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Transdermal or Oral Progesterone


What does the evidence say?

Often questions are asked which form of progesterone better, oral or transdermal. Why does one recommend progesterone?  What are the basis and effects of the form of progesterone used?

Progesterone is a naturally occurring steroid hormone. Its half-life is only 5 minutes and it has a very poor bioavailability orally.

Progesterone causes the secretory transformation of the endometrium from the estrogen-induced proliferative phase during the second half of the menstrual cycle. Progesterone also exerts its effect on the breasts and the CNS.


Progesterone is primarily being used to manage following conditions:

  1. To regulate the menstrual
  2. Treat dysfunctional uterine bleeding.
  3. Prevention endometrial cancer or hyperplasia in unopposed estrogen stimulation. Progesterone reduces estrogen receptors in endometrial glands. It also regulates mitosis in fully differentiated endometrial cells.
  4. It is also used as a form of contraception.
  5. It has been used to treat dysmenorrhea and premenstrual syndrome.
  6. It is also has been used to prevent, control and possibly reverse ovarian cysts and fibroadenomas of the breast. In addition, further enlargement of fibroids and formation of new fibroids may be controlled but reducing the size of existing fibroids needs long term use. Furthermore, menorrhagia secondary to fibroids can be controlled thus avoiding surgery in most cases.

Synthetic analogues of progesterone called “progestins” are associated with much side effects like-fluid retention, reduction on HDL, headache, mood disturbances and androgenic effects.


But natural progestogen that is primarily obtained from plant source has not been shown to affect the mood, reduction HDL or adversely affect pregnancy outcome.

Since natural progesterone has been associated with poor bioavailability, a micronized form has been developed to minimize this issue. With micronizing, the half-life of progesterone is increased and its destruction in the gastro intestinal tract reduced.


Various clinical trials have established that the sequential oral use of 200 mg progesterone daily offers reliable protection against undesirable effects of oestrogen on the endometrium, i.e. it prevents endometrial hyperplasia.





The USA PEPI study is a landmark trial. It showed the evidence of the endometrial safety of hormone replacement therapy (HRT). 875women were treated for three years with various HRT regimes, including one arm with oral administration of 200 mg micronized progesterone daily on 12 days of every month as an addition to a standard dose of 0.625 mg conjugated equine oestrogens (CEE) daily. The incidence of endometrial hyperplasia was no difference as that found under placebo (1–4% of the women), whereas the 3-year use of oestrogen alone led to such hyperplasia in 62% of the women.


The KEEPS trial included 727 women who were newly menopausal. The trial tested 2 different types of oestrogen compared with placebo: a low-dose oral conjugated oestrogen at a dose of 0.45 mg/day, and a transdermal estradiol patch at a dose of 50 µg/day. Both [forms of oestrogen were taken] with cyclic micronized progesterone for 12 days per month.


There was a substantial reduction in menopausal symptoms (hot flashes, night sweats) and also some improvement in bone mineral density [were seen in the active treatment groups]. Systolic blood pressure was not increased and there was the neutral effect on cognitive function.


Natural progesterone and synthetic progestins do have different adverse effects profile. Fournier, et al studied the different HRTs and breast cancer risk. His study involved 80,377 postmenopausal women up to 12 years of follow-up. His result showed that breast cancer risk is associated with the use of oestrogen alone, and in those who use oestrogen with other synthetic progestins. However, oestrogen in combination with micronized progesterone or dydrogesterone is not associated with an increased risk of breast cancer.


The transformation from the reproductive to the post-reproductive phase in a woman’s life lasts a few years. It is characterised by cycle disturbances ranging from dysfunctional bleeding to secondary amenorrhoea, which can be treated with oral micronized progesterone evidently. How about transdermal form?


The transdermal use of progesterone.


When progesterone is used transdermally, there is a reservation with regards to the inadequate therapeutic serum level. These raised doubts about corresponding systemic effects. In the majority of the studies, progesterone creams used were unable to achieve peak serum level of more than 1ng/ml. The normal reference range quoted during luteal phase is usually 5 to 20 ng/mL. In some studies, however; the salivary levels of progesterone did increase significantly especially in postmenopausal women and fingertip capillary blood but without a concurrent dramatic increase in the serum level.


Most of the progesterone used in menopausal women is to protect overstimulation of the endometrium by the concurrent use of oestrogen. But the transdermal use of progesterone may not be able to provide sufficient blood and tissues level to protect the endometrium. Arvind Vashisht and associates did a study on the effects on the endometrium for women using a novel combination of transdermal oestradiol and natural progesterone cream as part of an HRT. Women at least 2 years of post menopausal were recruited and they applied 40 mg natural transdermal progesterone cream and 1mg transdermal oestradiol daily. They have concluded that the dose of natural progesterone cream in their study was insufficient to fully attenuate the mitogenic effect of oestrogen on the endometrium.


Australian researchers led by Wren also showed no progestogenic effect of the sequential addition of transdermal progesterone 16–64 mg daily given for 14days per 28-day cycle to continuous use of 100 microgram estradiol daily; about 90% of the women showed a proliferating endometrium after three cycles.


So far there are conflicting results with regards to the effect of transdermal progesterone alone in reducing vasomotor symptoms.


Bernster and co-workers sought to evaluate the effect of progesterone cream on the climacteric symptoms in post-menopausal women. 223 healthy postmenopausal women, aged between 40 and 60 years and complaining of severe menopausal symptoms was recruited. They were randomly allocated to progesterone cream 60, 40, 20, 5 mg or placebo, to be applied daily continuously for six months. There were no statistically significant differences between any of the treatment groups and placebo for any of the components of the Greene Climacteric Score. They concluded that Progesterone cream was no more effective than placebo for relief of menopausal symptoms.


Whelan AM and co-workers did a systematic review of the effect of transdermal progesterone on climacteric symptoms. 3 RCTs were identified.  2 RCTs failed to see the beneficial effect. Only 1 RCT which used specific compounded progesterone for the trial showed a beneficial effect. The author concluded that available evidence from RCTs does not support the efficacy of bio identical progesterone cream for the management of menopause-related vasomotor symptoms.


Wren BD and co-workers did an RCT comparing the effect of a transdermal cream containing progesterone (32 mg daily) with a placebo cream over a period of 12 weeks. There was no detectable change in vasomotor symptoms, mood characteristics, or sexual feelings, nor was there any change in blood lipid levels or in bone metabolic markers, despite a slight elevation of blood progesterone levels.


Studies conducted to date with progesterone cream have no consistent effects on bone metabolism, lipids, inflammatory and clotting parameters or on the progression of atherosclerosis. Bernster B and co-workers ivestigated 131 post-menopausal women between 50 and 75 years, each with at least one atherosclerotic plaque detected by ultrasound was divided into groups and instructed to use 40 (2 × 20) mg progesterone as cream or placebo for 3 years. No major differences between progesterone cream and placebo were noted. The authors concluded that in the dosage used, the progesterone cream has no influence on the course of atherosclerosis or the preservation of bone.

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Garden of Eden

Major religions believe in the existence of a perfect place where life can be sustained in the best of everything, including health. The place is called with different names in different religions. In this article, let us refer this place as Garden of Eden.

It is said that in this Garden of Eden, life is truly in a perfect harmony with nature. Apparently, nobody is getting sick or getting older in this Garden. The Garden boasts beautiful surroundings where water from rivers are rejuvenating and fruits of the trees are the staple diet for the inhabitants. In one version, apparently human and animals live side by side in the garden and no animals or human eating another animal. In this utopian garden, everyone and every animal is a vegetarian!

Whoever created this concept of the Garden of Eden as a perfect place to live a healthy life must be a great physician specializing in anti-aging medicine (preventive medicine). In today’s world, we are afflicted with many sicknesses precisely because we are not living in the Garden of Eden.

To stay healthy, therefore, we should behave as if we are still living in this Garden. Everything we do, what we eat, the air we breathe, the water we drink, how we eat and drink should be similar or closely resemble what we have in the Garden. In short, we should create our own Garden of Eden.

Today, when you woke up, you probably had coffee with milk for breakfast. I doubt they have those in the Garden. Other than coffee, you may have eaten something with rice and noodles. Garden of Eden does not have those either. After breakfast, you may be resting watching your favourite program on television while drinking some more sugary drinks. Again, I don’t think the Garden of Eden has television or sugar. On weekend, you may be visiting the malls with your family and you get there by driving your car. Again, it is unlikely you can do this in the Garden of Eden. I am sure, human do lots of walking and running (and sleeping) in the Garden of Eden.

Now, you may be thinking that this Garden of Eden is not a nice place to live after all.

If it is still not obvious, let me spell it out for you. The Garden of Eden is a perfect place to live a healthy life because of its nature and originality. Everything in the garden is free from human manipulation and contamination. We are sick because most of the food we eat are not natural. We are ill because most of the things we do are not natural. We are diseased not because we have been cast away from the Garden of Eden but because we have forgotten to live in the way of the Garden.

Next time when you are eating or doing something, remind yourself whether this is resembling or even possible in the Garden of Eden.

Article contributed by: Dr Rizin H Kusop. MBBS, MSc (Anti-Aging, Regenerative and Aesthetic Med), Dip. Family Med. (

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It is known as a broad-spectrum anti-aging hormone.  DHEA administration has been shown to alleviate many age-related conditions and may slow aging process itself.  Studies have shown DHEA mounts a triple attack against three of the most prominent risk factors of cardiovascular disease

  1. Atherosclerosis
  2. Endothelial dysfuration
  3. Metabolic syndrome

By the time you reach age 70, your DHEA levels likely to be 75 – 80 % lower than when you were at your peak.  One study found that men with lowest DHEA levels were 67% more likely to die from a heart attack and 54% more likely to die from any cause.

DHEA (dehydroepiandrosterone) is a hormone produced mostly in adrenal glands.  It is most abundant of all circulating steroid hormones.

A growing body of evidence indicates that maintaining youthful DHEA levels in your blood is a good way to fend off some of the most immediate threats to your longevity mainly cardiovascular disease.

Three of the main risk factors that promote cardiovascular disease are atherosclerosis (hardening of the arteries), endothelial dysfuration (poor function of the lining layer of blood vessels), metabolic syndrome (combination of central obesity, poor blood sugar control, disturbed lipids and high blood pressure).

Numerous studies have established close connection between low DHEA-S levels and arterial narrowing and other characteristics of enteral walls.  Another study showed low DHEA-S levels correlated with thickness of carotid artery (main brain artery) in men and with decreased mean blood flow in carotid artery in women.

Low DHEA-S levels are also associated with risk of atrial fibrillation.  The disordered, fluttering contractions of the upper chambers that can result from atherosclerosis.  In arterial lining cells in culture, DHEA administration inhibited some of the first steps in the development of atherosclerosis.

They are done by suppressing markers of oxidation, reducing inflammatory signals, inhibiting the adhesion molecules that make platelets and other cells stick to artery walls to form obstructive plaques.

Endothelial Dysfunction

Another major risk factor for cardiovascular disease is endothelial dysfunction.  Endothelium plays important role in heart health because it responds to changes in blood flow and pressure.

The endothelium uses nitric oxide and other molecules to signal smooth muscle in artery walls to constrict or relax in response to need.

Damage to endothelial layer occurs as oxidised fats begin to build up.  Endothelial dysfunction results in poorly responsive arterial walls, which often overgrow and thicken, further limiting their suppleness.

Inflammatory changers within the vessel wall rapidly contribute to further dysfunction, loss of responsiveness and eventually to plaque formation.  Studies are showing DHEA can inhibit many of threats to endothelial that can lead to cardiovascular disease.

Treating endothelial cells in culture with DHEA reduces very and earliest inflammatory changes by decreasing expression of proteins that triggers inflammation.

Metabolic Syndrome

Metabolic syndrome is a major treat to cardiovascular heath, an accelerator of aging and cause of premature death.

The risk of dying a cardiovascular death increased by up to 200% in people with metabolic syndrome.  As DHEA declines, rate of metabolic syndrome rises, since DHEA regulates most of the processes that influence metabolic health.

Laboratory studies have shown DHEA administration reduces abdominal fat and insulin resistance.

Additionally specifically in obese women (both pre and post-menopausal) 100mg per day of DHEA supplementation decreased plasma saturated fatty acids and increased level of proactive fatty acids such as omega 3 and omega 6.

Bone Health

DHEA appears to contribute to stronger bones in both men and women.  In older women with a daily dose of DHEA also improves muscle strength and physical function.  These changes help to reduce fracture by simply reducing risk of serious fall in the first place.


DHEA is a potent regulator of many processes that if uncorrected raise your risk of heart attack, stroke or other degenerative catastrophes.  Studies shows people with cardiovascular disease have significantly lower levels of circulating DHEA.

DHEA is Predictor Hormone which means to say that LOW LEVELS PRECEDE  DISORDERS by 10-15 years . Hence regular monitoring even among healthy adults is important . DHEA Defi is closely associated with Autoimmune Disorders.”

People with low DHEA levels die younger than those with more youthful levels.  Regular supplementation with modest doses (15 – 50 mg per day) of DHEA significantly reduces main risk factors of cardiovascular disease.

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The world is gripped with the fear of Cancer. Currently it is estimated that 1 in 3 person runs the risk of getting this most feared disease. It is estimated  that 1,200 new cases are dismissed every day in the USA. This translates into about 21,000  new cases per day around the world. This is an alarming figure. The rate has been ever increasing in spite of the all the advancements both in the diagnosis and treatments. The success in conquering the established Cancer has been very dismal. Where have we gone wrong? Why aren’t we swallowing the bitter pill of truth that the current management is not effective and we need to re-evaluate the treatment strategies? Why aren’t we asking the pertinent question as to why are we not thinking outside the conventional box? For any treatment to be successful, first the underlying cause(s) must be identified and controlled. Then the treatment should be holistic addressing the whole body and the  needs  of the body in terms of vitamins, minerals, essential fatty acids, amino acids etc. Conventional treatment sadly misses out these essential healing essences.

A study done by the Canary Cancer Institute showed that with early diagnosis the successful outcome can be seen in 9 out of 10 cancer patients whereas with late diagnosis it turns down to 1 in 10. The outcome can only be improved if we address 2 very critical issues.


There are many reasons for Cancer to grow and metastasize in our body. Some of the important causes are diet with high sugar (Glucose & Fructose), an over acidic body, environmental toxins (pesticides, chemicals, GMO& GM FOODS), Stress etc. Among these the most important and sensible target to focus will be to cut the food supply chain for the cancer cells. It was clearly explained as early as 1931 by one of the best brains in biochemistry of the 20 th century, Otto Warburg. He demonstrated that Cancer cells live on Glucose. However, Cancer cells use Glucose differently from healthy cells. In healthy cells, Glucose is burned for energy in the Mitochondria using Oxygen (Oxidative Phosphorylation). This is a very efficient way of energy generation (32 calories per gram of Glucose). Unfortunately, there is always “Smoke” (Free Radicals) from this metabolism of Glucose.  Hence the more Glucose is burned for energy (OVERCONSUMPTION OF CARBS & GLUCOSE) the more smoke you get and this directly damages the Mitochondria, the very energy units of the cell. This results in Mitochondrial DNA damage, Dysfunction, Decay and a Reduction in the number of Mitochondria. This primary damage that occurred in the Mitochondrial DNA results in Mutations in the Nuclear DNA, SETTING THE STAGE FOR CANCEROUS TRANSFORMATION OF A HEALTHY CELL. Hence, DNA mutations are a secondary effect of Mitochondrial damage by Free Radicals and this is by and large by Glucose consumption especially in excess. Cancer cells adapt to these  changes in energy crisis within the cells by hijacking the energy production for the Mitochondria to the Cytoplasm and without using Oxygen. This then becomes a fermentation process resulting in the production of Lactic Acid inside the cells. After all, we still possess our rudimentary evolutionary Cytoplasmic Metabolism of Glucose via Fermentation where there is either no need or very little need for glucose.

Every way you look at,  the effective way to prevent & treat cancer will be to STOP FEEDING CANCER CELLS –  GLUCOSE. This is where the Ketogenic Diet paves the way to win the battle WHICH WE ARE NOT ACHIEVING WITH THE CURRENT & ADVANCED CONVENTIONAL TREATMENTS! A Ketogenic  consists of No Glucose (Simple Sugars such as Table sugar, Rice and rice based foods, all Gluten and Non Gluten Grains, Honey, Fruits), 70-80% Good Fats (Virgin Coconut Oil, Eggs, Organic Butter, Avocados, Nuts), some Proteins 10-20% and the smallest amount of carbs 12%  as Complex Carbs from Green Leafy Vegetables, Broccoli, Cauliflower, Cucumber etc. It is good to avoid vegetables rich in sugar such as Carrots, Beetroot, Potatoes.


The cure rate of Cancer is 9 out of 10 with early diagnosis, but this figure drops to 1 out of 10 with a late diagnosis. The current way of assessing the risks of Cancer by Tumour Markers, PET Scan, CT Scan, MRI, Scopes etc. are not without value. However, the diagnosis is often late, a stage 3 or 4 Cancer.  CIRCULATING TUMOR CELLS (CTC) as a way of early diagnosis have been available for some time now and is a hot topic in most of the Oncology conferences. While the earliest diagnosis with the current conventional diagnosis is a tumour of 0.7 cm or bigger, CTC  can detect as small as 0.1 cm tumours that have shed their cells in the peripheral circulation. These circulating cells are also the CANCER STEM CELLS which are the cells that can metastasize and grow into secondary tumours. Sadly, most of the deaths from Cancer are due the these secondary tumours. CTCs can also be used as a warning sign of the  potential for tumour growth. It also offers the biggest benefit HELPING TO CHOOSE THE TYPE OF CHEMOTHERAPY &/ or NATURAL THERAPIES WITH SENSITIVITY TESTS ON THESE CIRCULATING CANCER CELLS. This then establishes the response to a particular Chemotherapy (if this is the intended treatment) and choosing one or more drugs that will actually work instead of the current methods of treating first and assessing the response later, somewhat like taking a blind shot at the cancer!

I have always been very passionate in teaching Doctors and the public to recognize the underlying cause of a disease. This is the only way to win the war against both Non Communicable and Communicable Diseases. Cancer is a good example of this.  We can discuss the preventive and nutritional treatment options in the next article.


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