NATURAL BIO-IDENTICAL PROGESTERONE
Natural progesterone is produced by the ovaries, the adrenal glands and during pregnancy in women, also by the testes and adrenal glands in men. In a woman, progesterone helps to balance oestrogen. Progesterone is known as the " happy hormone"...... it is what gives pregnant women that lovely glow and is responsible for their relaxed state of being that we are all only too familiar with.
With regards to a maturing woman, oestrogen dominance may result if the level of progesterone relative to oestrogen is too low. This can manifest with symptoms such as breast tenderness, insomnia and heavy periods. Excess oestrogen with a relative deficiency of progesterone can cause the lining of the uterus, the endometrium to become thicker than normal. This can lead to endometrial hyperplasia and if left untreated can lead to endometrial cancer. It is thus extremely important for a woman with a uterus who is taking oestrogen hormone replacement therapy, to also take progesterone to prevent the excessive thickening of the endometrium which can lead to cancer of the endometrium.
Ron Rothenberg MD, has commented that with regards to women who have had a hysterectomy, a controversy exists. Traditional Medicine teaches that in a woman who has had a hysterectomy, progesterone is unnecessary if she is taking oestrogen hormone replacement since the main concern of unopposed oestrogen is endometrial hyperplasia and the development of uterine cancer and without a uterus, this risk does not exist. However, progesterone receptors are widely found throughout the body including in every brain cell, breast tissue, the heart and skin. Many prescribers of BHRT will thus prescribe bio-identical progesterone for women who have undergone a hysterectomy including myself. Bio- identical progesterone replacement therapy has many health benefits. Thus, it is most important to keep progesterone levels within a youthful physiological range. It must be remembered that oestrogen and progesterone have a complimentary effect and that Progestins are not progesterone.
Progesterone Deficiency symptoms:
Progesterone is often the first hormone to become deficient during the peri- menopause and menopause. Levels of progesterone often decline faster than oestrogen during this period. It is for this reason that often progesterone treatment is commenced initially for the treatment during this period with the addition of oestrogen later.
Symptoms due to lack of progesterone include:
Benefits of progesterone:
A natural diuretic
A natural antidepressant
Protects against endometrial cancer
Protects against fibrocystic disease of the breasts.
POSSIBLE SIDE EFFECTS OF PROGESTERONE
Bio-identical Progesterone can be used in the form of a trans- dermal cream or a lozenge both of which are not subjected to the first pass liver effects. If a patient is complaining of poor sleep which is a very common symptom in peri-menopausal or menopausal women, the micronized form of oral Progesterone in capsule form can be very effective to improve sleep. This oral form of Progesterone often prescribed as Utrogestan, has more sedative effects due to the conversion to 5-allo-Pregnenolone which takes place in the liver. There is less of this break down product in trans dermal products. Unlike oral Oestrogens, oral Progesterone does not initiate an acute phase response within the liver and so there is no increase in inflammation or cardiac risks with this formulation. Dr. Berry's practice is not to prescribe trans-dermal Progesterone. Trans-dermal Progesterone does not give adequate protection to the endometrium ( lining of the womb) which is necessary if a woman is using Bio- identical Oestrogens. Inadequete protection of the uterus in a woman using an Oestrogen, can lead to endometrial hyperplasia and carcinoma.
Progesterone may cause a patient to experience morning sedation (unusual), bloating and typical pre-menstrual symptoms such as mood changes. Progesterone intolerance can also can occur in any woman but Dr. Berry has noted this is especially so in women of a low BMI or who are anorexic or have a history of anorexia. If this is the case, the dose of progesterone can be possibly be reduced ( always ensuring adequete endometrial protection) or in the case of Utrogestan, this can be used rectally. Progesterone can have fluid retaining side effects which is responsible for bloating and breast tenderness, also weight changes although these are not common. Progesterone can also cause nausea, headache and dizziness, again these are unusual. There should be no side effects however if the dose of Progesterone is within the physiological range. Dr. Berry always uses the lowest dose of bio-identical hormones that is effective and safe, thus minimizing any possible side effects.
Of note, Progesterone is contra indicated if a woman has a history of liver tumours or has a history of genital or breast cancer,severe arterial disease, undiagnosed vaginal bleeding and acute porphyria. Progesterone should also not be used if there is a history during pregnancy of idiopathic jaundice, severe pruritis or pemphigoid gestationis.
Also of note, caution needs to be exercised with regards to the use of Progesterone in conditions that may worsen with fluid retention such as epilepsy, hypertension, migraine, asthma and cardiac dysfunction. Caution also needs to be exercised with regards to women who have a history of depression. Progesterone may decrease glucose intolerance and so patients who suffer from Diabetes require more close monitoring of blood glucose levels and of their Diabetic control.
Dehydroepiandrosterone ( DHEA) is a hormone that rapidly declines with age. The adrenal glands manufacture DHEA from cholesterol. A small amount is also manufactured in the ovaries. DHEA is the precursor for many other crucial adrenal hormones which are essential for health. Levels of DHEA are at their highest between 20-25 years of age. After this age, levels decline by approximately 2% per year. At age 40, we make around 50% of the DHEA we make at 25 years of age.
DHEA is a very important hormone for health. Studies show that the lower one's DHEA level is, the more likely it is that one suffers from the chronic degenerative diseases of ageing such as cancer, atherosclerosis and osteoporosis. These chronic diseases of ageing seriously affect ones's quality of life not to mention the fact that some of these diseases can cause a premature death. In the case of cancer, the risk of some cancers increases as levels of DHEA fall.
Dr. Berry routinely measures a DHEA level when performing a baseline hormone profile for new clients. The levels are often low in maturing individuals. A small dose of bio- identical DHEA can often make a significant difference to the well being of a clients. It must be remembered that DHEA is contra-indicated if one has a history of breast cancer or prostate cancer.
DHEA boosts ones's feeling of well being and also is also good for client's with a low libido. In clients with a low Testosterone level and a low libido, a small dose of DHEA can significantly improve libido. DHEA can be used for this purpose if the Testosterone level is low or borderline low. DHEA is also very useful if one has a history of osteoporosis or osteopenia. The hormone increases the activity of bone building cells and inhibits the activity of bone destroying cells. DHEA is also good to improve memory and to enhance the immune system which often can be compromised as one ages.
Before Dr. Berry prescribes DHEA she needs to be aware of any medications that the client may be taking so as to avoid any potential interactions.
THE THYROID HORMONES
Dr. Berry routinely measures a baseline TSH ( Thyroid Stimulating Hormone) when performing a baseline hormone profile for a new client. The TSH gives an indication as to whether the thyroid gland is under active (Hypothyroidism) or over active (Hyperthyroidism). If the TSH level is abnormal, other thyroid hormones T3 and T4 will be measured to provide more information about this very important gland which controls ones's metabolism. An underactive Thyroid can occur insidiously over time and it's symptoms can be almost imperceptible.
Symptoms of an under active thyroid include constipation, weight gain, fatigue, depressive feelings, dry hair and skin, " brain fog" with poor concentration and poor memory. These symptoms can be remedied by replacement with the appropriate dose of Levothyroxine with follow up monitoring and blood testing. The cause is often an auto immune Hashimoto's Thyroiditis.
Symptoms of an over active thyroid tend to manifest earlier with palpitations, weight loss, diarrhoea, tremor of hands, nervousness, anxiety and prominent eyes which can appear to have a bulging appearance. The cause may be a thyroid nodule which may need treatment in its own right. Drug treatment if appropriate is with Carbimazole with regular follow up monitoring and blood testing.
As DHEA levels in women gradually reduce with age, so do Testosterone levels (Schneider 2003). Loss of Testosterone affects libido, bone and muscle mass, vasomotor symptoms, cardiovascular health, mood and well being ( Simon 2001; Watt 2003). Testosterone, in women is produced in the ovaries and in the adrenal glands via DHEA. Ron Rothenberg MD states that Bio- identical Testosterone replacement therapy can also decrease inflammation, improve energy levels, in erase bone density, decrease blood pressure, decrease cardiovascular disease, lower LDL cholesterol levels, improve brain function and decrease body fat.
Symptoms of Testosterone excess in women include oily skin, acne, scalp hair loss, unwanted body hair, "too much" libido, aggressive behaviour and salt and sugar cravings. Elevated Testosterone levels in women can be caused by over treatment with Testosterone or PCOS ( Poly Cystic Ovarian Syndrome).
DHEA may raise Testosterone levels in women but not in men. DHEA converts into Testosterone, therefore it is possible to raise Testosterone levels with DHEA (Cameron 2004; Schneider 2003). Testosterone can be prescribed in a trans-dermal cream.
Dr. Berry includes a Testosterone level ( free and bound) in her basic hormone profile for all new patients. This is repeated if necessary as part of hormonal monitoring.
Pregnenolone is derived from cholesterol, as are all the other steroidal hormones. As we age our Pregnenolone levels decline by as much as 60% by the time we have reached 75 years of age. Pregnenolone is known as the "grand-mother" hormone in the body because it is the precursor to Progesterone and to DHEA, which in turn is a precursor to the sex hormones Testosterone and Oestrogen.
Large concentrations of Pregnenolone are found in the brain and supplementation has been shown to improve many of our mental functions, including mood and cognition. It has been shown to decrease fatigue, enhance memory and improve one's ability to cope with stress.
No significant adverse effects have been observed with Pregnenolone supplementation. However, blood testing and monitoring of symptoms is important. If DHEA-s levels are sub-optimal, Pregnenolone levels will probably also be sub-optimal. When clinically indicated Pregnenolone can be prescribed in the dose of 100-200 mg daily. Ageing women should maintain a Pregnenolone blood level of 130-180 ng/ l for optimal performance.
Oestrogen is not a single hormone but a group of hormones. There are 3 types of Oestrogen: Oestrone (E1), Oestradiol (E2) and Oestriol (E3). Oestradiol is the most potent Oestrogen in the body and is necessary for the beneficial effects on heart and brain. Oestriol is a weak oestrogen and has been shown in some previous studies by US physicians to have anti-cancer effects on breast tissue. Evidence now seems to be lacking on this issue. Present evidence indicates that Estriol does not protect breast tissue. During the Menopause E1 levels rise dramatically to about 80% and the E2 and E3 levels drop leading to a deficiency syndrome. Hormone levels can begin to decline in the peri-menopausal years which can be as early as 35 yrs of age. According to Ron Rothenberg MD, a pioneer of Preventative and Regenerative Medicine, these hormone deficiencies can have multiple deleterious effects on the cardiovascular, neuro-cognitive and musculo-skeletal systems
Symptoms of Oestrogen deficiency may include: anxiety, depression, night sweats, insomnia, fatigue, hot flushes, tearfulness, mood swings, vaginal dryness, cystitis, reduced libido, urinary frequency and incontinence, increased wrinkles, shortness of breath, palpitations, decreased memory and attention span, increased body weight, increased blood pressure and cholesterol levels, osteoporosis.
Dr. Berry used to prescribe Bi-Est trans-dermal cream. As its name implies, it is a combination of 2 oestrogens, Oestradiol (E2) and Oestriol (E3). It is usually prescribed in the ratio of 20:80 i.e. 20% Oestradiol and 80% Oestriol. Since the evidence is lacking regarding Oestriol, Dr. Berry no longer prescribes this formulation. Instead, Dr. Berry prescribes Oestradiol in varying strengths depending on symptoms and blood results. It can be applied in the morning if it is once daily or can be prescribed twice daily, morning and evening depending on symptoms and blood results. It should be applied over a reasonably sized area and thinly to improve absorption, either to the inner aspect of the thigh or to the inner aspect of the forearm but must never be applied close to the breasts or genital area. The skin must be clean and free of moisturizer or perfume. Clothing should not cover the area for approximately 15 minutes until the cream is dry. Oestradiol cream can be applied continuously i.e. daily with no breaks or cyclically, that means with breaks. Dr. Berry more often uses the latter protocol in peri-menopausal patients. In women who have been using conventional HRT (CHRT) and wish to change over to BHRT, a gradual reduction in the CHRT may be necessary during the transition period to avoid troublesome hot flushes. This is because CHRT has a long half life i.e. it remains in a woman's system for a longer period of time compared to BHRT and so takes a longer time to flush out of the system. During this time, it may be necessary to reduce the CHRT from daily to alternate day dosing, then to twice weekly dosing etc whilst at the same time gradually increasing the Oestradiol cream, until a balance is achieved. Doses of Oestradiol cream are then titrated up or down depending on symptoms and the results of blood testing.
Dr. Berry often prescribes intrabuccal lozenges for patients who have a preference for lozenges or for some patients who are non-absorbers of trans-dermal preparations for whatever reason. There is no first pass effect with regards to the liver, that is that these products once absorbed via the blood vessels of the mouth, do not pass through the liver. The lozenges need to be placed between the teeth and upper lip or alternatively under the tongue. They dissolve slowly in the mouth and must not be sucked or swallowed. A lozenge will take approximately 15 minutes to be absorbed. During this time there must be no food or fluid in the mouth. A number of different hormones may be included in one type of lozenge. If Progesterone is included, this can cause a bitter taste. In this case flavouring is necessary. Stevia is used which is a natural sugar substitute. It contains zero calories. One advantage of the lozenge form is that higher doses of hormones can be used and they may be better for patients who have a sensitive skin. All lozenge preparations can be quartered. A patient will typically be prescribed a one quarter lozenge morning only or morning and evening.
Metabolism of Oestrogen: Oestrogen can be metabolized (broken down by the body) into a “good” metabolite ((break down product) or a “bad” metabolite. It is preferable that Oestrogen is metabolized via a “good” metabolic pathway thus giving protection against breast cancer. Metabolism via a “bad” metabolic pathway can increase the risk of breast cancer.
2-Hydroxy-oestrone is considered a “good” Oestrogen. It has weak oestrogenic activity and is considered to protect against breast cancer. It’s metabolism is supported by cruciferous vegetables containing indole-3-carbinol, such as broccoli, cauliflower and cabbage. Other supporters of this pathway include soy Isoflavones, flaxseed lignans, omega 3 fatty acids, rosemary, tumeric, exercise & wt loss. Cruciferous vegetables in particular can help to maintain a favourable ratio of 2-hydroxy to 16-hydroxy metabolites. It is to be noted that excess cortisol secretion due to mental stress, can result in the reduced production of the favourable 2-hydroxy metabolite, thus elevating cancer risk according to Ron Rothenberg MD.
16-Hydroxy-oestrone is considered a “bad” oestrogen. This can be associated with an increased risk of breast cancer. This “bad” metabolic pathway is supported by obesity, low thyroid function (hypothyroidism), pesticide toxicity, omega 5 fatty acid excess and inflammation. Low 2:16 hydroxyoestrone ratios are associated with breast cancer.
Dr. Berry will periodically check how a client is metabolizing Oestrogen during treatment by asking the patient to provide a urine sample. A urine analysis will inform her whether a client’s oestrogen is being metabolized via a “good” or “bad” pathway. If the result indicates a “bad” metabolic pathway has been adopted, then increased nutraceutical support for the good metabolic pathway is advised along with weight loss and increased exercise if applicable with further monitoring of the urine.
Side effects of treatment of Oestrogen Therapy: Excess levels of Oestradiol may be associated with side effects including an increased risk of breast cancer and endometrial (lining of the womb) cancer. This is why monitoring and blood testing is so important. Other adverse effects include nausea, increased vaginal discharge, increase in size of fibroids, tender or enlarged breasts, skin irritation (redness, swelling) at the site of application of a trans-dermal preparation. Of note is that oral oestrogens as in conventional HRT increase inflammation and so should not be given orally. Oral Oestrogens since they pass through the liver (first pass effect), increase acute phase proteins including CRP (C Reactive Protein) and fibrinogen and thereby increase the risk of thrombosis and blood clots according to Ron Rothenberg MD. Blood clots may thus form in the calf veins (DVT) or in the lungs (pulmonary embolus, PE) in women taking conventional HRT. Trans-dermal oestrogens and bio-identical (natural)progesterone do not increase the risk of DVT or PEs (Archer). This includes bio-identical lozenges that Dr. Berry often prescribes. If a patient experiences a severe headache or chest pain whilst taking any form of HRT, the treatment must be stopped and the patient's doctor consulted immediately. Of note, recent NICE guidance states that normally 22 women in every 1,000 will get breast cancer over 7 years. NICE states that if they all took HRT there would be 5 extra cases per 1,000 women over 7 years. Dr. Berry monitors each patient closely for possible side effects. With each client she discusses a breast cancer prevention strategy, gives written information and instructs each client to perform a breast self exam each month after showing each client how to perform this correctly. With regards to the uterus (womb), Dr. Berry likes all new clients to have a baseline ultrasound of uterus to look at the thickness of the lining of the uterus and periodically after this to detect endometrial hyperplasia and carcinoma.
INFORMATION ABOUT INDIVIDUAL HORMONES OESTROGEN
Oestrogen is the hormone that makes us female. Oestrogen receptors are found in numerous tissues through-out the female body including the breast, brain, heart, arteries, bladder, vagina and skin. Oestrogen is synthesized primarily in the ovaries. It is responsible for regulating the menstrual cycle, breast development and for fertility, also for the passage through the Menopause. Oestrogen has many benefits throughout the body, including maintenance of memory, bone density, collagen levels in the skin, and of arterial elasticity. It improves mood and concentration and also lowers the risk of bowel cancer and heart disease.
and contribute to an inflammatory state. When hormones are replaced and balanced, inflammation is decreased. Replacing deficient hormones in the body with bio-identical hormones can decrease cholesterol levels, improve memory, reduce the onset of osteoporosis and heart disease. Symptoms related to the Menopause such as hot flushes, mood swings, anxiety, night sweats, urinary symptoms and fatigue are the main reasons for treatment but the major benefits are found in the reduction of cardiovascular disease, Osteoporosis and neurological decline. Of particular interest is a recent trial which shows that HRT reduces cardiovascular endpoints in a ten year trial ( Schierbeck, Rejnmark, Tofteng et al: Effect of HRT on cardiovascular events in recently postmenopausal women: randomized trial. BMJ 2012; 345 & Rossouw, Prentice, Manson et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007; 297). Dr. Berry's particular interest is that of Atherosclerosis and the prevention of cardiovascular disease in women. Cardiovascular disease can lead to heart attacks and strokes. Oestradiol (E2 ) is the strongest Oestrogen in the body. It is very effective for the relief of hot flushes and night sweats, also for the relief of genito-urinary symptoms such as urinary frequency and frequent urinary tract infections. It also helps mood swings and psychological symptoms. It is anti-atherosclerotic, increases HDL (“good” cholesterol) and lowers total cholesterol. Thus, it helps reduce heart disease as it is cardio-protective. It is the Oestrogen that also protects the brain. Oestriol (E3) is the weakest of the 3 major Oestrogens and is the Oestrogen that is made in large quantities in pregnancy. A 2006 study by Schmitt in Gynecologic Endocrinology points out that low levels of Oestriol (E3) are associated with increased breast cancer risk. This study also points out that Oestriol is also protective of heart and brain function. Oestriol is also beneficial to the vagina, cervix and vulva. Topical Oestradiol in the form of a pessary can be used in cases of Atrophic Vaginitis which can result in dryness, itching and burning. This is the safest and most efficient form of Oestrogen to use. Absorption into the systemic circulation is minimal but may be a consideration for women who have a history of breast cancer.