-identical hormones. The reasoning behind them is the hormone bypasses the stomach and first pass metabolism of the liver as it's absorbed by the buccal mucosa, so entering circulation. Generally 100mg progesterone in each.

Buccal drops share the same fate as either oral or the troches, progesterone is very bitter, so not an option for most women. The progesterone is dissolved in oil, which may be vitamin E, peanut and sesame. Dose is dependant on the number of drops used.

Oral is the least effective route, as much of it is destroyed by the gut and liver. Some of the ingredients are peanut oil, gelatin, glycerin, lecithin, titanium dioxide and various colourants. The cap usually contains 100mg.

Gels are effective, but only used in the vagina. They are applied with a special applicator. The gel is bioadhesive, attaching to the lining of the vagina, accumulation can occur. The vaginal discharge appears as white globules. The ingredients can contain carbomer, phenoxyethanol, caprylyl glycol, sorbic acid, triethanolamine, polyacrylamide, C13-14 isoparaffin, laureth-7, glycerine, vegetable oil, methyl and propylparaben. Dose is dependant on the application, but in the region of 90mg.

Oil is an uncommon form of transdermal delivery, but a few exist as it obviates the need for preservatives. The progesterone might crystallise out if the temperature drops too low, heating it gently will reverse this. The oils may be coconut oil and caprylic/capric triglycerides. Dose is dependant on the amount used.

Creams are regarded by most as the best option. However, a word of caution... take care in reading the ingredients as they can contain harmful substances such as liquid paraffin, parabens, phenoxyethanol, sodium lauryl sulphate, propylene glycol, fragrances, artificial colours and PEG emulsifying waxes, these can contain dioxane, a known carcinogen.

The dose of progesterone is dependant on the amount of the cream used. The strength of the creams vary from 1.5% to 10%.

The progesterone in a cream is absorbed well, and has been found to be as effective as injections and to enter circulation rapidly. Creams have an advantage over all the other systems in that they can be used where and when they are needed...

On painful areas, particularly on the stomach for menstrual cramps, for migraines/headaches, in the vagina for dryness and inflammation or on piles, excellent for burns, on the face where it helps with wrinkles and more.

A progesterone cream can be used anywhere on the body, it does not have to be applied to the thin skinned areas only. The skin comprises 95% kerotinocytes, these have many progesterone receptor sites. Even hair follicles absorb progesterone well.

No special method or applicator is needed to apply a cream, there's no discomfort in using it as in some delivery systems, in fact it often soothes the problem quickly. It can be applied within seconds, on the run if need be.

References

Build up

Gynecol Endocrinol. 2005 Aug;21(2):101-5 A study to look at hormonal absorption of progesterone cream used in conjunction with transdermal estrogen.

Creams and Gels

Drugs Aging. 2008;25(4):269-80
Use of transdermal drug formulations in the elderly

EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS 1998, Vol. 23, No.3, pp. 397--402
Pharmacokinetics of progesterone in postmenopausal women 2. Pharmacokinetics following percutaneous administration

Menopause. 2005 Mar;12(2):232-7 Percutaneous administration of progesterone: blood levels and endometrial protection

Gynecological Endocrinology, Volume 18 , Issue 5May 2004 , pages 240 - 243 High local endometrial effect of vaginal progesterone gel

J Steroid Biochem Mol Biol. 2002 Apr;80(4-5):449-55 Distribution and metabolism of topically applied progesterone in a rat model.

Am J Obstet Gynecol. 1999 Jun;180(6 Pt 1):1504-11 Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

Face

Br J Dermatol. 2005 Sep;153(3):626-34 Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study.

Fatty layer

Menopause. 12(2):232-237, March/April 2005 Percutaneous administration of progesterone: blood levels and endometrial protection.

Gels v Injections

Ther Clin Risk Manag. 2009; 5: 403-407 Luteal Phase Support in assisted reproductive technology treatment: focus on Endometrin® (progesterone) vaginal insert

Medical News Today Article Date: 16 Apr 2008 Vaginal Progesterone Is Equally Effective In Achieving Pregnancy Outcomes As Injectable Progesterone In Donor Egg Cycles

Gels v Tablet insert

Fertil Steril. 2009 Jul 14 Single and multidose pharmacokinetic study of a vaginal micronized progesterone insert (Endometrin) compared with vaginal gel in healthy reproductive-aged female subjects

High dose

The Endocrine Society 92nd Annual Meeting and Expo; June 19- 22, 2010
Progesterone effective for hot flushes, night sweats up to 10 years after final menstruation

J Steroid Biochem. 1984 Jan;20(1):437-9
The effect of progesterone administration on sex hormone binding globulin binding capacity in women with severe premenstrual syndrome

European Journal of Obstetrics & Gynecology and Reproductive Biology Volume 131, Issue 2, April 2007, Pages 182-188 A randomized comparison of side effects and patient convenience between Cyclogest® suppositories and Endometrin® tablets used for luteal phase support in IVF treatment

Acta Obstet Gynecol Scand 2001; 80: 972?973 Substantial relief of myopathic disability by progesterone therapy (A study conducted in Austria found initially 400mg/day, followed a year later by 600mg/day, significantly improved the patients ability to walk. Hers was a very severe case though.)

Human Reproduction, Vol. 14, No. 3, 606-610, March 1999 Pharmacokinetics of natural progesterone administered in the form of a vaginal tablet

Human Reproduction, Vol. 14, No. 8, 1944-1948, August 1999 Luteal support with micronized progesterone following in-vitro fertilization using a down-regulation protocol with gonadotrophin-releasing hormone agonist: a comparative study between vaginal and oral administration

Human Reproduction, Vol. 11, No. 10, pp. 2085-2089, 1996 Endocrinology: Luteal support after in-vitro fertilization: Crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone

Maturitas. 1994 Dec; 20(2-3): 191-8 Endometrial hyperplasia: efficacy of a new treatment with a vaginal cream containing natural micronized progesterone

Human Reproduction, Vol. 8, No. 1, pp. 40-45, 1993 A prospective randomized study on oestradiol valerate supplementation in addition to intravaginal micronized progesterone in buserelin and HMG induced superovulation

Human Reproduction, Vol. 7, No. 2, pp. 168-175, 1992 A prospective randomized comparison of intramuscular or intravaginal natural progesterone as a luteal phase and early pregnancy supplement

Int J Gynaecol Obstet. 1991 May;35(1):61-8 Endometrial responses to various hormone replacement regimens in ovarian failure patients preparing for embryo donation.

IV transfusions

Emory University Jan. 14, 2010
Atlanta To Serve as National Epicenter for Promising Phase III Brain Injury Treatment Trial

Emory University Office of Technology Transfer June 6, 2006
2006 EU Therapeutic Treatment for Traumatic Brain Injury (TBI)

Emory University Press release 02 October 2006
2006 Progesterone Shows Promise as Treatment for Traumatic Brain Injury

ACNR VOLUME 5 NUMBER 4, SEPTEMBER/OCTOBER 2005
2005 Progesterone in the Treatment of Traumatic Brain Injury

Low dose

Gynecol Endocrinol. 2005 Aug;21(2):101-5 A study to look at hormonal absorption of progesterone cream used in conjunction with transdermal estrogen.

Metabolic pass

Expert Review of Obstetrics & Gynecology November 2006, Vol. 1, No. 2, Pages 173-182 Delivery routes of progesterone in assisted reproduction

Menopause. 12(2):232-237, March/April 2005 Percutaneous administration of progesterone: blood levels and endometrial protection

Human Reproduction Update, Vol.6, No.2 pp.139-148, 2000 Comparison between different routes of progesterone administration as luteal phase support in infertility treatments

Human Reproduction, Vol. 11, No. 10, pp. 2085-2089, 1996 Endocrinology: Luteal support after in-vitro fertilization: Crinone 8%, a sustained release vaginal progesterone gel, versus Utrogestan, an oral micronized progesterone

Oral

2000 VCU School of Pharmacy
Progesterone and progestins

Expert Review of Obstetrics & Gynecology November 2006, Vol. 1, No. 2, Pages 173-182 Delivery routes of progesterone in assisted reproduction

Human Reproduction Update, Vol.6, No.2 pp.139-148, 2000 Comparison between different routes of progesterone administration as luteal phase support in infertility treatments

Human Reproduction, Vol. 5, No. 5, pp. 537-543, 1990 Effects of natural progesterone on the morphology of the endometrium in patients with primary ovarian failure

Br Med J (Clin Res Ed). 1983 October 29; 287(6401): 1241-1245 Dose dependent effects of oral progesterone on the oestrogenised postmenopausal endometrium

Skin

Skin Pharmacol. 1994;7(5):237-44
Role of transepidermal and transfollicular routes in percutaneous absorption of steroids: in vitro studies on human skin

Am J Obstet Gynecol. 1999 Jun;180(6 Pt 1):1504-11 Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

Speed of delivery

J Steroid Biochem Mol Biol. 2002 Apr;80(4-5):449-55
Distribution and metabolism of topically applied progesterone in a rat model

Journal of Pharmaceutical Sciences 2006, Volume 66 Issue 12, Pages 1744 - 1748 Progesterone retention by rat uterus I: Pharmacokinetics after uterine intraluminal instillation

Human Reproduction, Vol. 14, No. 3, 606-610, March 1999 Pharmacokinetics of natural progesterone administered in the form of a vaginal tablet

Am J Obstet Gynecol. 1999 Jun;180(6 Pt 1):1504-11 Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen

Subcutaneous silastic capsules

World Health Organization, 1211 Geneva 27, Switzerland Long-acting hormonal contraceptive methods for women

Suppositories

Gynecol Obstet Invest 2004;58:105-108 Pharmacokinetics of Natural Progesterone Vaginal Suppository

Troches

Articles on Complementary Medicine The Truth about Troches

Uterus

Fertil Steril. 1994 Sep;62(3):485-90
Pharmacokinetics and endometrial tissue levels of progesterone after administration by intramuscular and vaginal routes: a comparative study

Menopause. 12(2):232-237, March/April 2005 Percutaneous administration of progesterone: blood levels and endometrial protection.

Gynecological Endocrinology, Volume 18 , Issue 5May 2004 , pages 240 - 243 High local endometrial effect of vaginal progesterone gel

Obstetrics & Gynecology 2000;95:403-406 Direct Transport of Progesterone From Vagina to Uterus

Molecular and Cellular Biology, March 1999, p. 2251-2264, Vol. 19, No. 3 Progesterone Inhibits Estrogen-Induced Cyclin D1 and cdk4 Nuclear Translocation, Cyclin E- and Cyclin A-cdk2 Kinase Activation, and Cell Proliferation in Uterine Epithelial Cells in Mice

Human Reproduction, Vol. 14, No. 3, 606-610, March 1999 Pharmacokinetics of natural progesterone administered in the form of a vaginal tablet

Human Reproduction Update, Vol.5, No.4 pp.365-372, 1999 New Hypotheses. Transvaginal progesterone : evidence for a new functional 'portal system' flowing from the vagina to the uterus

Maturitas. 1994 Dec; 20(2-3): 191-8 Endometrial hyperplasia: efficacy of a new treatment with a vaginal cream containing natural micronized progesterone

Human Reproduction, Vol. 7, No. 2, pp. 168-175, 1992 A prospective randomized comparison of intramuscular or intravaginal natural progesterone as a luteal phase and early pregnancy supplement

Human Reproduction, Vol. 5, No. 5, pp. 537-543, 1990 Effects of natural progesterone on the morphology of the endometrium in patients with primary ovarian failure



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