References/Charts from Can I Speak to the Hormone Lady

 

BEGINNING OF CYCLE (at end of period)

Low E (estrogen) and P (progesterone) in the blood

↓

Low hormone levels sensed by hypothalamus (menstrual control center), which signals the pituitary

↓

Pituitary releases FSH (follicle stimulating hormone) into blood

↓

FSH stimulates follicles in ovary

↓

Follicles produce E

↓

One follicle becomes dominant (others shrink)

↓

Egg inside develops

 

 

OVULATION

Very high Estrogen in blood

↓

Sensed by hypothalamus, signals pituitary

↓

Pituitary releases a surge of LH (luteinizing hormone)

↓

Follicle ruptures, releasing egg

 

 

MENSTRUATION

Sac left behind on ovary = Corpus luteum

↓

Corpus luteum produces estrogen and progesterone

↓

E and P sensed by hypothalamus, signals pituitary

↓

Pituitary decreases production of FSH and LH

↓

E and P production by corpus luteum decreases

↓

Too low hormone to support endometrium, period starts

 

 

PREGNANCY

Fertilized egg begins secreting hCG (human chorionic gonadotropin) when it implants in uterus

↓

HCG supports corpus luteum to continue hormone production, maintains pregnancy until the placenta takes over

 

 

 

 

 

 

 

 

 

APPENDIX I

Progesterone Information

 

BIOIDENTICAL (NATURAL) PROGESTERONE INFORMATION

JEANNIE COLLINS BEAUDIN, Hormone Specialist, Retired Pharmacist

jeannie.beaudin@gmail.com

 

When progesterone cream was removed from the shelves in Canada in the mid-90's due to being reclassified as prescription status, several women who were using it asked if I could supply them.  When I found no products were available in Canada and I could not order it from US as these American products had not been approved for sale by Health Canada, I offered to compound it for them (pharmacists have an exemption to prepare products under a physician's order without having Health Canada approval).  It is noteworthy that progesterone cream is considered safe enough by American regulators to be sold without a prescription in US.  Since I was making the cream and because the clients using it had questions I could not answer, I began reading books and researching journal articles on the subject.  I subsequently attended two seminars on Bio-identical hormones in US and several in Canada.

 

In the course of my research, I have compiled a number of scientific articles that support the use of progesterone in cream form.  I found data to support the absorption of progesterone through the skin (provided certain criteria are met),16 its action on breast tissue,17 its action on bone metabolism18 (although other studies question this action on bone),19 and its choice over synthetic progestins.20 As well, I have accumulated a library of books on the subject.  A bibliography of available texts and copies of these articles are available on request.

 

PROGESTERONE DOSING INFORMATION

Normal cyclic production of progesterone in women is in the range of 20 to 30mg/day.  In pregnancy, production increases to 300 to 400mg/day, so it has a wide safety margin.  The goal of supplemental therapy would be to deliver a dose within this range.  We have patients using 20 to 100mg per day transdermally, with 30 to 60mg being most common.  By comparison, oral progesterone which is highly metabolized by the liver, is dosed as 100 to 300mg daily.  The high levels of progesterone metabolites produced cause the drowsiness that is noted with oral progesterone.  Since progesterone is known to increase receptor sensitivity to estrogens, most women on estrogen-only therapy will need to reduce their estrogen dose when progesterone is added.  Also, because of this increased estrogen receptor sensitivity, some women have adequate relief from hot flashes and other symptoms generally attributed to insufficient or fluctuating estrogen levels by using progesterone alone.  In post-menopausal patients, it is recommended to have a hormone-free period of 4 to 7 days per month to maintain hormone activity.  Pre-menopausal patients would normally supplement only during the luteal phase of the cycle.  Progesterone would only be used throughout the cycle in pre-menopausal patients who were producing unusually high amounts of estrogen, a situation that is becoming more common.21

 

Although some authorities seem to assume 100% transdermal absorption while others estimate as low as 10%, the actual percentage is probably somewhere in between and variable according to the person's individual characteristics as well as the characteristics of the product base.  Absorption has been shown to be consistent within an individual, although it can vary from person to person and correlates with the transdermal absorption of other hormones, such as estradiol.22 We assume absorption of 80 to 90% with a properly milled product that is prepared in a proper base.

 

FACTORS THAT CAN INFLUENCE THE AMOUNT OF PROGESTERONE PASSING THROUGH THE SKIN:

• Site of application (areas of thinner skin may facilitate penetration)

• The vehicle in which the progesterone is applied (mineral oil can decrease absorption as it binds strongly to progesterone)

• Total surface area to which the cream is applied (larger area may result in more consistent blood levels)

• Skin condition (various factors such as presence of skin disease, mechanical or chemical damage to skin, occlusion, temperature)

• Skin age (although not well-proven, it is generally assumed that the skin of the young and the elderly is more permeable than adult tissue)

 

Progesterone and estrogen are well suited to absorption through the skin due to their low molecular weight and lipid solubility, and there are commercial preparations of transdermal patches and gels now being sold.  In the application of progesterone in cream form, the skin acts as a reservoir, maintaining blood levels at a more constant level than many other forms of drug delivery, such as sublingual, oral and rectal.  Progesterone, being lipid soluble, does not travel freely dissolved in aqueous blood but must be bound to red blood cells, proteins or lipid molecules, called chylomicrons.

 

The actual dose for each person will vary, due to individual variations in requirement, absorption and metabolism.  There are many inter-related factors that come into play:

• Increased estrogens, in particular orally administered estrogens, which go directly to the liver on absorption, increase protein production by the liver, including sex hormone binding globulin (SHBG), which binds to estrogen, progesterone and testosterone causing decreased amounts of hormone free to act on tissues.

• Skin contains an enzyme, 5-alpha-reductase that occurs in varying amounts in different individuals, which can metabolize progesterone to different degrees as it is absorbed, depending on the amount present.  "Hairy" individuals tend to have higher levels of this enzyme in their skin.

• Progesterone, being lipid-soluble, is stored in fatty tissues in the body.  When progesterone replacement is started in individuals who have been deficient for a period of time the fatty tissues will initially take up progesterone at a greater rate, leading to decreased progesterone activity when treatment is first started.  Some sources suggest doubling the dose for the first 2 months to compensate for this.

• Discontinuing administration of progesterone for a short period of time each month is recommended by some authorities even after menopause to maintain receptor sensitivity.

• Estrogen is also thought to "prime" progesterone receptors; if lacking in progesterone effect when using this hormone alone, adding a small amount of estrogen may be necessary, although the body can convert progesterone to estrogen.  Menstrual cycles can only occur with a blood estrogen level above 50pg/ml which is also considered to be the lower level goal in estrogen replacement therapy (50-150pg/ml).  If menstrual cycles are occurring the woman would need to have adequate estrogen levels already and estrogen supplementation would be unnecessary.

 

Some clinicians prefer to measure saliva levels of progesterone as these levels represent more accurately the levels of free progesterone, as compared to blood levels that include progesterone bound to protein that is not biologically active.  However, saliva tests are not processed at our local hospital and are therefore not covered by Medicare here in New Brunswick.  The website of the Canadian saliva test lab is www.ramlab.com  and that of the parent company, ZRT Laboratory, which has an extensive reference section is www.salivatest.com .

 

 

HOW TO MONITOR FOR EFFECT

 

• Relief of symptoms such as premenstrual water retention and weight gain, hot flashes, vaginal dryness.

• Bone scan (an increase in bone density would confirm adequate dose, but this would require at least a year of treatment)

• Drowsiness is a symptom of excessive transdermal dosage which is easy to monitor (drowsiness is expected with oral progesterone and may be helpful for insomnia.

• The type and amount of vaginal mucous produced (wet mucous indicates unopposed estrogen).

 

APPENDIX II

General BHRT Information

 

BIOIDENTICAL HORMONE REPLACEMENT

INFORMATION

Jeannie Collins Beaudin, Hormone Specialist, Retired Pharmacist

 

 

When I first heard about bioidentical hormone replacement, particularly administered through the skin in the form of a cream, I thought that it couldn't be valid since there were no commercial versions available in Canada. When I continued to receive questions from clients, along with requests to compound products (mostly transdermal) that were not available, I started researching, reading books and journal articles.  I eventually attended two conferences in US and several in Canada and joined a network of compounding pharmacists, so I would have good answers for these women.  One of the things I learned is that bioidentical hormones, being natural substances, cannot be patented in US.  Therefore, there is little incentive to American pharmaceutical companies to do research and product development. In Canada, a prescription is required for all reproductive hormones, and a lot more documentation is necessary to bring a prescription product to market. That is very likely the main reason for the lack of information and commercial products available to us in Canada.  Progesterone cream, estriol cream and estradiol cream are available without prescription in US, mainly in health food stores. Pharmacists, however, recognizing the monitoring that should occur in women using supplemental hormones, generally require a prescription. This surprising difference may be due to differing federal and state regulations.

 

I am currently a retired pharmacist. My interest is to provide information on effective alternative treatments for women with menopausal complaints. As a compounding pharmacist, I prepared products from USP standardized ingredients for replacement of the three main classes of hormones used in women, the estrogens, progesterone and testosterone.  For estrogen replacement, I made oral as well as transdermal forms, but the transdermal estrogens were the most popular, as stomach upset is avoided and lower doses of the potent forms of estrogen are needed.  It is possible to make hormone replacement as sublingual drops as well, if that is a woman's preference.

 

Most women use one of two formulas we refer to as TriEstrogen (80% estriol, 10% estradiol and 10% estrone) or BiEstrogen (80% estriol and 20% estradiol) that attempt to maintain the natural balance of strong and weak circulating estrogens produced before menopause.  I commonly made a preparation of 1mg total estrogen per ml and I always recommend that women measure the cream with a syringe for an accurate dose.  I find that most women who have not previously taken hormones do well with 0.5 to 1mg daily but those who are switching from Premarin require much higher doses, 2 to 2.5mg daily.  Interestingly, a study sponsored by Wyeth-Ayerst several years ago found good control of menopausal symptoms and fewer side effects with 0.3 to 0.45mg of Premarin than with the most commonly used 0.625mg strength.  I expected that the recommended doses would be lowered but didn't notice any change after the study was released.  It appears that the study was not well publicized. Another reason for lack of uptake of this new information may have been that many studies use Premarin 0.625mg, leaving the effectiveness of the 0.3mg on areas such as bone preservation, for example, untested.

 

Transdermal progesterone was the first bioidentical hormone replacement I began dispensing.  Many postmenopausal women do well with only progesterone, as it increases the number of estrogen receptors and thereby improves the action of endogenous estrogens to sufficient levels. Progesterone can also be metabolized into estrogen, testosterone and other hormones, providing a supply of several hormones.

 

The other situation where I have found progesterone-only therapy to be valuable is with perimenopausal women who are having anovulatory cycles.  Studies by Dr. Jerilynn Prior at UBC and others have found that significant percentages of women in their 40's do not ovulate regularly, with a resultant lack of progesterone being produced during the luteal phase of the cycle.  In significant percentages of these women, the hypothalamus responds by causing the pituitary to release higher levels of FSH resulting in increased production of estrogen (measured as much as 6 to 7 times higher than normal) and in some women increased testosterone is also released by the ovary.  This sets them up for the heavy flow, mood swings, increased PMS, etc., all signs of a domination of estrogen effect throughout the cycle, that conventional medicine tries to control with birth control pills containing a synthetic progestin plus more estrogen.

 

The dominating effect of the progestin in the pill usually fixes the problem with heavy bleeding but does nothing or may worsen other symptoms, such as breast soreness, fluid retention and mood problems.  I found that replacing the progesterone from ovulation until menstruation in an amount sufficient to overcome signs of high estrogen works very well without further increasing their estrogen levels.  I generally would suggest that they monitor for the disappearance of estrogen stimulated "eggwhite" vaginal mucous to gauge the amount needed.

 

I realize that many clinicians use this therapy approach with medroxyprogesterone, but I have seen three studies now in addition to the well-known Women's Health Initiative study, finding significantly increased rates of breast cancer with this drug and often have received complaints of breast tenderness from women using the therapy.

 

Oral progesterone represents an improvement in side-effect profile for many women, but the dose needs to be 8 to 10 times higher than when administered transdermally, due to metabolism during the first pass through the liver.  Side effects such as drowsiness are attributed to the many metabolites produced, not to the progesterone itself.  Women using the transdermal form of progesterone do not experience drowsiness and will often report clearer thinking and better memory function.

 

Transdermal testosterone has been used in women for years, as available oral commercial products are 10 to 20 times the strength needed, being designed for men.  However, instead of a petrolatum base I recommend using a proper transdermal base and loading the cream into syringes to ensure it will be correctly measured.  For women, a maintenance replacement dose is equal to 0.1ml or less of 1% strength – a very tiny amount that will deliver 1mg of testosterone.  I do recommend that they start with 0.2 to 0.4ml daily until they notice some effect, however, to get things started, usually for a maximum of 2 weeks.

 

I have also noticed that excessive production of stress hormones, structurally similar to estrogen, is a significant contributor to menopausal symptoms and sleep disturbances.  As our standard medical system has little to offer for controlling the effects of stress hormones, I have often suggested herbal medications or nutrients that have some evidence of benefit in this area.  Phosphatidyl Serine is believed to lower cortisol production and can be useful for correcting some sleep disturbances; vitamin C and B Complex are involved in the production of cortisol; and several herbs, termed "adaptogens" can reduce the impact of excess cortisol on the body.  It is interesting that the effects of cortisol are similar to the cluster of conditions we refer to as "Metabolic Syndrome".

 

APPENDIX III

Hormone Worksheet

 

HORMONE WORKSHEET                               Payment discussed_____

 

Name__________________     Date____________________

Phone_________________       Birthdate________________

Address________________       Doctor__________________

_____________________Email or fax___________

 

Current medications    ___________________________________

___________________________________

 

Regular periods? ___________

Length____________________

Frequency_________________

Description_________________________________

________________________________________

Other cyclic symptoms _______________________________________

_______________________________________

Pregnancies_______

Miscarriages______________          Main Concerns _____       

Difficulty in getting pregnant? ___          _______________

Surgeries_________________       _______________

 

SYMPTOMS

Hot flashes_______________________________

Night sweats______________________________

Vaginal dryness/mucous_______________________

Urinary symptoms__________________________

Insomnia________________________________

Fluid retention_____________________________

Breast soreness____________________________

Weight gain______________________________

Headaches _______________________________

Heart palpitations___________________________

Fatigue _________________________________

Memory change____________________________

Moods__________________________________

Hair loss/growth____________________________

Bone loss________________________________

Decreased muscle/cramps/aching__________________

Low libido________________________________

Joint pains/arthritis__________________________

Bowel function_____________________________

Body temp/BP_____________________________

Stress__________________________________

 

GOALS AND ASSESSMENT ______________________________________

______________________________________

______________________________________

 

 

Reading List

The following is a reading list that covers several important aspects of hormone function and imbalances in women:

 

Natural Progesterone: The Multiple Roles of a Remarkable Hormone

• Dr. John Lee, author

• Older text, but the definitive text on progesterone, written from Dr. Lee's clinical experiences and research

 

What Your Doctor May Not Tell You About Premenopause

• Dr. John Lee, author

• Good information on irregular/heavy cycles before menopause

 

What Your Doctor May Not Tell You About Breast Cancer

• Dr. John Lee and Dr. David Zava, authors

• Very detailed, not just about breast cancer, but includes extensive information on hormone metabolism

 

The Hormone of Desire

• Dr. Susan Rako, author

• About testosterone use in women

 

Hormone Deception

• D. Lindsey Berkson, author

• About environmental estrogen-like chemicals and their effect on our health

 

 

 

16 . Weichers, J.W., "Barrier Function of the Skin in Relation to Percutaneous Absorption of Drugs". Pharmaceutisch Weekblad Scientific Edition, 11-1989.

17 . Chang, K., et al, "Influences of Percutaneous Administration of Estradiol and Progesterone on Human Breast Eipthelial Cell Cycle in Vivo", Fertility and Sterility, April 1996, Vol.68, No.4, p.785-791.

18 . Prior, J.C., "Progesterone as a bone-trophic hormone". Endocrine Rev.,11(2):386-98, May 1990.

19 . Leonetti HB, et al, "Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss", Obstet Gynecol, Aug 1999; 94(2):225-8.

20 . Schairer, C. , "Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk". JAMA, Jan 26,2000, Vol.283,No.4.

21 . Prior, J.C., "Perimenopause – The ovary's frustrating grand finale", A Friend Indeed, Vol xiv, No.7, Dec97/Jan98.

22 . Burry KA, et al, "Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen", Am J Pbstet Gynedol, June 1999; 180(6 Pt 1):1504-11.