Post-Partum Depression

We know the cause. We can anticipate PPD and at least, minimise it: let’s do it!

Picture of solitude and introspection: have we missed the PPD?

I did a post on this subject on 11/16/23: the present note is by way of an update, (hopefully) more succinct and of greater clarity, presenting an easier “read”.

Back on November 08, 2023, Medscape News sent me a report by Khushi Mandowara, to the effect that a new pill named Zurzuvae, designed by Biogen-Sage Therapeutics, is available for treating Postpartum Depression.
It seems that Zurzuvae works very well, but the cost for a 14 day treatment will be $15,900 and the treatment may need to be repeated, for a further two weeks!

Background:

In pregnancy, maternal hormone production goes into overdrive: not only are Estradiol (the main Estrogen), Estriol (the most important estrogen during pregnancy) and Progesterone (the “pregnancy hormone”) increased: there is increased DHEA, Testosterone, Thyroxine and particularly, Allopregnanolone, which is derived from Progesterone.

Production of all these hormones begins to fall a couple of days before, and “bottoms out” just after, childbirth. The result for the mother is a sudden, acute hormone deficiency, which may be transient, may persist for a day or two, or may linger, with deficiency of one or more hormones.

Most women, delighted with the delivery of a healthy baby and buoyed by the long-awaited completion of the painful and stressful process which is childbirth, are joyful, although physically exhausted. However some mothers (a significant percentage) become psychologically distressed, to the point of depression.

The incidence of Postpartum depression (PPD) is amazingly variable: according to Ayan Myssayev et al., reporting from the town of Semey in Kazakhstan, the worldwide rate is between 0.5 and 63%! The US rate is approximately 1/10 overall, but is higher, unsurprisingly, among the poor and disadvantaged, those with a prior history of anxiety and/or depression and those subject to adverse environmental conditions, such as air pollution*.

PPD Is due to Allopregnanolone deficiency, and is related to stress. It occurs more frequently when the mother has been anxious, apprehensive, frankly depressed or significantly stressed, during the pregnancy. It is sometimes mild and transient; but often becomes chronic and severe enough to be termed “psychosis”: suicide and infanticide are significant risks. It may begin soon after childbirth, may present In the first few days, or may appear at some point within 12 months following the Birth.

Since the mother goes home within 24 – 48 hours of delivery, the diagnosis is missed in up to 50% of delayed-onset cases.

Treatment with Allopregnanolone relieves PPD quickly, but Allopregnanolone is extraordinarily expensive, only available in very small quantities and must be given intravenously. A synthetic Allopregnanolone, Zulresso, Sage therapeutics’ original product, works well; but it too is an intravenous medication.

Therefore from the standpoint of the Allopathic physician, Biogen-Sage’s “Zurzuvae” is a welcome addition to our drug armamentarium. However it will cost US$15,900, for a 2 week treatment, which may need to be repeated.

Hey, wait a minute!
US$15,900, (C$21,000 940.81) for 14 pills, “repeated”? Surely, there must be an inexpensive workaround!

Couldn’t we anticipate, and prevent, PPD?

If low Allopregnanolone is the cause of PPD, maybe could we simply prevent Allopregnanolone deficiency?

We know that there are production aberrations of multiple hormones just before, and during, childbirth: the active hormones, DHEA, Thyroid 3 (T3), Testosterone, Estrogen, Progesterone and Allopregnanolone all go down, while Cortisol goes up. So why not test mothers for hormone balance, in labour?

Let’s have a look at the hormones – first, how the “steroids” are made from cholesterol, then we’ll consider the hormones, one by one and Finally, we’ll put the whole thing together and figure out how to solve the PPD problem.

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Testosterone and DHEA

Testosterone is just as important for women, as it is for men

Mister T

Testosterone, The Universal Hormone

Although testosterone is called the “male sex hormone” and is at a much higher level in men, it is important to both genders. Everyone needs it, to support muscle, bones, the heart, the personality and the libido. In youth, it is mainly made in the testicles (or ovaries), but all our cells can convert DHEA into testosterone for themselves, by a process which Professor Fernand Labrie  (1) termed “intracrinology”, back in the ‘80s .

Testosterone isn’t simply the main hormone responsible for maintenance and repair of our muscle, bone, skin, sweat glands, hair: it also minimises our anxieties, shields us from depression, supports the libido in both male and female and maintains our self-confidence, encouraging a positive outlook.

Maximum testosterone production, beginning at puberty, is approximately 10 times greater in men, than women. The superhigh testosterone is responsible for the male sex chacteristics – beard and body hair, deepening of the voice by enlargement of the larynx, greater muscle mass, stronger, heavier bones, development of the prostate and the penis and heightened self-confidence (?-Overconfidence?).
In the female, testosterone production is insufficient to stimulate male pattern hair growth, hypertrophy of the larynx and other male characteristics; but it is important nevertheless: it supports self-confidence, self-assurance, cognition and libido, as it does in the male.

Male Testosterone levels

Much of our testosterone supply is produced in peripheral cells, by modification of the DHEA molecule. Therefore, not surprisingly, there is a gradual fall in Testosterone production, paralleling the 1% per year reduction in the DHEA supply, starting at age 26 in both sexes.

In women, the normal serum testosterone at age 20–25 is only 20-30 picomoles per litre, so a 1% loss is easily demonstrated. However the 1%/year downward trend in Testosterone is hard to “see” in men, because their blood level spans a wide range (60–900 pmol/litre) and because the male’s Testosterone level varies, both with the time of day (highest at 8AM) and with physical and sexual activity. *
Here, there is a difference between men and women, because the testicles don’t lose function completely at “andropause”, as the ovaries do at menopause; but by age 80, men’s testosterone production is 10-20% of what it was at 25.

* In the male, the testoterone level often doesn’t match with symptoms: while some men with mid-normal “T” levels present to the MD with Low-T problems, even in their 20s, but many older men with “low T” are fit, sexually active and cognitively sharp,

Female Testosterone levels

Women’s ovaries also produce testosterone in youth, but at menopause they shut down completely. The peripheral cells continue “intracrine” testosterone production, but the amount made depends on the DHEA supply, which varies widely from person to person. A relatively small percentage of women approach the 30 pmol/litre “normal” upper limit of serum testosterone in the third decade, a surprising number of young women suffer from extremely low testosterone levels and in post-menopausal women, serum Testosterone tends towards zero.

In contrast to the male’s experience, reduced testosterone level in the female tends to be symptomatic, since it is always associated with DHEA deficiency and often, with intracellular hypothyroidism (IH). The “low testosterone syndrome” (my terminology) in women usually begins at age 26 – 30, but may be symptomatic by age 20.
It often presents in combination with a mixture of low testosterone and hypothyroid symptoms and signs: hair loss, brittle fingernails, dry skin, vaginal dryness, reduced self-confidence, low libido, “fuzzy thinking”, weight gain, poor glucose and cholesterol management, etc..

The syndrome, often seen in 20-to-30-year-old women, usually responds quickly and well, to oral supplementation of DHEA: if it does not, thyroid tests should be done, including TSH, FT4, FT3 and T3, so as to diagnose or exclude IH, which is easily and safely treated with slow-release triiodothyronine.

Childhood Stress and “The Troubled Teen”

A frank episode of PTSD, chronic neglect, abuse or a subjective perception of inequity and unfairness in the family dynamic, is sufficient to stress a child to the point where he or she begins to overproduce the stress hormone, cortisol.

The hypercortisolism, usually unrecognised, is associated with reduced DHEA and intracellular hypothyroidism and may persist into and throughout the teenage years. The reduced availability of serum T3, due to IH, results in dysregulation of brown fat function, leading to inefficient calorie, glucose and cholesterol management. The “picture” is one of obesity, pre-diabetes, hypercholesterolemia and possibly, other metabolic problems, as a result of which some individuals begin the 3rd decade “behind the 8 ball”.

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Magnesium

Calcium-based bones support your frame, but magnesium supports your chemistry: could it help with ED?

A recent (2023) news-feed included a report, entitled “A higher dose of Magnesium (Mg) each day keeps dementia at bay”: the report, based on an article from the Neuroimaging and Brain Lab of the Australian National University (ANU), condensed the article into the following statement: “The brain age of people consuming more than 550mg of Mg daily is about a year younger at age 55, than that of people with a normal Mg intake of about 350mg per day”.

The article, entitled “Dietary magnesium intake is related to larger brain volumes and lower white matter lesions with notable sex differences”, by Khawlah Alateeq, Erin Walsh and Nicolas Cherbuin, DOI: 10.1007/s00394-023-03123-x, was published by Research Gate on 3/10/23 and reported by europepmcc.org,  NIH and the European Journal of Nutrition.
The study involved more than 6,000 cognitively healthy subjects in the UK, aged 40-73: it concluded that higher dietary Magnesium intake is related to better brain health in the general population, particularly in women.

Not being either a mathematician or a gifted statistician, I cannot pretend to understand the mathematical logic, but I’m prepared to accept the (quite reasonable) conclusions, that magnesium is necessary to brain health and that we should try to ensure that no one is magnesium-deficient.

The article reminded me that magnesium is indeed a top-level concern in the management of the human body and that as a topic for discussion it is eminently worthy of inclusion in my blog.

MAGNESIUM (Mg)

Graphic courtesy of Wikipedia

Mg is a shiny, gray metal whose atomic nucleus contains 12 protons (atomic number 12). It is lighter than Aluminum and is used primarily as a component in strong, light-weight aluminium alloys. It has a low melting point (650°C) and is so chemically reactive that in its natural state, it is only found in combination with other elements. Magnesium is so reactive with oxygen that it burns in air (with a brilliant, white light) and when isolated, the “pure” metal has a thin, external layer of magnesium oxide, because its exposed surface reacts instantly with oxygen in the air.

Magnesium is the fourth most common element in the Earth as a whole and is the eighth commonest element in the crust (iron, oxygen and silicon are more abundant). Although it is even lighter than Aluminum, there is so much magnesium on earth that it accounts for 13% of the planet’s mass and it is in third place, after sodium and chlorine, among the elements dissolved in seawater.

Not surprisingly, this ubiquitous, hyper-reactive element, eleventh by mass in the human body, is active in all our cells and is essential to some 300 enzymes. Magnesium ions interact with polyphosphate compounds such as ATP, DNA, and RNA and they take part in almost all chemical reactions in our bodies. Magnesium compounds are used medicinally as laxatives and antacids (like milk of magnesia), to stabilize nerve excitation and blood vessel spasm (in conditions like eclampsia).

An essential, but often deficient, nutrient

This article reminded me that magnesium is an essential nutrient, of prime importance in our bodies and that as such, it deserves a place in this blog. It is a major constituent in grains, fruits and nuts (especially, almonds); but because the fields on which our food is grown have become magnesium-deficient over time, insufficient magnesium intake is very common in humans: anyone who has constipation and (or) muscle cramps is probably either hypothyroid, or short of magnesium.

Magnesium is an essential nutrient for normal body functions: after potassium, it is the second most common metal in the body, with half in the soft tissue cells and half stored in bone. Very little exists in the blood, which contains only 0.3% of the total Mg in the body. A clue to its importance is that its concentration is tightly controlled: the stores in the bones are used to buffer the concentration in the blood, so blood levels of magnesium only rarely deviate from the normal range.

A very active factor

Mg is involved in about 350 biochemical processes (80% of body processes), and activates many intracellular enzymes.
It is important for protein synthesis, membrane stabilization, antibody activity and immune response.
It helps to build strong bones, but paradoxically, is active in preventing calcification of arteries and in removal of calcium from their lining in cases of arteriosclerosis (a combination of Magnesium, Lysine or Carnitine, Vitamin C, Vitamin D, Vitamin K2-7 and Citric Acid has been recommended, for treatment of calcific arteriosclerosis (not atherosclerosis).   

Magnesium deficiency

In young people, the small intestine absorbs 30–50% of the Mg in the diet, but the percentage diminishes in old age, chronic Kidney disease and increasing intake.
Also, the magnesium content of farm soils has been eroded over time due to intensive cultivation without replacement of the metal.
In any event, Mg deficiency is endemic, so the symptoms and signs of low magnesium are common.

Conditions due to magnesium deficiency

High blood pressure, arteriosclerosis, heart disease, diabetes, osteoporosis and bone fractures, migraine, asthma, constipation and chronic kidney disease, fatigue, tiredness and weakness are all associated with low magnesium.

The commonest complaints are:

Constipation

Calcium is necessary for muscle contraction and magnesium, for muscle relaxation. So if the Mg is low, the muscles of the large intestine are unable to relax, to accept bowel contents coming from above. Therefore movement of stool towards the rectum slows down, water absorption by the lower bowel (the sigmoid colon) dries it out and the waste becomes very difficult to move.

Muscle cramps

Although magnesium deficiency has been blamed for muscle cramps, no direct association has been proven and taking Mg does not necessarily prevent cramping.

Hip fracture: lower serum Mg levels are associated with an increased risk of fractures: the assessment for osteoporosis should include checking magnesium levels and part of the treatment should be Mg supplementation.

Poor response to brain injury: Brain swelling from injury and in neurological diseases is associated with low Cerebral Mg concentration: giving magnesium reduces brain swelling, restores the ability of the blood-brain barrier to keep toxins out and improves the speed and efficiency of healing. It may be that in brain injury and neurological diseases, a low Mg level is part of the reason for brain swelling and slow recovery.

Vascular calcification (VC, arteriosclerosis)

Commoner in patients with chronic kidney disease (CKD) and especially in those on dialysis, magnesium deficiency contributes to the risk of cardiovascular disease (CVD).

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