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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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Datuk Dr Selvam Rengasamy MBBS, FRCOG,

Fasting has been a religious practice for centuries in most cultures. Medical profession which has been always focussing on the caloric intake and regular meals has now accepted that fasting improves health.

Traditionally fasting is observed during religious festivals, according to lunar calendar days, auspicious days as an offering to God & self purification. This is done in many ways, from eating one vegetarian meal a day anywhere from 21days and onwards to total abstinence from food for an entire day.

There are many variations to this practice in different cultures. When fasting is observed for 2-4 days, various medical benefits have been observed as shown by a recent University of Southern California study. A shorter, 24 hour fasting can be beneficial as well. This study as well as many other studies have shown the following benefits of fasting:

1: A powerful anti aging effect

  1. Immune stimulating effect
  2. Stem cell activation
  3. A powerful protection against Cancer cell proliferation by lowering Insulin levels. Cancer cell proliferation occurs in the presence of Glucose and Insulin. It should be noted that Insulin is a Proliferative hormone and that means it increases the rate of cell division!

Let’s talk about Intermittent Fasting which has caught the medical attention recently. Intermittent Fasting has also been in practice in many cultures for ages. My father who found his way to where he started at the age of 93 was a very spiritual person. He used to fast with one meal a day for 21 days from the time I can remember before religious rites at Hindu and Buddhist temples. He was healthy till his last days only succumbing to the divine call.

There are variations in the Intermittent Fasting. The difference is in the number of hours that you can eat and the number of hours that you need to fast. There is also some difference in what you can eat. Although it is often advised that you can eat whatever you want for the certain number of hours, it is prudent to watch THE CARBOHYDRATE INTAKE AS IT WILL STIMULATE INSULIN PRODUCTION & RELEASE.

My advise has always been a diet that comprises of PLENTY OF FRESH VEGETABLES, LOW CARBS  WITH GOOD FATS & PROTEINS. Better results can be seen when you limit your eating hours to 8 and fasting hours to 16 making up a day of 24 hours. The window of eating is entirely up to you which means you are at your own liberty to start eating at any time as long as you close the window within 8 hrs. The 16 hrs of fasting will not be difficult with hunger and food cravings as long as you choose the timing smartly and always have more vegetables and good fats and moderate amount of protein in your diet. It is the carbs that makes you feel hungry soon after meals.

“It is the decision that you make today involving changes in the way you live that decides your destiny .”

Towards Better Health for All.

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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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Datuk Dr Selvam Rengasamy MBBS, FRCOG,

Aging is a multi factorial &  an inevitable biological process that happens to all of us. Multiple  reasons are often present in any one person . While we cannot stop the aging process, we can certainly slow it down & even reverse it to a certain degree. This is the normal aging process which is under our control. However the concern now is the ACCELERATED AGING that we face in most of us. Poor diet, Hormone Deficiencies, Toxic Overload, Nutritional Deficiencies, Hyperinsulinemia are some of the common causes.

However CHRONIC INFLAMMATION is the main player. Understanding and controlling Chronic Inflammation is necessary not only to control aging, but also to win the war against almost all the known medical conditions. Chronic Inflammation occurs silently due to many reasons . Sugars , Refined Foods, Gut Dysbiosis,  Heavy Metal & Environmental Toxicity are the main culprits. Managing and silencing this silent inflammation need to be addressed seriously. There are many natural healing remedies that can help, such as Omega 3 EFAs, Curcumin, Vitamin C, Quercetin etc. While all of them help and a combination will even work better, let me focus on Omega 3 Fatty Acids especially from fish.

While traditionally the well known benefits of fish oils for the Heart, Brain and Joints is a common knowledge, new studies shows many more benefits. The main benefits of fish oils are due to their Anti Inflammatory effects. Omega 3 suppresses all the arms of inflammation esp. the NFkB & IL6 .Giving a dose of 2 gm per day brings in clinical benefits within weeks of commencing treatment. Higher doses may be necessary in acute conditions and fish oil is safe even in larger doses. Let’s look at what is new:

  1. Protectins & Resolvins are wonder molecules that our body produces to control runaway    inflammation and this helps to slow down aging. Omega 3 boosts the level of both these molecules.
  1. Aging is associated with a lot of wear & tear. Accelerated healing means the ability to heal quickly, resulting in preserving & improving cell / organ functions. Rapid healing of cell injury can promote  Robust heath & wellbeing. Omega 3 helps in repair of damaged tissues.
  1.   Inflammation increases Calcium deposition in the arteries, stiffening them and reducing the blood flow to tissues. Omega 3 reduces extraosseous Calcium deposition.
  1. Keeps muscles young & healthy. 2 gm/ day helps to reduce age related loss in muscle mass & function.
  1. Consumption of Omega 3 during pregnancy leads to improved brain function & IQ in children.
  1. Study at Laboratory of Molecular Signalling has shown that besides improving Memory & the ability to learn new things, Omega 3 is necessary for growing new neurons enabling higher level of executive function & multitasking.
  1. Omega 3 is a potent stimulator of Nitric Oxide synthesis. Nitric Oxide not only improves Heart & Vascular Function as well  as Sexual health, but  also  improves  Immune Function, promotes Lipolysis ( even without controlling diet ) , promotes strong muscles. By the age of 70, we have 75% less N.O in our body.
  1. More than 40 studies have shown a beneficial effect of Omega 3 in Triglyceride levels.
  1. Omega 3 maintains DNA health by slowing down the age related (accelerated) Telomere shortening as well as reversing the shortened Telomeres. This has a profound effect on aging & diseases.
  1. Besides improving joint health, Omega 3 also helps in improving vision by reducing Age Related Macular Degeneration.
  1. While regular , moderate, unprotected sun exposure is extremely vital for health, sun exposure in the presence of Omega 3 deficiency increases oxidative stress to the skin and promotes early onset wrinkles

There are other benefits to omega 3 EFA as well. Though Fish Oil is the best source of Omega 3, the fish should be cold water wild caught fish for the best benefits. Some Fish oil manufacturers also offer molecularly distilled pure oils, certified by the International Fish Oil Standards. Vegetarians could choose to take Flaxseed Oil. Chia seeds also have omega 3 but this is not a rich source. In order to get adequate amounts of Omega 3 for its Anti inflammatory and other benefits, one has to consume fish at least 3-4 times a week or about 3 pounds of fish a week. This is tough for most making supplementation necessary.

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Datuk Dr Selvam Rengasamy MBBS, FRCOG,

I was on my way to the Heathrow Airport when I received frantic messages from someone who is in her 60s who I knew was desperate for answers . Let’s call her Miss PK. She had a mastectomy for breast cancer 10 years ago. Not surprisingly, she was also treated with a concoction of chemotherapy and radiotherapy. As usual PK’s concoction had an added ingredient, an anti-estrogen.  Most of you who have been trained by SAHAMM by now would have realized that something is very wrong here . Leaving the root cause of her  disease, her excess Estrogen untouched. There was no Progesterone in her treatment basket to oppose the Estrogenic effects. The reason?. She was advised against Progesterone based on her receptor status. I could not convince her to reconsider.

Honestly, I strongly believe that all excess Estrogen must be opposed by Natural Progesterone.  Six months ago, PK called for advise for her post menopausal staining. Ultrasound showed Endometrial Hyperplasia which again pointed to excess Estrogen. We discussed about Progesterone once more, but she became silent again.  May be I was not convincing enough or perhaps because the advice was given free!.

Coming back to the  frantic messages, PK had fresh vaginal bleeding. Ultrasound this time around showed what appeared to be an Endometrial Polyp. She was advised to have a DD&C followed by a Hysterectomy . She was frantic and I felt sorry for her. She sought my advice if she should proceed with a hysterectomy straight away rather than doing a DD&C first. It makes sense to do that or at least an on table endometrial scrape and proceed for Hysterectomy if the curettage looked suspicious. I insisted that irrespective of what she gets done (of course I would prefer to give Progesterone before any surgical procedure and continue afterwards) she needs to consider Progesterone replacement .

Rings a bell?  We all too often have faced this situation where a woman who has had treatment for either a benign or malignant tumour of her Breasts, Ovaries or her Uterus only to have a recurrence because the UNDERLYING PATHOLOGY WAS NEVER ADDRESSED.  ALL BENIGN & MALIGNANT TUMORS IN THESE ORGANS ARE DUE TO EXCESS ESTROGEN & PROGESTERONE DEFICIENCY! THEY ARE NOT DEFICIENT IN CHEMO DRUGS, RADIOTHERAPY or ANTI-ESTROGENS!

My advise to all those  who are reading this article is ALWAYS TREAT THE ROOT CAUSE(S) FOR ANY DISEASE with a natural, holistic and integrative approach and paying attention to all the pillars of health.

Recently a double blind, randomized study involving 208 postmenopausal  obese and overweight women with Vitamin D deficiency was done. The women were divided into 2 groups. All of them were put on a weight reduction Programme. One half of them were given Vitamin D 2000iu daily while the other half was given a placebo. Follow up analysis clearly showed that the supplement group had a significant reduction in cancers compared to the placebo group even when the weight reduction was taken into account . Many studies have shown that Vitamin D helps to reduce the Estrogen levels in the body, a fact that should draw the attention of men as well to reduce their Estrogen dependent Prostate and Breast cancers. It is interesting to note that Vitamin D levels are often low in overweight and obese people due to its sequestration in fat cells .

Vitamin D works better when combined with Vitamin K2.

Have a blessed day.

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