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Hormone Therapy for Women

Structural differences exist between human, synthetic, and animal hormones. In order for a replacement hormone to fully replicate the function of hormones that 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. Natural hormones include estrogens, progesterone, testosterone, dehydroepiandrosterone (DHEA), and natural thyroid hormones. Our compounding pharmacists work with patients and practitioners to provide customized hormone therapy with the needed hormones in the most appropriate strength and dosage form to meet each woman’s specific needs. Hormone 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 adjustments are essential.

The Value of Compounded Bioidentical Hormone Therapy

After the results of the Women’s Health Initiative trials were first published in 2002, patient and professional interest in potential options to conventional hormone therapy grew, and the number of prescriptions for compounded hormones (cBHT) significantly increased.

Compounding is the preparation of a custom formulation of a medication to fit a patient’s unique needs which cannot be met with commercially available products. Estrogens, progesterone, and testosterone have been widely used and clinically accepted internationally since the 1940s, both as manufactured products and compounded preparations. Millions of women rely on bioidentical hormones for menopausal issues, fertility challenges, and other hormonal imbalances, and men benefit from therapy as well.

Even though there have been dozens of hormone-containing commercially-available products evaluated for safety and efficacy, there is still a need for individual compounded preparations for millions of patients. Compounding permits the dose, dosage form, and route of administration to be customized and titrated to obtain the desired clinical effect in each individual patient while minimizing any potential side effects. This is why so many patients prefer cBHT as compared to manufactured products available only in limited dosage forms and strengths.

Many, if not most, patients have already tried commercially-available products without the desired clinical response and so they change to cBHT. These patients have a significant therapeutic need and often compliance and outcomes can improve with customized medications.

Rethinking Hormone Replacement

The North American Menopause Society (NAMS) released its 2017 Hormone Therapy Position Statement, which has been endorsed by 52 agencies including the American Association of Clinical Endocrinologists, the American Women’s Medical Association, the Society of Obstetricians and Gynaecologists of Canada, and supported as an educational tool by the American College of Obstetricians and Gynecologists (ACOG). To quote the statement: “Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM) and has been shown to prevent bone loss and fracture. The risks of HT differ depending on type, dose, duration of use, route of administration, the timing of initiation, and whether a progestogen is used. Treatment should be individualized to identify the most appropriate HT type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing HT. For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome VMS and for those at elevated risk for bone loss or fracture. For women who initiate HT more than 10 or 20 years from menopause onset or are aged 60 years or older, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS or bone loss, with shared decision-making and periodic reevaluation. For bothersome GSM symptoms not relieved with over-the-counter therapies and without indications for use of systemic HT, low-dose vaginal estrogen therapy or other therapies are recommended.”

Menopause. 2017 Jul;24(7):728-753.

The 2017 hormone therapy position statement of The North American Menopause Society.

Click here to access the PubMed abstract of this article.

The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women aged 50 to 59 years.

Findings from the Women’s Health Initiative (WHI) published in 2002 indicated a greater risk of breast cancer and coronary heart disease among women who used a combination of estrogen and progestin as menopausal hormone replacement therapy. In the WHI study arm that investigated the use of estrogen alone (no progestin in women who had hysterectomies), there was a decrease in the risk of breast cancer and heart disease, and a lower rate of mortality in comparison with women who received a placebo.The backlash from widely publicized findings frightened many women and some physicians, and the use of hormone replacement therapy precipitously declined. Sarrel et al. of the Yale University School of Medicine, Yale University School of Public Health and University of Florence (Italy) Department of Public Health examined the effect of estrogen avoidance on mortality rates. They derived a formula to relate the excess mortality among hysterectomized women aged 50 to 59 years assigned to placebo in the WHI randomized controlled trial to the entire population of comparable women in the United States, incorporating the decline in estrogen use observed between 2002 and 2011. They calculated that a minimum of 18,601 and as many as 91,610 postmenopausal women died prematurely because of the avoidance of estrogen therapy. “Sadly, the media, women, and health care providers did not appreciate the difference between the two kinds of hormone therapy,” commented lead researcher Philip Sarrel, MD. “As a result, the use of all forms of FDA-approved menopausal hormone therapy declined precipitously.” He concluded that informed discussion between the women and their health care providers about the effects of hormone therapy is a matter of considerable urgency. “Essentially, estradiol inhibits the development of atherosclerosis and helps maintain normal arterial blood flow.”

Am J Public Health. 2013 Sep;103(9):1583-8

Click here to access the PubMed abstract of this article.

In September, 2017, Manson et al. published an observational follow-up of approximately 98% of the 27,347 postmenopausal women aged 50-79 who were enrolled in two WHI randomized clinical trials between 1993 and 1998 and followed up through 2014. They concluded that among postmenopausal women, hormone therapy with estrogen plus progestin for a median of 5.6 years or with estrogen alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.

JAMA. 2017 Sep 12;318(10):927-938.

Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials.

Click here to access the PubMed abstract of this article.

Arefa Cassoobhoy, MD, MPH, a senior medical correspondent for Medscape, interviewed JoAnn Manson, MD, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital in Boston, and lead author of the WHI. Dr. Manson shared the following perspectives:

For women (below age 60) and closer proximity to onset of menopause (within 10 years), the absolute risks of heart disease, stroke, deep venous thrombosis (DVT), and breast cancer, related to hormone therapy, are lower.
Women who are at greater risk for and have a higher frequency of hot flashes and night sweats are more likely to derive quality-of-life benefits from hormone therapy. Thus, the benefit-risk ratio becomes much better because of the lower absolute risk and the greater likelihood of deriving quality-of-life benefits.
Transdermal hormone therapy has the advantage of avoiding first-pass liver metabolism, and therefore it’s less likely to increase clotting protein or triglyceride levels and avoids some of the other concerns associated with the oral route of administration. The observational studies suggest that the risks for DVT, pulmonary embolism, and possibly even stroke are lower with the transdermal than the oral route. As of yet, there are no large-scale randomized trials doing direct head-to-head comparisons.
The risk for cardiovascular events, both heart disease and stroke, will be greater in older women. If you are going to use hormone therapy in women who are more distant from the onset of menopause or who have significant risk factors such as diabetes or hypertension, it is preferable to go with the low-dose transdermal formulation rather than oral hormone therapy.
In contrast to the vasomotor symptoms (hot flashes and night sweats), genitourinary symptoms actually progress over time. About 50% of women are seriously affected by these symptoms in terms of decreased quality of life, poor sexual health, and discomfort with sexual activity. Genitourinary conditions and also are associated with urinary tract infections and physical health. These symptoms are undertreated and under-recognized, and clinicians should ask about them because many women are very uncomfortable bringing up the subject. Low-dose vaginal estrogen is the most effective treatment and does not increase the blood level of estrogen above the usual postmenopausal range. In terms of the evidence base and the clinical trial data, there is no evidence of an increased risk for heart disease, stroke, DVT, dementia, or breast cancer with low-dose vaginal estrogen.
Women with early menopause (either premature ovarian insufficiency or early surgical menopause)—who have an increased risk for heart disease, cognitive decline, bone loss, and osteoporosis – are particularly good candidates for hormone therapy.
The WHI observational follow-up urges caution when considering initiating hormone therapy at an older age in women with diabetes, as these women are at the greatest risk for cognitive decline.

NAMS’ New Hormone Therapy Position Statement: Clinical Takeaways

//www.medscape.com/viewarticle/88408

REASONS FOR CHOOSING COMPOUNDED MEDICATIONS INCLUDE:

Patient allergies or failure to respond to commercial products
Adverse reactions to commercial preparations. For example, if a patient has a reaction to an adhesive on a patch, we can compound the needed medication as a transdermal cream.
Need for a dose or dosage form that is not commercially available. For example, transdermal and vaginal creams may offer potential advantages because non-oral administration bypasses first-pass hepatic metabolism.

Our compounding pharmacy puts patient safety first by adhering to current regulations and compounding medications using pure ingredients from FDA-inspected facilities.

Androgens ↓

Androgens are hormones that are important to the integrity of skin, muscle, and bone in both males and females, and have an important role in maintaining libido. Declines in serum testosterone are associated with hysterectomy, menopause, and age-related gender-independent decreases in DHEA and DHEA-sulfate. DHEA (dehydroepiandrosterone) is an androgen precursor from which the body can derive testosterone. After menopause, a woman’s ovaries continue to produce androgens; however, the majority of the androgens produced in the female body, even before menopause, come from peripheral conversion of DHEA. As the body ages, production of DHEA declines so that by the time a woman goes through menopause, the production of DHEA is often inadequate. Additionally, ERT may cause relative ovarian and adrenal androgen deficiency, creating a rationale for concurrent physiologic androgen replacement. Recently, attention has turned to the addition of the androgens to a woman’s HRT regimen in order to alleviate recalcitrant menopausal symptoms and further protect against osteoporosis, loss of immune function, obesity, and diabetes.

Androgens, such as testosterone and DHEA:

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

Progesterone ↓

Progesterone is a term that is incorrectly used interchangeably to describe both progesterone which is “chemically identical” to what the body naturally produces and synthetic derivatives. Synthetic progestins are analogues of progesterone and have been developed because they are patentable, more potent, and have a longer duration. Medroxyprogesterone acetate, the most commonly used synthetic progestin, was shown in a large study to cause significant lowering of HDL “good” cholesterol, thereby decreasing the cardioprotective benefit of estrogen therapy. Side effects are a frequent cause for discontinuation of HRT. Only about 20% of women who start synthetic HRT remain on it two years later.

Progesterone:

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

The benefits of progesterone are not limited to the prevention of endometrial cancer in women who are receiving estrogen replacement. Progesterone therapy is not only needed by women who have an “intact uterus”, but is also valuable for women who have had a hysterectomy. Vasomotor flushing is the most bothersome complaint of menopause and is the most common reason women seek HRT and remain compliant. For over 40 years, estrogens have been the mainstay of treatment of hot flashes, but progesterone may be effective as well.

Progesterone for Brain and Bone Health

Progesterone (P4), a well-known neurosteroid, is produced by ovaries and placenta in females and by adrenal glands in both sexes. Progesterone also has multiple non-reproductive functions and is synthesized by central nervous system (CNS) tissues to perform various vital neurological functions in the brain.

Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation.

In the central nervous system, progesterone helps to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. A substantial body of experimental evidence from animal models documents the neuroprotective role of progesterone in various CNS injury models, including ischemic stroke. Extensive data have revealed that progesterone elicits neuroprotection through multiple mechanisms and systems in an integrated manner to prevent neuronal and glial damage, thus reducing mortality and morbidity. Progesterone has been described as safe for use at the clinical level through different routes in several studies.

Progesterone alone or in combination with estradiol therapy may improve the quality of life for a postmenopausal woman, whether or not she has an intact uterus. In addition to mitigating or preventing vasomotor symptoms or postmenopausal bone loss, oral progesterone causes drowsiness and can be administered at bedtime as part of an HRT regimen, and in this way can help with sleep.

Journal of Osteoporosis Volume 2010, Article ID 845180.

Progesterone and Bone: Actions Promoting Bone Health in Women

Click here to view the 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.

Front Neuroendocrinol. 2008 May; 29(2):313-39.

Progesterone receptors: form and function in the brain

Click here to access the PubMed abstract of this article.

J Environ Pathol Toxicol Oncol. 2017; 36(3):191-205.

Neurosteroids and Ischemic Stroke: Progesterone a Promising Agent in Reducing the Brain Injury in Ischemic Stroke

Click here to access the PubMed abstract of this article.

Estrogens ↓

Estrogens actually refer to a group of related hormones, each with a unique profile of activity. Under normal circumstances, a woman’s circulating estrogen levels fluctuate based on her menstrual cycle. For Hormone Replacement Therapy, these hormones are often prescribed in combination to re-establish a normal physiologic balance. The three main estrogens produced in female humans are:

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

Estrogen, Cardiovascular Health, & Sexual Function ↓

The Kronos Early Estrogen Prevention Study (KEEPS) was designed to address gaps in understanding the effects of timely menopausal hormone treatments (HT) on cardiovascular health and other effects of menopause after the premature termination of the Women’s Health Initiative (WHI).

The Kronos Early Estrogen Prevention Study (KEEPS) was a randomized, double-blinded, placebo-controlled trial to test the hypothesis that initiation of hormone therapy (HT) in healthy, recently postmenopausal women (n = 727) would slow the progression of atherosclerosis. After 4 years, there were no severe adverse effects, including venous thrombosis. Several ancillary studies demonstrated reduced hot flashes, improved sleep, and maintenance of bone mineral density. Sexual function improved with transdermal 17β-estradiol (t-E2). There were no significant effects on cognition, breast pain, or skin wrinkling. KEEPS and its ancillary studies have supported the value and safety of the use of HT in recently postmenopausal women and provide a perspective for future research to optimize HT and the health of postmenopausal women. The KEEPS continuation study continues to pursue these issues.

Transdermal estradiol treatment was associated with a significant increase in mean lubrication and decreased pain compared with placebo. Transdermal estradiol treatment resulted in fewer women with low sexual function compared with placebo, while oral conjugated equine estrogens (CEE) produced no significant benefit.

Menopause. 2019 Sep;26(9):1071-1084.

The Kronos Early Estrogen Prevention Study (KEEPS): what have we learned?

Click here to access the PubMed abstract of this article.

JAMA Intern Med. 2017 Oct 1;177(10):1471-1479

Effects of Oral vs Transdermal Estrogen Therapy on Sexual Function in Early Postmenopause: Ancillary Study of the Kronos Early Estrogen Prevention Study (KEEPS)

Click here to access the PubMed abstract of this article.

Compounded Hormone Therapy for Postmenopausal Women

The Women’s Health Initiative (WHI) was “a large-scale, prospective, blinded, randomized-controlled trial designed to provide evidence regarding use of hormone treatment to prevent cardiovascular disease in menopausal women. The results of the WHI dramatically changed clinical practice, negatively impacted funding for hormone research, and left scientists to unravel the ‘why’ of the results. Now over a decade and a half since the initial publication of the WHI results, basic and clinical scientists often do not interpret the results of the WHI with the precision needed to move the science forward.”

The misuse of the WHI data is based on major misconceptions. The conclusion from the WHI stating ‘this regime’ of hormone product specifically referred to 0.625 mg daily oral CEE + 2.5 mg daily MPA but has been applied to all formulations of estrogen and progestogens, including [transdermal] 17β-estradiol… and natural progesterone.”

Am J Physiol Heart Circ Physiol. 2017 Nov 1;313(5):H1013-H1021.

An update on hormone therapy in postmenopausal women: mini-review for the basic scientist

Click here to access the PubMed abstract of this article.

Robert D. Langer, MD, MPH, one of the WHI investigators, notes: “Key lessons from the WHI are that the effects of HRT on most organ systems vary by age and time since last physiologic exposure to hormones and that there are differences between regimens. In the years since the first WHI report, we have learned much about the characteristics of women who are likely to benefit from HRT. The range of HRT regimens has also increased. Not all women have indications for HRT, but for those who do and who initiate within 10 years of menopause, benefits are both short-term (vasomotor, dyspareunia), and long-term (bone health, coronary risk reduction). Critically, the ‘facts’ that most women and clinicians consider in making the decision to use, or not use, HRT are frequently wrong or incorrectly applied.”

Climacteric. 2017 Apr;20(2):91-96.

The evidence base for HRT: what can we believe?

Click here to access the PubMed abstract of this article.

Many women seek treatment to alleviate menopausal vasomotor symptoms, and use combination compounded hormone therapy to achieve the benefits of estrogen/progesterone for endometrial protection.

Expert Rev Clin Pharmacol. 2019 Aug;12(8):729-739.

A combined, bioidentical, oral, 17β-estradiol and progesterone capsule for the treatment of moderate to severe vasomotor symptoms due to menopause

Click here to access the PubMed abstract of this article.

Hormone therapy initially consisted of estrogens alone and progestogens were secondly added to estrogens for preventing the risk of endometrial cancer associated to estrogens use. “It is now well known that oral and transdermal estrogens are differentially associated with VTE risk. The choice of progesterone versus a synthetic progestogens may be another important determinant of the thrombotic risk among hormone users. Both randomized controlled trials and meta-analyses of observational studies have suggested that the VTE risk was higher among users of estrogens plus progestogens than among users of estrogens alone. With respect to the different pharmacological classes of progestogens, there is evidence for a deleterious effect of medroxy-progesterone acetate on VTE risk. In addition, observational studies showed that norpregnane derivatives were significantly associated with an increased VTE risk whereas micronized progesterone could be safe with respect to thrombotic risk.”

Maturitas. 2011 Dec;70(4):354-60.

Progestogens and venous thromboembolism among postmenopausal women using hormone therapy

Click here to access the PubMed abstract of this article.

Estrogen Therapy may reduce the risk of diabetes in postmenopausal women

It is known that younger women are less likely than men to develop type 2 diabetes. But after menopause, the trend reverses dramatically and women are at higher risk of diabetes due to declining levels of estrogens, specifically, estradiol, which exerts specific actions on the pancreas and insulin biosynthesis and secretion. Clinical and experimental data from research done at University Hospital/Diabetes Center and University of Geneva Medical School, Geneva, Switzerland indicate a beneficial effect of estrogens on energy and glucose homeostasis associated with improved insulin sensitivity. Dr. Sandra Handgraaf noted: “A number of scientists are working on the effect of estrogens on pancreatic insulin-producing cells. But its effect on glucagon-producing cells, another hormone regulating blood sugar, had never been explored before… Besides their pivotal role in sexual development and reproduction, estrogens prevent the occurrence of visceral obesity, insulin resistance, and glucose intolerance in women.” Study leader Jacques Philippe, MD, a Harvard University/Mass General Hospital-trained endocrinologist, said: “It is important to remember hormonal substitution, when taken at the beginning of menopause and for a few years only, does not cause any particular risk of cardiovascular events.” The study concluded that a woman receiving hormone replacement therapy is up to 35 percent less likely to develop type 2 diabetes.

JCI Insight. 2018;3(7):e98569.

17-β Estradiol regulates proglucagon-derived peptide secretion in mouse and human α- and L cells

Click here to access the PubMed abstract of this article.

Quality of life and sexual function of naturally postmenopausal women on an ultralow-concentration E3 vaginal gel

Vaginal E3 gel (0.005%) therapy significantly improves the trophism of the vaginal mucosa and the sexual health and QoL of naturally postmenopausal women. These results confirm that low doses of vaginal estrogen must be considered as the first choice for the initial treatment of postmenopausal genitourinary symptoms.

Menopause. 2016 Jan;23(1):47-54.

Click here to access the PubMed abstract of this article.

Micronized progesterone for vasomotor symptoms

Researchers concluded that oral micronized progesterone is effective for the treatment of hot flushes and night sweats in healthy women early in postmenopause.

Menopause. 2012 Aug; 19(8):886-93

Oral micronized progesterone for vasomotor symptoms–a placebo-controlled randomized trial in healthy postmenopausal women

Click here to access the PubMed abstract of this article.

Vasomotor Symptoms (VMS) Progesterone Study: Vasomotor Symptoms and Endothelial Function – Trial of Oral Micronized Progesterone

Click here to access more information about this case study.

Androgen treatment of postmenopausal women

Testosterone is physiologically important for women. Serum testosterone levels decline with age, with the most precipitous fall being prior to menopause. There is no level of testosterone that defines a woman as being testosterone deficient. However, there is substantial, high-quality evidence to support the use of testosterone for the treatment of hypoactive sexual desire disorder in postmenopausal women. Preliminary data suggests testosterone has favorable effects on bone and muscle mass, cognitive function, and the cardiovascular system.

J Steroid Biochem Mol Biol. 2014 Jul; 142:107-14.

Click here to access the PubMed abstract of this article.

Risk of Breast Cancer by Type of Menopausal Hormone Therapy: a Case-Control Study among Post-Menopausal Women in France

This study confirms differential effects on breast cancer risk of progestagens and regimens specifically used in France. Formulation of EP therapies containing natural progesterone was not associated with increased risk of breast cancer but may poorly protect against endometrial cancer.

PLoS ONE 2013;8:e78016.

Click here to view the article.

Progesterone receptor could slow breast cancer growth

Up to half of the women with breast cancer could benefit from taking progesterone, after research discovers how it modulates the actions of the oestrogen receptor. More clinical trials are necessary to test whether giving women with ER/PR double-positive breast cancer progesterone, alongside oestrogen-blocking drugs, helps more women survive this disease.

Pharmaceutical Journal, 2015 Jul 17; 14:53.

Click here to view the article.

Progesterone receptor modulates estrogen receptor-α action in breast cancer

Progesterone receptor (PR) expression is employed as a biomarker of estrogen receptor-α (ERα) function and breast cancer prognosis. We now show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited estrogen-mediated growth of ERα+ cell line xenografts and primary ERα+ breast tumour explants and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PgR is a common feature in ERα+ breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions.

Nature. 2015 Jul 16; 523(7560): 313–317.

Click here to view the article.

The 2017 hormone therapy position statement of The North American Menopause Society

The risks of HT differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized to identify the most appropriate HT type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing HT.

Menopause. 2017 Jul;24(7):728-753.

Click here to access the PubMed abstract of this article.

Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women’s Health Initiative Randomized Trials

Among postmenopausal women, hormone therapy with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.

JAMA. 2017 Sep 12;318(10):927-938.

Click here to access the PubMed abstract of this article.

The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women aged 50 to 59 years.

Estrogen therapy (ET) in younger postmenopausal women is associated with a decisive reduction in all-cause mortality, but estrogen use in this population is low and continuing to fall. Informed discussion between these women and their health care providers about the effects of ET is important and necessary.

Am J Public Health. 2013 Sep;103(9):1583-8.

Click here to access the PubMed abstract of this article.

Quality of life and costs associated with micronized progesterone and medroxyprogesterone acetate in hormone replacement therapy for nonhysterectomized, postmenopausal women.

Natural micronized progesterone (MP) is a clinically effective, well-tolerated, and cost-comparable alternative to medroxyprogesterone acetate (MPA).

Clin Ther. 2001 Jul;23(7):1099-115.

Click here to access the PubMed abstract of this article.

Sleep in menopause: differential effects of two forms of hormone replacement therapy.

The study suggests that medroxyprogesterone acetate (MPA) and micronized progesterone (MP) are both effective for treating menopausal symptoms but that MP may better improve the quality of sleep in postmenopausal women taking estrogen.

Menopause. 2001 Jan-Feb;8(1):10-6.

Click here to access the PubMed abstract of this article.

Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study

These findings of this study suggest that the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone or dydrogesterone.

Breast Cancer Res Treat 2008;107:103–11.

Click here to view the article.

Pilot study: absorption and efficacy of multiple hormones delivered in a single cream applied to the mucous membranes of the labia and vagina.

This study is the first to document systemic absorption of multiple hormones by both saliva and blood as well as improvement of health-related quality of life. The therapy was generally well-tolerated with only 2 patients experiencing minor irritation, but they continued therapy. Additional studies in larger numbers of patients will provide better knowledge for clinicians wanting to provide similar therapy at the lowest effective dose.

Gynecol Obstet Invest. 2008;66(2):111-8.

Click here to access the PubMed abstract of this article.

Dr. Kent Holtorf is a leading authority in the field of hormone replacement therapy and is also a board examiner for the American Board of Anti-Aging Medicine (ABAAM).

Click here to read Dr. Holtorf’s article about the benefits of customized hormone therapy.

VTE and CVD Complications in Menopausal Women Using Transdermal Versus Oral Estrogen Therapy

The risk of venous thromboembolism (VTE) and cardiovascular disease (CVD) complications were evaluated and healthcare costs were assessed in menopausal women using an estradiol transdermal system versus oral estrogen therapy (ET). It was determined that transdermal ET users incurred lower adjusted all-cause and VTE/CVD-related healthcare costs relative to oral ET users and transdermal users also incurred lower healthcare costs.

Menopause: June 2016 – Volume 23 – Issue 6 – p 600–610

Click here to access the abstract of this article.

Menopausal Hormone Therapy and Mortality

A systematic review and meta-analysis of 43 randomized clinical trials concluded there were no significant associations between use of menopausal hormone-replacement therapy and all-cause mortality. No significant associations were found between hormone use and mortality due to myocardial infarction, breast cancer, or stroke. When analyzed separately, there were also no associations with risks for death from cancers of the lung, ovary, or colon/rectum. Results were similar for estrogen-only therapy and for combined estrogen-progesterone therapy.

ENDO 2015: The Endocrine Society Annual Meeting. Abstract FRI-125, presented March 6, 2015.

//www.medscape.com/viewarticle/841074 (a Medscape account is needed to view this article)

Global consensus statement on menopausal hormone therapy.

Menopausal hormone therapy is the most effective treatment for symptoms related to the hormonal changes of menopause, such as hot flushes and sleep deprivation. Hormone therapy is also beneficial for bone health and may decrease mortality and cardiovascular disease. Risks associated with menopausal hormone therapy are acknowledged, but benefits derived will generally outweigh the risks for women under 60, or within 10 years of menopause. Taking menopausal hormone therapy is a decision that needs to be individualized, according to a woman’s symptoms, and her individual health history. This decision should be made under the advisement of a qualified physician.

Climacteric. 2013 Apr;16(2):203-4.

Click here to access the PubMed abstract of this article.

After 10 years of treatment, women receiving hormone replacement therapy soon after menopause had a significantly reduced risk of mortality, heart failure, or myocardial infarction, without any apparent increase in the risk of cancer, venous thromboembolism, or stroke.

BMJ 2012;345:e6409

Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial

Click here to access this article.

The study examined the long-term effects of compounded natural transdermal hormones on cardiovascular biomarkers, hemostatic, inflammatory, immune signaling factors; quality of life measures; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care. This model of care warrants consideration for peri/postmenopausal women especially in populations with high perceived stress and a history of stressful life events prior to, or during the menopausal transition.Int J Pharm Compd. 2013 Jan-Feb;17(1):74-85.

The effects of compounded transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women.

Click here to access the PubMed abstract of this article.Testosterone (T) therapy is being increasingly used to treat symptoms of hormone deficiency in pre and postmenopausal women. T is essential for physical and mental health in women. A source of confusion concerning the safety of T therapy in both men and women is the extrapolation of adverse events from high doses of oral and injectable anabolic-androgenic steroids to T therapy, despite a lack of evidence. Testosterone is not masculinizing and does not increase aggression or cause hoarseness. Testosterone increases scalp hair growth, is mood-stabilizing, and is cardiac and breast protective. “Abandoning myths, misconceptions and unfounded concerns about T and T therapy in women will enable physicians to provide evidenced-based recommendations and appropriate therapy.”

Maturitas. 2013 Mar; 74(3):230-4.

Testosterone therapy in women: Myths and misconceptions.

Click here to access the PubMed abstract of this article.

Literature reviewers conclude that oral postmenopausal estrogen replacement is associated with an increased risk for venous thromboembolism. The review did not address transdermal estrogen therapy.

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.

Click here to access the PubMed abstract of this article.

The use of oral estrogen plus progestin hormone therapy in postmenopausal women was associated with doubling the risk of development of venous thrombosis.

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.

Stanczyk et al. of Department of Obstetrics and Gynecology, University of Southern California Keck School of Medicine, report: “antiproliferative effects on the endometrium have been demonstrated with progesterone creams when circulating levels of progesterone are low. Thus, effects of topical progesterone creams on the endometrium should not be based on serum progesterone levels, but on histologic examination of the endometrium. Despite the low serum progesterone levels achieved with the creams, salivary progesterone levels are very high, indicating that progesterone levels in serum do not necessarily reflect those in tissues”

Menopause. 2005 Mar;12(2):232-7.

Percutaneous administration of progesterone: blood levels and endometrial protection.

Click here to access the PubMed abstract of this article.

“These findings suggest that the choice of the progestagen component in combined HRT is of importance regarding breast cancer risk; it could be preferable to use progesterone.”

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.

Click here to access the PubMed abstract of this article.

Ovarian androgens normally protect mammary epithelial cells and the addition of testosterone (not METHYLtestosterone) to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population.

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.

Chang et al. studied the influences of percutaneous administration of estradiol and progesterone on the human breast epithelial cell cycle in vivo and reported that progesterone decreases estrogen-induced breast cell proliferation by 400%.

Fertil Steril. 1995 Apr;63(4):785-91.

Influences of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo.

Click here to access the PubMed abstract of this article.

While none of the hormone treatments used in this study had a detectable effect on mood, Cummings et al conclude “the lesser side effects of the micronized progesterone-containing regimen suggest that some women may prefer it to an MPA-containing regimen.”

Menopause. 2002 Jul-Aug;9(4):253-63.

Comparison of physical and emotional side effects of progesterone or medroxyprogesterone in early postmenopausal women.

Click here to access the PubMed abstract of this article.

“This study demonstrates that the daily administration of a combination of micronized E2 and progesterone results in symptomatic improvement, minimal side effects, an improved lipid profile, and amenorrhea without endometrial proliferation or hyperplasia in menopausal women.”

Obstet Gynecol. 1989 Apr;73(4):606-12.

Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone.

Click here to access the PubMed abstract of this article.

This trial indicates that the use of natural progesterone does not increase the risk of breast cancer, as opposed to synthetic progestins.

Fertil Steril. 1998 May;69(5):963-9.

Estradiol and progesterone regulate the proliferation of human breast epithelial cells.

Click here to access the PubMed abstract of this article.

A growing body of medical literature suggests that various progestogens are not equivalent. Furthermore, trials indicate that the use of natural progesterone alone or combined with estradiol does not increase the risk of breast cancer while the use of medroxyprogesterone acetate or norethisterone acetate stimulates the proliferation of breast cancer cells.

Maturitas. 2003 Dec 10;46 Suppl 1:S55-8.

Differential effects of progestogens on breast cancer cell lines.

Click here to access the PubMed abstract of this article.

Estrogen deficiency during menopause contributes to the development of abdominal obesity and insulin resistance and could represent a major step in the development of diabetes in women. In a 2006 meta-analysis of 107 trials, Salpeter et al. concluded that appropriate HRT reduces abdominal obesity, insulin resistance, new-onset diabetes, lipids, pro-inflammatory adhesion molecules and pro-coagulant factors in women without diabetes.

Diab Obes Metab 2006;8:538–54.

Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women.

Click here to access the PubMed abstract of this article.

Glucose metabolism and insulin sensitivity can be improved by estrogen replacement therapy but the addition of an androgenic progestin, such as MPA or NETA, may reduce the beneficial effect of estrogens. While MPA is known to increase insulin resistance and impair glucose tolerance, natural progesterone does not.

Maturitas 2008;59:249–58.

Effects of estradiol and norethisterone on lipids, insulin resistance and carotid flow.

Click here to access the PubMed abstract of this article.

Neuroprotective effects of progesterone include prevention and reversal of age-dependent changes and dysfunction. Some of these actions, particularly those mediated by conversion to neurosteroids such as allopregnanolone, may not be shared by synthetic progestins since progesterone behaves differently in the brain than synthetic progestins (particularly MPA), through direct effects, as well as indirectly through effects on the vascular endothelium. This may have important implications for the effective use of HRT in the maintenance of neuronal function during menopause and aging and for protection against neurodegenerative diseases.

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.

Click here to access the PubMed abstract of this article.

As women age and estrogen levels decline, cutaneous changes such as dryness, atrophy, fine wrinkling and poor healing occur. This article reviews the effects of declining estrogen levels on the skin and the effects of estrogen supplementation.

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.

Click here to access the PubMed abstract of this article.

Ninety-seven percent of the 189 women participating in this study experienced varying degrees of symptom control, but complications described with traditional HRT did not develop in these patients using customized natural hormones. The findings of this study point out a need for larger controlled trials of customized natural hormones in the management of menopause.

Gynecol Endocrinol. 2010 Feb;26(2):81-5.

Natural Hormone Therapy for Menopause

Click here to access the PubMed abstract of this article.

Transdermal estradiol was similarly effective as raloxifene in preventing bone loss at the lumbar spine, was well tolerated, and had no clinically significant effect on endometrium or breast density.

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.

Click here to access the PubMed abstract of this article.

In this 2005 review of clinical studies comparing synthetic progestins to natural progesterone, Campagnoli et al concluded: “The balance of the in vivo evidence is that progesterone does not have a cancer-promoting effect on breast tissue. …We, therefore, suggest that when HRT is indicated, preparations containing progesterone and not a synthetic progestin should be used, according to a sequential or cyclic-combined regimen. In this way, the risk of endometrial cancer is minimized without increasing the risk of BC [breast cancer].”

J Steroid Biochem Mol Biol. 2005 Jul;96(2):95-108.

Progestins and progesterone in hormone replacement therapy and the risk of breast cancer.

Click here to access the PubMed abstract of this article.

In this 2005 clinical trial, Fournier et al compared synthetic progestins to the natural progesterone and reported: “The risk was significantly greater… with HRT containing synthetic progestins than with HRT containing micronized progesterone, the relative risk being 1.4 and 0.9, respectively.”

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.

Click here to access the PubMed abstract of this article.

This large French study raises the possibility that micronized progesterone when combined with human estrogens, may have less impact on breast cancer mortality.

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.

Click here to access the PubMed abstract of this article.

Transdermal Progesterone and Estrogen Improve Blood Pressure in Menopausal Women with High Stress

Dr. Kenna Stephenson of the University of Texas Health Science Center has shown luteal phase levels of progesterone and estrogen administered via transdermal delivery improve blood pressure in perimenopausal and menopausal women with prehypertension and stress related to work or home.//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, notes: “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.” Differences exist among the exogenous progestogens, which include both natural progesterone and synthetic and semi-synthetic progestins, drugs which are “structurally related – but are not identical – to either progesterone or testosterone… Progesterone and progestins differ not only in their structure, but also in their potency, as determined by standard bioassays… Additionally, studies often do not evaluate the effects of progestogens on specific organs or compare the side-effect profiles of individual agents. These characteristics constitute an important, although rarely 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

Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and oral administration has proven to be inferior to intramuscular (IM) and vaginal routes. Progesterone IM achieves serum progesterone values that are within the range of the luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between IM and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favor the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after IM administration, even if they are lower than those 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 produced by the corpus luteum during the luteal phase. It is absorbed when administered orally but is greater than 90% metabolized during the first hepatic pass. This greatly limits the efficacy of once-daily administration and also results in “unphysiologically” high levels of progesterone metabolites which can cause dizziness and drowsiness to the point of preventing the operation of a motor vehicle. Synthetic progestins, such as medroxyprogesterone acetate and norethindrone acetate, have been specifically designed to resist enzymatic degradation and remain active after oral administration. However, according to Drs. Warren and Shantha of the Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, these synthetic progestins exert undesirable effects on the liver and often cause severe psychological side effects. Transvaginal administration of progesterone is a practical non-oral route available for administering progesterone. Early experience was gained with vaginal suppositories. The clinical acceptance of progesterone administered as a vaginal gel was enhanced by the characteristics of a polycarbophil-based gel, which conveys controlled and sustained-released 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 given in conjunction with physiological amounts of estradiol produces endometrial changes similar to those seen in the luteal phase, despite plasma progesterone levels that remain subphysiologic. Studies in infertility show that vaginal progesterone in this form allows secretory transformation of the endometrium and the development of pregnancy despite providing low systemic progesterone concentrations. Fewer side effects occur when vaginal progesterone is used for hormone replacement than 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 top of the hormone cascade, the “parent hormone” from which neurosteroids and sex hormones are formed, and gives rise to important “neurohormones” that affect learning, memory, mood, sleep, and many other functions.
Pregnenolone may relieve anxiety, help to fight depression, and reduce symptoms of withdrawal from nicotine and alcohol addiction.
Hormone levels naturally decline with advancing age. People with lower pregnenolone levels are more likely to suffer from memory deficits, mood disorders, and even some mental illnesses.
Pregnenolone and other neuroactive steroids can protect brain cells against the long-term damage that can lead to Alzheimer’s disease and other forms of dementia.

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

Pregnenolone has vast 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, allopregnanolone (a pregnenolone metabolite), and DHEA-sulfate (DHEAS) in all the main memory-related areas of their brains, compared with control patients. Furthermore, the brains of patients with the highest neurosteroid levels display the lowest collections of the destructive amyloid-beta proteins. 4,5

Researchers have also shown that pregnenolone increases brain levels of acetylcholine, a key neurotransmitter required for optimal brain function, which is deficient in patients with Alzheimer’s disease.6 Acetylcholine is not only vital for thought and memory, but it is also involved in controlling sleep cycles, especially the phase of sleep that is associated with memory (called paradoxical sleep or the random eye movement [REM] phase).

Neurosteroids are known to affect anxiety in humans.7 Researchers from the University of California in San Francisco performed two studies of pregnenolone and anti-anxiety medications and concluded that pregnenolone, taken as a supplement while using an anti-anxiety medication, could reduce many adverse effects of the medication, such as sedation and memory impairment.8

There is increasing evidence that lower levels of pregnenolone are associated with a variety of mental health conditions beyond anxiety, including depression, phobias, and even schizophrenia.9,10,11,12 One study revealed that schizophrenic patients with the lowest levels of pregnenolone were also most likely to have high levels of anxiety.13

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

Please click on the links below for more information.

//www.lef.org/magazine/mag2007/nov2007_report_pregnenolone_01.htm

Researchers at The University of Texas at Tyler, led by Kenna Stephenson, M.D., showed that use of progesterone in a topical cream (20 mg per day) relieved menopausal symptoms. In addition, in a subpopulation of hypercortisolemic women, nocturnal cortisol levels were reduced to normal range while they were using the progesterone cream as compared to placebo. Stress activates cortisol, and an abnormal cortisol pattern has been associated with an increased risk of heart attacks, cancer, obesity and other diseases.

Blood 2004 Nov; 104(11):16

Progesterone Relieves Menopausal Symptoms and Normalizes Nocturnal Cortisol Levels

The French E3N-EPIC cohort study assessed the risk of breast cancer associated with HRT use in 54,548 postmenopausal women.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.The neuroprotective and promyelinating effects of progesterone are promising not only for preventing but also for reversing, age-dependent changes and dysfunctions.

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.

Clinical evidence shows that, during menopause, estrogen withdrawal gives rise to modifications in mood, behavior and cognition and that estrogen administration is able to improve mood and cognitive efficiency in post-menopause. There may be a critical period of time for HRT-related neuroprotection, and early initiation of estrogen therapy may be necessary for cognitive benefit.

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.

New research from the Women’s Health Initiative Memory Study (WHIMS) links the use of hormone replacement therapy (HRT) before the age of 65 years to a reduced risk of all-cause dementia and Alzheimer’s disease (AD) in women. At the American Academy of Neurology’s 59th Annual Meeting, researchers presented an analysis that showed early HRT use was associated with a 46% overall reduction in dementia risk and a 64% reduction in AD. WHIMS also included 2 studies that looked at cognitive outcomes and HRT in women over 65 years old. At an average 5-year follow-up, both the conjugated equine estrogens plus medroxyprogesterone acetate (CEE + MPA) and the CEE-alone trials showed conjugated estrogens, with or without MPA, increased dementia risk when therapy was initiated after age 65 years. In the CEE + MPA trial the risk doubled, while in the CEE-alone trial there was about a 50% increased risk. There is evidence from animal models suggesting estrogen at an earlier age may be beneficial, and these results are intriguing because they seem to support that evidence.While studies describe the therapies used in the WHI as “estrogen with or without progesterone”, the WHI actually used only synthetic CEE and MPA (which is chemically different than progesterone).

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.

Progesterone Therapy for Catamenial Epilepsy

Catamenial epilepsy refers to seizures that occur or worsen around menstruation. Researchers at North Carolina State University evaluated the hypothesis that neurosteroid “replacement” is an effective and rational therapy for catamenial epilepsy. It is well known that progesterone possesses anticonvulsant properties. The clustering of seizures around the beginning of menstruation corresponds with a significant drop in the levels of progesterone circulating in the body and an increase in the estrogen:progesterone ratio. Recent studies have shown that progesterone is metabolised to the neurosteroid allopregnanolone which plays a crucial role in seizure protection. Declining levels of allopregnanolone, which occur during the menstrual cycle, 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. on days 15 to 28 of the menstrual cycle. In a 3 month investigation of cyclic natural progesterone therapy, 23 of 25 (92%) women continued on the same AED and progesterone protocol and continued to have a very substantial (62% to 74%) reduction in seizure frequency.

Epilepsy Behav. 2008 Jul;13(1):12-24.

The role of sex steroids in catamenial epilepsy and premenstrual dysphoric disorder: implications for diagnosis and treatment.

Click here to access the PubMed abstract of this article.

Adv Biomed Res. 2013 Mar 6;2:8.

Progesterone therapy in women with intractable catamenial epilepsy.

Click here to access the PubMed abstract of this article.

Indian Journal of Pharmacology 2005;37(5):288-293

Pharmacotherapy of catamenial epilepsy

Click here to access this article.

Seizure. 2008 Mar;17(2):176-80.

Hormone replacement therapy: will it affect seizure control and AED levels?

Click here to access the PubMed abstract of this article.

Neurology 1995;45:1660-2

Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group.

Click here to access the PubMed abstract of this article.

Neurology 1999;52:1917-8

Progesterone therapy in women with epilepsy: a 3-year follow-up

Click here to access the PubMed abstract of this article.

The Women’s Health Initiative Memory Study (WHIMS) links the use of hormone replacement therapy (HRT) before the age of 65 years to a reduced risk of all-cause dementia and Alzheimer’s disease (AD) in women.

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.

The following finding that conjugated equine estrogen was associated with venous thrombotic risk may have implications for the choice of hormones in perimenopausal and postmenopausal women.

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.

These observations suggest that the addition of testosterone to conventional hormone therapy for postmenopausal women does not increase and may indeed reduce the hormone therapy-associated breast cancer risk-thereby returning the incidence to the normal rates observed in the general, untreated population.

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.

The pharmacodynamic differences of testosterone and methyltestosterone are briefly reviewed in the context of choice for individualized clinical use.

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.

The results of this study suggest a significant reduction in the incidence of type 2 diabetes in our population of non-obese, healthy postmenopausal women who used transdermal 17-beta-estradiol. This could suggest that, in some women, the estrogen deficiency that occurs after menopause could represent a fundamental step in the process of diabetogenesis.

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: https://care.diabetesjournals.org/content/27/3/645.full

Mayo Clinic researchers surveyed 176 women taking natural micronized progesterone who had previously taken synthetic progestins. After one to six months, the women reported an overall 34% increase in satisfaction on micronized progesterone compared to their previous HRT, reporting these improvements: 50% in hot flashes, 42% in depression, and 47% in anxiety. Micronized progesterone was also more effective in controlling breakthrough bleeding.

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.

Click here 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.

Vaginal progesterone suppositories have also been shown to decrease the rate of preterm birth in patients at increased risk. Da Fonseca et al noted that among 142 women who had one prior preterm birth, prophylactic cerclage, or uterine malformation, daily use of a 100-mg vaginal progesterone suppository compared with placebo significantly decreased the likelihood of delivery prior to 37 weeks.

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.