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Bio-Identical Hormone Replacement Therapy for Women

BHRT or Bio-Identical Hormone Replacement Therapy has many benefits that things such as synthetic hormones do not have. The molecular structure with BHRT is the exact same as the natural hormones that are created in our bodies. This is a replacement therapy that is meant for people that are experiencing major differences in their hormones due to certain things like life style changes, aging, or different diseases. Many different symptoms from hormone imbalances include:

  • Weight Gain
  • Hot Flashes
  • Mood Swings
  • Irregular Menstrual Cycles
  • Reduced Libido
  • Painful Intercourse
  • Infertility
  • Night Sweats
  • PMS
  • Memory Lapses
  • Insomnia
  • Osteoporosis
  • Fibrocystic Breast

Structural differences exist between synthetic, human and animal hormones. For a replacement hormone to completely replicate the hormones function, that were originally produced naturally and present in the body, the chemical structure must be the exact same as the original. There are major differences between hormones that are natural to humans, and horse preparations or synthetic. Side chains can be added to naturally happening hormones to help create a synthetic drug that can be patented by manufacturers. A drug that is patented can be mass produced for a profit, which makes a drug company be able to afford research such as the research to find out the medications effectiveness and use. However substances that are naturally-occuring can’t be patented, so scientific studies are fewer on natural hormones since medical research is usually funded by the drug companies.

Natural hormones include estradiol (E2), estrone (E1),  testosterone, dehydroepiandrosterone (DHEA),  progesterone, and pregnenolone. Our amazing compounding pharmacists work with doctors and patients to provide hormone therapy that is customized to provide the right strength and dosage to meet every specific women’s needs. Hormone therapy should be carefully started after a women’s complete medical and family history has been reviewed by a physician. Every woman will respond to therapy in her own way because every woman is different. Adjustments and close monitoring is very essential.

 Hormone Therapy for Women

Structural differences exist between human, and synthetic and animal hormones. In order for a replacement hormone to fully replicate the function of hormones which were originally naturally produced and present in the human body, the chemical structure must exactly match the original.  There are significant differences between hormones that are natural to humans and synthetic or horse preparations. Side chains can be added to a naturally-occurring hormone to create a synthetic drug that can be patented by a manufacturer. A patented drug can be profitable to mass produce, and therefore a drug company can afford to fund research as to the medication’s use and effectiveness. However, naturally-occurring substances can not be patented, so scientific studies are less numerous on natural hormones, because medical research is usually funded by drug companies.

Natural hormones include estrone (E1), estradiol (E2), progesterone, testosterone, dehydroepiandrosterone (DHEA), and pregnenolone. Our compounding specialists work together with patients and prescribers to provide customized hormone therapy that provides the needed hormones in the most appropriate strength and dosage form to meet each woman’s specific needs. Hormone replacement therapy should be initiated carefully after a woman’s medical and family history has been reviewed. Every woman is unique and will respond to therapy in her own way. Close monitoring and medication adjustments are essential.

 Androgens

Hormones that are important to the integrity of the muscle, skin, and bone in both males and females are called Androgens. Androgens have a very important role in maintaining libido. Decreases in serum testosterone are associated with menopause, hysterectomy, and gender-independant age related  decreases in DHEA-sulfate and DHEA. DHEA (dehydroepiandrosterone) is a precursor for androgen where the body can derive testosterone. After a woman experiences menopause, her ovaries continue to produce these androgens. The majority of the androgens that are produced in the females body come from the peripheral conversion of DHEA. This is true even before menopause. Production of DHEA slows as the body ages, thus when a woman goes through menopause , the DHEA production is often not enough. Also, ERT may cause adrenal androgen deficiency and relative ovarian , which creates a rationale for concurrent physiologic androgen replacement. Quite recently, the addition to androgens to a woman’s HRT regimen  has brought attention. This is in order to subside recalcitrant menopausal symptoms and also protect against loss of immune function, osteoporosis, diabetes, obesity.

DHEA and testosterone androgens:

  • enhance bone building (increase calcium retention).
  • enhance libido
  • improves energy level and mental alertness.
  • provide cardiovascular protection (lower cholesterol).

Research

Numerous studies on hormone replacement therapy (HRT)  have shown a conflict and has raised several serious questions about HRT appropriateness. Hormone replacement is an approved therapy to get relief from moderate up to severe hot flashes and symptoms of vaginal and vulvar atrophy. Several studies have confirmed that estrogen replacement actually decreases the risk if experiencing colon cancer, progesterone and estrogen lower risk of fracture and various hormones enhance libido, and increase energy. Reliable and reputable sources have reports that conflict in regarded to issues like Alzheimer’s disease, stroke, and memory.

Except for the Postmenopausal Estrogen/Progestin Intervention (PEPI) study, major studies have not succeeded in distinguishing among dosages and types of HRT used in the study, or only examined the use of  HRT synthetic preparations as shown in the Women’s Health Initiative or WHI. The WHI study was made to identify potential benefits and risks of HRT. The progestin-esrogen section of the trial was halted in 2002 after results were showing that a synthetic hormone combination that has both conjugated equine estrogens also known as CEE, plus MPA (medroxyprogesterone acetate) increased the risk in women for developing heart disease, invasive breast cancer, pulmonary embolism, and stroke. The safety monitoring board and data decided that the risks outweigh the evidence of benefits for things like colon cancer and fractures.Using data from the aforementioned study, WHI, researchers later came to the conclusion that synthetic CEE plus MPA doesn’t improve mental functioning and even may increase the risk of dementia in ladies age of 65 and over. They suggest that these hormones actually increase the risk if stroke which  we know increases the risk of dementia. Typical HRT users, in regards to the risk of dementia, are in their 50s. The WHI study focused more on women that were age 65 and older, who have a higher risk for dementia. The portion of the WHI study that was the “estrogen-only” portion was stopped in March 2004 after the data was reviewed and suggested that the synthetic CEE by itself, had no impact one way or the other on heart disease but actually may increase the risk of stroke.

Many medical professionals and patients are unaware of the availability of  different alternatives. In reality, women’s experiences and clinical outcomes of HRT differ greatly depending on the dosage form, the dose, and route of administration, and also the type of hormone that’s used. As a result of doubts and concerns that were generated by studies that use synthetic hormones, many women who could greatly and substantially benefit from customized hormone replacement may never get the chance.

Published research laying out the differences between synthetic HRT and natural, is now more ample, but studies of natural HRT will probably never be great and as large as those dealing with patented synthetic hormones. Our pharmacy welcomes any questions you may have.

Estrogens

Estrogens  refers to a section or group of related hormones, each with a very unique profile of activity. Under normal circumstances, a woman’s circulating estrogen levels will change based on her menstrual cycle. For Hormone Replacement Therapy, these hormones are often prescribed by a physician in combination to re-establish a normal and healthy physiologic balance. Three of the main estrogens produced in human females are:

  • E1 (Estrone; 10-20% of circulating estrogens) is the main estrogen produced after menopause.
  • E2 (Estradiol; 10-30% of circulating estrogens) is the major secretory and the most potent product of the ovary, and the predominant estrogen produced before menopause.
  • E3 (60-80% of circulating estrogens)

Progesterone

Progesterone is a term that is not correctly used interchangeably to describe both progesterone which is “chemically identical” to what the body will naturally produce, and synthetic derivatives. Synthetic progestins are analogues of progesterone, and have been developed because they are more potent, patentable, and have a longer duration. The most commonly used synthetic progestin (Medroxyprogesterone acetate), was shown in a large study to cause significant lowering of “good” cholesterol (HDL), thereby lowering the cardioprotective benefit of estrogen therapy. Often HRT is stopped due to side effects. The women that start on synthetic HRT, only about 20% of them continue on it after 2 years.

Supporting Literature

Prim Care. 2008 Dec;35(4):669-705.
Hormones in wellness and disease prevention: common practices, current state of the evidence, and questions for the future.
Schwartz ET, Holtorf K.
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Climacteric. 2003 Sep;6(3):221-7.
Comparison of the proliferative effects of estradiol and conjugated equine estrogens on human breast cancer cells and impact of continuous combined progestogen addition.
vMueck AO, Seeger H, Wallwiener D.
Click here to access the PubMed abstract of this article.

Am J Obstet Gynecol. 1999 Jun;180(6 Pt 1):1480-3.
Serum and tissue hormone levels of vaginally and orally administered estradiol.
Click here to access the PubMed abstract of this article.

Gynecol Obstet Fertil. 2007 May;35(5):388-97. Epub 2007 Mar 27.
[Hormone replacement therapy in postmenopausal women: all the treatments are not the same].
Ribot C, Trémollieres F.
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N Engl J Med. 1975 Dec 4;293(23):1167-70.
Increased risk of endometrial carcinoma among users of conjugated estrogens.
Ziel HK, Finkle WD.
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Fertil Steril. 1998 May;69(5):963-9.
Estradiol and progesterone regulate the proliferation of human breast epithelial cells.
Foidart JM, Colin C, Denoo X, Desreux J, Béliard A, Fournier S, de Lignières B.
Click here to access the PubMed abstract of this article.

Breast Cancer Res Treat. 2008 Jan;107(1):103-11. Epub 2007 Feb 27.
Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.
Fournier A, Berrino F, Clavel-Chapelon F.
Click here to access the PubMed abstract of this article.

Maturitas. 2003 Dec 10;46 Suppl 1:S59-69.
Progestins and their effects on the breast.
Druckmann R.
Click here to access the PubMed abstract of this article.

Climacteric. 2002 Dec;5(4):332-40.
Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women.
de Lignières B, de Vathaire F, Fournier S, Urbinelli R, Allaert F, Le MG, Kuttenn F.
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Am J Obstet Gynecol. 1985 Aug 15;152(8):1092-9.
A double-blind comparative study of Estraderm and Premarin in the amelioration of postmenopausal symptoms.
Place VA, Powers M, Darley PE, Schenkel L, Good WR.
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Am J Obstet Gynecol. 1987 Jan;156(1):61-5.
The effect of percutaneous estradiol and natural progesterone on postmenopausal bone loss.
Riis BJ, Thomsen K, Strøm V, Christiansen C.
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J Clin Endocrinol Metab. 1991 Aug;73(2):373-9.
Changes in plasma lipoprotein and apolipoprotein composition in relation to oral versus percutaneous administration of estrogen alone or in cyclic association with utrogestan in menopausal women.
Moorjani S, Dupont A, Labrie F, De Lignieres B, Cusan L, Dupont P, Mailloux J, Lupien PJ.
Click here to access the PubMed abstract of this article.

JAMA. 1995 Jan 18;273(3):199-208.
Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.
The Writing Group for the PEPI Trial.
Click here to access the PubMed abstract of this article.

J Am Coll Cardiol, 2000; 36:2154-2159
Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women
Giuseppe M. C. Rosano, MD, FACC*, Carolyn M. Webb, PhD, Sergio Chierchia, MD, FACC*, Gian Luigi Morgani, MD*, Michele Gabraele, MD*, Phillip M. Sarrel, MD, Dominique de Ziegler, MD and Peter Collins, MD, FACC
Click here to access the PubMed abstract of this article.

JAMA. 2002 Jul 17;288(3):321-33.
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial.
Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women’s Health Initiative Investigators.
Click here to access the PubMed abstract of this article.

Menopause. 2000 Nov-Dec;7(6):395-401.
Effects of estradiol with and without testosterone on body composition and relationships with lipids in postmenopausal women.
Davis SR, Walker KZ, Strauss BJ.
Click here to access the PubMed abstract of this article.

J Clin Endocrinol Metab. 2002 Apr;87(4):1509-16.
Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in postmenopausal women.
Dobs AS, Nguyen T, Pace C, Roberts CP.
Click here to access the PubMed abstract of this article.

Int J Cancer. 2005 Apr 10;114(3):448-54.
Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort.
Fournier A et al.
Click here to access the PubMed abstract of this article.

JAMA. 2010 Oct 20;304(15):1684-92.
Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women.
Chlebowski RT et al.
Click here to access the PubMed abstract of this article.

Lancet. 2003 Aug 9;362(9382):419-27.
Breast cancer and hormone-replacement therapy in the Million Women Study.
Beral V; Million Women Study Collaborators.
Click here to access the PubMed abstract of this article.

J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108.
Progestins and progesterone in hormone replacement therapy and the risk of breast cancer.
Campagnoli C, Clavel-Chapelon F, Kaaks R, Peris C, Berrino F.
Click here to access the PubMed abstract of this article.

J Clin Oncol. 2008 Mar 10;26(8):1260-8.
Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer.
Fournier A et al.
Click here to access the PubMed abstract of this article.

J Womens Health Gend Based Med. 2000 May;9(4):381-7.
Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey.
Fitzpatrick LA, Pace C, Wiita B.
Click here to access the PubMed abstract of this article.

Gynecol Endocrinol. 2010 Feb;26(2):81-5.
Natural hormone therapy for menopause.
Mahmud K.
Click here to access the PubMed abstract of this article.

Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1516-21. Epub 2004 May 27.
Effects of conventional or lower doses of hormone replacement therapy in postmenopausal women.
Koh KK et al.
Click here to access the PubMed abstract of this article.

Maturitas. 2008 Jul-Aug;60(3-4):185-201. Epub 2008 Sep 5.
Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review.
L’hermite M, Simoncini T, Fuller S, Genazzani AR.
Click here to access the PubMed abstract of this article.

Ann Intern Med. 2002 May 7;136(9):680-90.
Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the U.S. Preventive Services Task Force.

Miller J, Chan BK, Nelson HD.
Click here to access the PubMed abstract of this article.

JAMA. 2004 Oct 6;292(13):1573-80.
Estrogen plus progestin and risk of venous thrombosis.
Cushman M, Kuller LH, Prentice R, Rodabough RJ, Psaty BM, Stafford RS, Sidney S, Rosendaal FR; Women’s Health Initiative Investigators.
Click here to access the PubMed abstract of this article.

Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3071-8.
Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial.
Scarabin PY, Alhenc-Gelas M, Plu-Bureau G, Taisne P, Agher R, Aiach M.
Click here to access the PubMed abstract of this article.

JAMA. 1995 Jan 18;273(3):199-208.
Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.
The Writing Group for the PEPI Trial.
Click here to access the PubMed abstract of this article.

Permeation of steroids through human skin.
Johnson ME, Blankschtein D, Langer R.
Click here to access the PubMed abstract of this article.

Menopause. 2005 Mar;12(2):232-7.
Percutaneous administration of progesterone: blood levels and endometrial protection.
Stanczyk FZ, Paulson RJ, Roy S.
Click here to access the PubMed abstract of this article.

Breast Cancer Res Treat. 2008 Jan;107(1):103-11. Epub 2007 Feb 27.
Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.
Fournier A, Berrino F, Clavel-Chapelon F.
Click here to access the PubMed abstract of this article.

Menopause. 2004 Sep-Oct;11(5):531-5.
Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy.
Dimitrakakis C, Jones RA, Liu A, Bondy CA.
Click here to access the PubMed abstract of this article.

Fertil Steril. 1995 Apr;63(4):785-91.
Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.
Chang KJ, Lee TT, Linares-Cruz G, Fournier S, de Ligniéres B.
Click here to access the PubMed abstract of this article.

J Womens Health Gend Based Med. 2000 May;9(4):381-7.
Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey.
Fitzpatrick LA, Pace C, Wiita B.
Click here to access the PubMed abstract of this article.

Menopause. 2002 Jul-Aug;9(4):253-63.
Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women.
Cummings JA, Brizendine L.
Click here to access the PubMed abstract of this article.

Obstet Gynecol. 1989 Apr;73(4):606-12.
Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone.
Hargrove JT, Maxson WS, Wentz AC, Burnett LS.
Click here to access the PubMed abstract of this article.

Fertil Steril. 1998 May;69(5):963-9.
Estradiol and progesterone regulate the proliferation of human breast epithelial cells.
Foidart JM, Colin C, Denoo X, Desreux J, Béliard A, Fournier S, de Lignières B.
Click here to access the PubMed abstract of this article.

Maturitas. 2003 Dec 10;46 Suppl 1:S55-8.
Differential effects of progestogens on breast cancer cell lines.
Franke HR, Vermes I.
Click here to access the PubMed abstract of this article.

Diab Obes Metab 2006;8:538–54.
Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women.
Salpeter SR, Walsh JME, Ormiston TM, Greyber E, Buckley NS, Salpeter EE.
Click here to access the PubMed abstract of this article.

Maturitas 2008;59:249–58.
Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow.
Fernandes CE, Pompei LM, Machado RB, Ferreira JA, Melo NR, Peixoto S.
Click here to access the PubMed abstract of this article.

Endocr Rev. 2007 Jun;28(4):387-439. Epub 2007 Apr 12.
Novel perspectives for progesterone in hormone replacement therapy, with special reference to the nervous system.
Schumacher M, Guennoun R, Ghoumari A, Massaad C, Robert F, El-Etr M, Akwa Y, Rajkowski K, Baulieu EE.
Click here to access the PubMed abstract of this article.

Womens Health Issues. 2005 Jul-Aug;15(4):187-95.
After the Women’s Health Initiative: decision making and trust of women taking hormone therapy.
Schonberg MA, Davis RB, Wee CC.
Click here to access the PubMed abstract of this article.

J Am Acad Dermatol. 2005 Oct;53(4):555-68
Estrogen and skin: the effects of estrogen, menopause, and hormone replacement therapy on the skin.
Hall G, Phillips TJ.
Click here to access the PubMed abstract of this article.

Gynecol Endocrinol. 2009 Aug 19:1-5. [Epub ahead of print]
Natural Hormone Therapy for Menopause
Click here to access the PubMed abstract of this article.

Menopause. 2009 May-Jun;16(3):559-65.
Effect of microdose transdermal 17beta-estradiol compared with raloxifene in the prevention of bone loss in healthy postmenopausal women: a 2-year, randomized, double-blind trial.
Schaefers M, Muysers C, Alexandersen P, Christiansen C.
Click here to access the PubMed abstract of this article.

JAMA. 2010 Oct 20;304(15):1684-92.
Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women.
Chlebowski RT et al; WHI Investigators.
Click here to access the PubMed abstract of this article.

Lancet. 2003 Aug 9;362(9382):419-27.
Breast cancer and hormone-replacement therapy in the Million Women Study.
Beral V; Million Women Study Collaborators.
Click here to access the PubMed abstract of this article.

J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108.
Progestins and progesterone in hormone replacement therapy and the risk of breast cancer.
Campagnoli C, Clavel-Chapelon F, Kaaks R, Peris C, Berrino F.
Click here to access the PubMed abstract of this article.

Int J Cancer. 2005 Apr 10;114(3):448-54.
Breast cancer risk in relation to different types of hormone replacement therapy in the E3N-EPIC cohort.
Fournier A, Berrino F, Riboli E, Avenel V, Clavel-Chapelon F.
Click here to access the PubMed abstract of this article.

J Clin Oncol. 2008 Mar 10;26(8):1260-8.
Use of different postmenopausal hormone therapies and risk of histology- and hormone receptor-defined invasive breast cancer.
Fournier A, Fabre A, Mesrine S, Boutron-Ruault MC, Berrino F, Clavel-Chapelon F.
Click here to access the PubMed abstract of this article.

J Womens Health Gend Based Med. 2000 May;9(4):381-7.
Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey.

Fitzpatrick LA, Pace C, Wiita B.
Click here to access the PubMed abstract of this article.

Dr. Kenna Stephenson of the University of Texas Health Science Center has shown luteal phase levels of estrogen and progesterone administered via transdermal delivery improves blood pressure in menopausal and perimenopausal  women with stress and prehypertension and related to work or home.

http://sanjay-kapur.blogspot.com/2009_09_01_archive.html


Progesterone vs Synthetic Progestins: Clinical Options


James A. Simon, MD, Clinical Professor, George Washington University, Washington, DC, states: “Clinicians have numerous options in selecting a progestogen for the individual patient. The specific properties of progesterone or synthetic progestins may result in differing side-effect profiles for individual patients. Route of administration also offers differing systemic or local effects that should be considered for some uses and specific patients.”  Some differences do exist among the exogenous progestogens, which includes both  synthetic and semi-synthetic progestins and natural progesterone, drugs which are “structurally related – but are not the exact same – to either testosterone or progesterone. Progestins and progesterone not only differ in their potency but also their structure, as determined by standard bioassays. Also, studies many times don’t compare the side-effect profiles of individual agents or evaluate the effects of progestogens on specific organs. These characteristics constitute an important, although very seldom discussed, aspect of the differences among progestogens.”

The Journal of Family Practice 2007 Feb; 2(7):S3-S5

Comparison of Different Routes of Progesterone Administration for Luteal Phase Support in Infertility Treatment

Natural progesterone supplementation’s different routs have been tried as luteal phase support in infertility treatments. Orally given progesterone is quickly  metabolized in the gastrointestinal tract and oral administration has proven to be inferior to vaginal routes and intramuscular (IM). Progesterone IM achieves serum progesterone values that are within the range of luteal phase. This results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between vaginal progesterone and IM has led to controversial results in regards to which is better than the other in inducing secretory endometrial transformation. Although, there is increasing evidence in literature to favor the use of vaginal progesterone. Progesterone that is administered vaginally achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on what formulation was used. After application of vaginal progesterone, discrepancies have been found between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those that were observed after IM administration, even if they are in fact lower than those that were  observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.

Hum Reprod Update. 2000 Mar-Apr;6(2):139-48.
Comparison between different routes of progesterone administration as luteal phase support in infertility treatments.
Click here to access the PubMed abstract of this article.

Uses of Progesterone in Clinical Practice

Progesterone is the natural progestogen that is produced by the corpus luteum during the luteal phase. It’s absorbed when taken orally, but is metabolized greater than 90%  during the first hepatic pass. This greatly reduces the efficacy of once a day administration and also results in “unphysiologically” high levels of progesterone metabolites which can cause drowsiness and dizziness to the point of keeping you from operating a motor vehicle. Synthetic progestins, such as norethindrone acetate and medroxyprogesterone acetate, have been specifically engineered to resist enzymatic degradation and remain active after being taken orally. According to Drs. Warren and Shantha of the Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, these synthetic progestins exert unwanted effects on the liver and often cause severe side effects such as psychological side effects. Transvaginal administration of progesterone is a non-oral, practical route that is available when administering progesterone. Vaginal suppositories was used to gain early experience. The clinical acceptance of administering progesterone as a vaginal gel was enhanced by the characteristics of a polycarbophil-based gel, which conveys sustained-released and controlled properties. Investigations have shown that because of local direct vagina-to-uterus transport, which results in a preferential uterine uptake of progesterone, progesterone vaginal gel that is given in conjunction with physiological amounts of estradiol produces endometrial changes  very similar to those that are seen in the luteal phase, despite plasma progesterone levels that remain subphysiologic. Studies in infertility show that vaginal progesterone in this form also allows secretory transformation of the endometrium and the development of pregnancy despite providing minimal systemic progesterone concentrations. When vaginal progesterone is used for hormone replacement, fewer side effects occurs than how many are typically encountered with progestins and oral progesterone.

Int J Fertil Womens Med. 1999 Mar-Apr;44(2):96-103
Uses of progesterone in clinical practice.
Click here to access the PubMed abstract of this article.

Pregnenolone – The Parent Hormone Affecting Memory, Sleep, Anxiety, and Mood


• Pregnenolone is at the very top of the hormone cascade, the “parent hormone” from which sex hormones and neurosteroids are formed, and gives rise to important “neurohormones” that affect memory, mood, learning, sleep, and other functions as well.

• Pregnenolone may help to fight depression,  relieve anxiety, and even reduce symptoms of withdrawal from nicotine and alcohol addiction.
• Hormone levels naturally decline due to getting older. People with lower pregnenolone levels are more likely to suffer from mood disorders, mental illnesses, and even memory deficits.
• Pregnenolone and other neuroactive steroids can protect brain cells against the damage that is long term that can lead to dementia and even Alzheimer’s disease.

The conversion of cholesterol to pregnenolone constitutes the first of the steps in the synthesis of some of the body’s important hormones, including testosterone, dehydroepiandrosterone (DHEA),  estrogen, progesterone, and cortisol. Pregnenolone’s metabolites fulfill a myriad of important and necessary roles in the body, from stimulating memory via excitatory pathways to even relieving anxiety through inhibitory mechanisms.1,2

Pregnenolone has great potential for maintaining healthy cognitive function and may be “the most potent memory enhancer yet reported.”3 Alzheimer’s disease patients have lower levels of pregnenolone,DHEA-sulfate (DHEAS), and allopregnanolone (a pregnenolone metabolite) in all of the main areas of their brains related to memory compared with control patients. The brains of patients that have the highest neurosteroid levels actually display the lowest collections of the destructive amyloid-beta proteins. 4,5,6

Researchers have even shown that pregnenolone improves brain levels of acetylcholine, a key neurotransmitter required for the best and most optimal brain function, which is deficient in patients with Alzheimer’s disease. 7 Acetylcholine is not only vital for memory and thought, it is also involved in controlling sleep cycles, specifically the part of sleep phases that is associated with memory (called paradoxical sleep or the random eye movement [REM] phase).

Neurosteroids are known to affect anxiety in humans.8 Researchers from the University of California in San Francisco performed 2 studies of anti-anxiety medications and pregnenolone and concluded that pregnenolone, taken as a supplement while using a antianxiety medication, could lower many negative  effects of the medication, such as memory impairment and sedations. 9

Increasing evidence shows that lower levels of pregnenolone are associated with a bunch of mental health conditions beyond anxiety, including phobias, depression, and even schizophrenia.10,11,12,13 One study showed that schizophrenic patients that had the lowest levels of pregnenolone were also the most likely to have anxiety in high levels.14

Pregnenolone and other neurosteroids have also been shown to counteract the anxiety-like behavior that is associated with morphine and/or nicotine withdrawal, due to their potent effects on sigma receptors, and may offer relief  or a solution to people that are seeking to overcome these addictions. 15,16

For more information, please click on the following links.
http://www.lef.org/magazine/mag2007/nov2007_report_pregnenolone_01.htm
Pharmacol Biochem Behav. 2006 Aug;84(4):555-67.
Jpn J Pharmacol. 1999 Oct;81(2):125-55.
Proc Natl Acad Sci USA. 1995 Nov 7;92(23):10806-10.
Prog Neurobiol. 2003 Sep;71(1):3-29.
J Clin Endocrinol Metab. 2002 Nov;87(11):5138-43.
Biol Psychiatry. 2006 Dec 15;60(12):1287-94.
Prog Neurobiol. 2003 Sep;71(1):43-8.
Neuropsychobiology. 2004;50(1):6-9.
Psychoneuroendocrinology. 2004 May;29(4):486-500.
10 Prog Neuropsychopharmacol Biol Psychiatry. 2005 Feb;29(2):169-92.
11 Neuropsychopharmacology. 2005 Jun;30(6):1181-6.
12 Pharmacol Biochem Behav. 2006 Aug;84(4):644-55.
13 Am J Psychiatry. 2002 Jan;159(1):145-7.
14 Eur Neuropsychopharmacol. 2007 Apr;17(5):358-65.
15 J Pharmacol Sci. 2006 Feb;100(2):93-118.
16 Brain Res Brain Res Rev. 2001 Nov;37(1-3):116-32.
At The University of Texas at Tyler, researchers led by Kenna Stephenson, M.D., showed that using progesterone in a topical cream (20 mg per day) relieved symptoms of menopause. Also, in a subpopulation of hypercortisolemic women, nocturnal cortisol levels were lowered to range that was considered normal while they were using the progesterone cream as compared to the placebo. Cortisol is activated by stress, and an abnormal pattern of cortisol has been associated with an increased risk of cancer, obesity, heart attacks, and other diseases.

Blood 2004 Nov; 104(11):16
Progesterone Relieves Menopausal Symptoms and Normalizes Nocturnal Cortisol Levels

Breast Cancer Res Treat. 2008 Jan;107(1):103-11
Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study.
Click here to access the PubMed abstract of this article.

Endocr Rev. 2007 Jun;28(4):387-439.
Novel perspectives for progesterone in hormone replacement therapy, with special reference to the nervous system.
Click here to access the PubMed abstract of this article.

Hum Reprod Update. 2007 Mar-Apr;13(2):175-87
Estrogen, cognition and female ageing.
Click here to access the PubMed abstract of this article.

J Clin Endocrinol Metab. 2006 Jan;91(1):136-44.
Pharmacokinetics of Testosterone Gel in Healthy Postmenopausal Women
Click here to access the PubMed abstract of this article.

Absorption and Efficacy of Multiple Hormones Delivered in a Single Cream
Gynecol Obstet Invest. 2008 Apr 29;66(2):111-118.
Click here to access the PubMed abstract of this article.

HRT Before Age 65 May Decrease Risk of Dementia and Alzheimer’s Disease
American Academy of Neurology 59th Annual Meeting: Abstract S31.004. April 28 – May 5, 2007
Click here to access the Medscape article. (accessed January 13, 2012)

Progesterone Therapy for Catamenial Epilepsy

Seizures that occur or worsen around menstruation are known as catamenial epilepsy. North Carolina State University researchers evaluated the hypothesis that neurosteroid “replacement” is an rational and a effective therapy for catamenial epilepsy. It’s well known that progesterone possesses anticonvulsant properties. The gathering or clustering of seizures around the beginning of menstruation corresponds with a drastic drop in the levels of progesterone that are circulating in the body and an increase in the progesterone:estrogen ratio. Studies recently have shown that progesterone is metabolized to the neurosteroid allopregnanolone which plays a pivotal role in seizure protection. Declining levels of allopregnanolone can occur during the menstrual cycle and can provoke seizures.

“Cyclic natural progesterone use has been demonstrated as an effective treatment for catamenial and non-catamenial seizures in women. Progesterone is efficiently absorbed after oral administration as lozenges, and rectal administration as suppositories.” Progesterone was given at 100 to 200 mg, t.i.d. (three times daily) on days 15 to 28 of the menstrual cycle. In a 90 day investigation of cyclic natural progesterone therapy, 23 out of 25 (92%) women continued on the same AED and progesterone protocol and had a very substantial (62% to 74%) reduction in seizure frequency.

Epilepsy Behav. 2008 Mar 16 [Epub ahead of print]
Click here to access the PubMed abstract of this article.

Seizure. 2008 Mar;17(2):176-80.
Click here to access the PubMed abstract of this article.

Indian Journal of Pharmacology 2005; 37(5):288-293
Click here to access this article.

Neurology 1995;45:1660-2
Click here to access the PubMed abstract of this article.

Neurology 1999;52:1917-8
Click here to access the PubMed abstract of this article.American Academy of Neurology 59th Annual Meeting: Abstract S31.004.

April 28 – May 5, 2007

Click here to read a Medscape article on this topic.

JAMA. 2004 Oct 6;292(13):1581-7
Esterified estrogens and conjugated equine estrogens and the risk of venous thrombosis.
Click here to access the PubMed abstract of this article.

Menopause. 2004 Sep-Oct;11(5):531-5
Breast cancer incidence in postmenopausal women using testosterone in addition to usual hormone therapy.
Click here
 to access the PubMed abstract of this article.

Mayo Clin Proc. 2004 Apr;79(4 Suppl):S8-13
Hot flashes and androgens: a biological rationale for clinical practice.
Click here
 to access the PubMed abstract of this article.

Diabetes Care. 2004 Mar;27(3):645-9
Transdermal 17-beta-estradiol and risk of developing type 2 diabetes in a population of healthy, nonobese postmenopausal women.
The full text article is available FREE online: http://care.diabetesjournals.org/cgi/content/full/27/3/645

J Womens Health Gend Based Med 2000 May;9(4):381-7
Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey.
Click here
 to access the PubMed abstract of this article.

Fertil Steril 1999 Sep;72(3):389-97
Micronized progesterone: clinical indications and comparison with current treatments.
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 to access the PubMed abstract of this article.

J Am Coll Cardiol 2000 Dec;36(7):2154-9

Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women. (This is not a “claim”, it is the title of the article.) 
Click here to access the PubMed abstract of this article.

N Engl J Med 2003;348:2379-85
Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate.
Click here to access the PubMed abstract of this article.

Am J Obstet Gynecol 2007;196:224.e1-224.e4.
Increased recurrence of preterm delivery with early cessation of 17-alpha-hydroxyprogesterone caproate.
Click here to access the PubMed abstract of this article.

Am J Obstet Gynecol. 2003; 188(2):419-424.
Prophylactic administration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: a randomized placebo-controlled double-blind study.
Click here to access the PubMed abstract of this article.

Other related articles:

Obstet Gynecol 2005 May;105(5 Pt 1):1128-35

Am J Obstet Gynecol. 2007 May;196(5):453.e1-4
The PEPI Trial, a 3-year multicenter, randomized, double-blind, placebo-controlled study of 875 healthy postmenopausal women, stated that synthetic progestins partially negate the beneficial effects on cholesterol levels that result from taking estrogen. Natural progesterone maintained the benefits of estrogen on cholesterol without side effects.

JAMA 1995 Jan 18;273(3):199-208
Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. 
The Writing Group for the PEPI Trial.
Click here to access the PubMed abstract of this article.

J Reprod Med 2000 Mar;45(3 Suppl):245-58
Rationale for hormone replacement therapy in atherosclerosis prevention.
Click here to access the PubMed abstract of this article.

J Clin Endocrinol Metab 2002;87:1062-1067
Estrogen status correlates with the calcium content of coronary atherosclerotic plaques in women.
Click here
 to access the PubMed abstract of this article.

J Neurosci. 2003 Dec 10;23(36):11420-6
Estradiol attenuates programmed cell death after stroke-like injury.
Click here
 to access the PubMed abstract of this article.

Endocrinology 2001 Mar 1;142(3):969-973
Minireview: Neuroprotective Effects of Estrogen-New Insights into Mechanisms of Action.
Click here
 to access the PubMed abstract of this article.

JAMA. 2004 Oct 6;292(13):1573-80
Estrogen plus progestin and risk of venous thrombosis.
Click here to access the PubMed abstract of this article.

Chem Res Toxicol 1998 Sep;11(9):1105-11
The equine estrogen metabolite 4-hydroxyequilenin causes DNA single-strand breaks and oxidation of DNA bases in vitro.
Click here
 to access the PubMed abstract of this article.

Nat Med 1997 Mar;3(3):324-7
Medroxyprogesterone interferes with ovarian steroid protection against coronary vasospasm.
Click here
 to access the PubMed abstract of this article.

J Reprod Med 1999 Feb;44(2 Suppl):180-4
Progestogens and cardiovascular disease. A critical review.
Click here to access the PubMed abstract of this article.Endocr Rev 1990 May;11(2):386-98

Progesterone as a bone-trophic hormone.
Click here to access the PubMed abstract of this article.

JAMA. 2002 Jul 17;288(3):321-33
Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial.
Click here to access the PubMed abstract of this article.

JAMA 2003 May 28;289(20):2663-72
Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial.
Click here
 to access the PubMed abstract of this article.

JAMA 2003 May 28;289(20):2673-84
Effect of estrogen plus progestin on stroke in postmenopausal women: the Women’s Health Initiative: a randomized trial.
Click here
 to access the PubMed abstract of this article.

Progesterone:

  • is very often prescribed for perimenopausal women to counteract “estrogen dominance” which occurs when a woman produces smaller than normal amounts of progesterone relative to estrogen levels.
  • combined with estrogen, or alone, may improve Bone Mineral Density.
  • can minimize the risk of endometrial cancer in women that are receiving estrogen.
  • is preferred by those women who had previously taken synthetic progestins.

The benefits of progesterone are not limited to just the prevention of endometrial cancer in women who are receiving estrogen replacement. Progesterone therapy is not just needed by women who have an “intact uterus”,  but can also be very valuable for women who have had a hysterectomy. Vasomotor flushing is the most irritating complaint of menopause, and is reason that is most common that women seek HRT and remain compliant. Estrogens have vein the staple of treatment of hot flashes for over 40 years. Another effective treatment may be progesterone.