This just in (November 08, 2023), from Medscape news – A report, by Khushi Mandowara: a Biogen-Sage Therapeutics pill called Zurzuvae, is available for treating Postpartum Depression.
Zurzuvae will cost $15,900, for a 14 day treatment, which may need to be repeated.
Background:
In pregnancy, maternal hormone production goes into overdrive. Not only are Estradiol (the main Estrogen), Estriol (the main estrogen of pregnancy) and Progesterone (the“pregnancy hormone”), increased: DHEA, Testosterone, Thyroid Hormone and particularly, Allopregnanolone (the brain hormone), all increase.
Production of these hormones reduces a couple of days before delivery and “hits bottom” after childbirth.
The result 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, many mothers become psychologically distressed, some to the point of becoming deeply depressed.
Depression following childbirth tends to be so severe and so difficult to treat that it has been given its own name: “postpartum depression” (PPD). The incidence of PPD is amazingly high, and there is a huge variation from country to country and from city, to city. For example, according to Ayan Myssayev et al., reporting from Semey, a city in Kazakhstan, the worldwide rate is between 0.5 and 63%!
The rate in North America is approximately 1/10 overall: higher, in high stress situations. Unsurprisingly, 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, are at greater risk.*
According to Lacey Chavis, Psy,D., of Johns Hopkins,
1/3 of women with Postpartum depression had a premonition of the problem, during the pregnancy.
1/3 women with PPD present immediately postpartum.
1/3 present within a year of delivery.
Further, 3/4 women with PPD are untreated.
What causes postpartum depression?
Postpartum Depression (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, but is often severe enough to constitute a psychosis: suicide and infanticide are significant risks.
When does it start?
PPD may begin soon after childbirth, start after a few days, or appear at some point within the first 12 months after the baby is born. Since the mother goes home within 24 – 48 hours of delivery, the diagnosis is missed in up to 50% of delayed cases.
Treatment, for PPD
Treatment with Allopregnanolone relieves Postpartum depression quickly, but Allopregnanolone is extraordinarily expensive, only available in very small quantities and must be given intravenously.
A synthetic Allopregnanolone, Zulresso, from Sage therapeutics, works well; but it too is an intravenous medication. Its yearly cost is US$34,000.
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!
What?
US$15,900, (C$21,000 940.81) for 14 pills, “repeated”?
Is there an inexpensive workaround which will prevent, or alleviate, PPD?
Allopregnanolone deficiency is uniformly present in PPD and PPD is reliably responsive to Allopregnanolone administration. Therefore depressed mental health during and after parturition must be a hormone – dependent condition.
Also, we know that the levels of multiple hormones change abruptly during and after childbirth and that hormones, particularly the brain’s neurohormones, are interdependent: the production rate and blood level of each hormone may rise, or fall, in response to changes in other hormones.
So let’s have a look at maternal hormone balance, before and during pregnancy, during childbirth and thereafter, to see whether there may be hormonal swings which may be causing PPD: in that case, PPD should be amenable to treatment via hormone therapy. Possibly, we might arrive at an alternative method of treating Postpartum depression, which the uninsured poor could take advantage of.
Let’s think about the hormones of pregnancy, one by one; but first, we need to review the origins of maternal hormones and the changes which occur at parturition.
MATERNAL HORMONES, and HORMONAL CHANGES, DURING and AFTER CHILDBIRTH:
How the Neurosteroids (the “brain hormones”) are made
Neurosteroid hormone generation begins with cholesterol, which is modified to produce Pregnenolone. Pregnenolone is processed into Progesterone, DHEA and Cortisol.
This sequence of chemical changes takes place in the brain; but also, in the adrenal glands.
Allopregnanolone (below) is not represented in this graphic.
(1) DHEA
DHEA is the source of Testosterone, Oestriol, Estradiol, Progesterone and an individual mixture of “micro-hormones”, which varies with the function of the cell.
In humans, DHEA is produced ad libitum, with no feedback control, up to age 25, which was our prehistoric life expectancy. Then by age 26, adrenal production of DHEA begins to subside, falling by 1% per year (figure 1). Production may be compromised much earlier, in those who have been subject to significant stress.
DHEA is produced by the brains of all vertebrates. In Primates, the adrenals produce huge amounts of DHEA, with no feedback mechanism to interfere with production. Therefore DHEA, in unlimited quantity, is available to all cells in the body. Each cell uses DHEA to produce a mix of “downstream hormones”: each cell has its own, individual “hormone recipe”, which it needs to function normally. At age 26, humans begin to reduce DHEA production, 1% per year, so that by age 80, our DHEA levels are 10 – 20% of what they were at age 25.
For the best-ever graphic of DHEA decline in humans, and to read Dr. J.W. Nyce’s wonderful article, see HERE.
Thus, maternal DHEA is often deficient before conception, but rises rapidly once pregnancy begins and continues at a high level throughout pregnancy. Production is reduced just before the baby is born and returns to the mother’s baseline level (which may be subnormal) following parturition.
A deficiency of DHEA leads to deficiency of hormones derived from it. Deficiency also causes Hypothyroidism inside the cells, in this roundabout way: DHEA suppresses cortisol production, so when there isn’t enough DHEA, excess cortisol is produced. Maternal cortisol production is high throughout pregnancy and many women increase their cortisol during delivery, because of stress.
(2) Progesterone
This “multitalented” hormone performs many duties in the body, including production of Allopregnanolone for brain maintenance and repair. It is viewed as “the pregnancy hormone”, because it is necessary for implantation of the ovum and the growth of the fetal brain.
Progesterone can be changed into “mineralocorticoids”, which tell the kidneys how much salt and other chemicals to excrete into the urine, but also, it is the raw material for Allopregnanolone, which is the brain’s main maintenance and repair hormone.
Deficiency of progesterone is the commonest cause of PMS, may cause infertility and in the first 8 weeks of pregnancy can result in spontaneous abortion.
The placenta produces Progesterone in increasing quantities, so it, and Allopregnanolone, increase to maximum during pregnancy and fall precipitously when the placenta is jettisoned.
(3) Cortisol
The baby, also stressed by birthing, increases production of ACTH (AdrenoCorticoTrophicHormone), to call for extra cortisol: fetal ACTH crosses the placenta to the mother’s bloodstream and stimulates her adrenals to produce more cortisol. The high level of cortisol results in:
(1) Blockade of conversion of T4 hormone into active T3 and destruction of pre-existing T3, in the cells.
(2) Conversion of T4 into nonfunctional “reverse T3”.
The result is “T3 starvation”and reduced efficiency of all maternal systems, including psychological and cognitive functions.
(4) ALLOPREGNANOLONE:
Cholesterol is used to make Progesterone, which is reliably converted into Allopregnanolone. This process is boosted by PalmitoylEthanolAmide (PEA), found in many foods (notably, peanuts), Vitamin D3 and fish oils.
Allopregnanolone is the brain’s main “housekeeping” hormone. It has been described as “stress reducing, rewarding, prosocial, anti-aggressive, pro-sexual, sedative, sleep facilitating, pro cognitive, memory enhancing, analgesic, anticonvulsant, neuroprotective and neurogenic” (Wikipedia).
Allopregnanolone is essential for sleep, mood, “happiness”, endorphin (painkiller) production and brain maintenance. It is a major factor in the development of the baby’s brain. Maternal Allopregnanolone is maximized during pregnancy; but when the placenta disconnects from the uterus after birth, progesterone production stops and Allopregnanolone plunges.
In childbirth, Beta-endorphins (painkilling chemicals), generated from Allopregnanolone, rise, reach a peak during delivery, and decline after parturition. High endorphin levels during labor and birth can produce an altered state of consciousness, helping the mother to cope with labour. High endorphin levels can also increase alertness and at times, produce euphoria, after birth.
In this early postpartum period endorphins, together with oxytocin, encourage mother-infant bonding. (4)
Allopregnanolone deficiency is responsible for devastating maternal postpartum depression.
(5) Testosterone
Testosterone is responsible for heightened self-confidence and reduced anxiety. It is made from DHEA and can approach zero when DHEA is deficient (in my practice I saw several women, aged less than 30 years, with zero Testosterone). Testosterone increases by up to 70% during pregnancy and returns to baseline after the baby’s birth. Paradoxically, some investigators have reported “higher levels of testosterone” and have related an increase in both anxiety and anger, to “elevated maternal testosterone levels in the postpartum period”. This is counterintuitive: it is unlikely that a human, deficient in DHEA, would generate enough testosterone to make her angry (see my note regarding this, under “risk factors for PPD”, below).
(6) Estradiol
Estradiol is important for bone, muscles and skin in both mother and fetus, rises slowly in the first and second trimesters, is steady in the third trimester and decreases rapidly when the baby is delivered.
(7) Estriol
Estriol is the gentlest of the three human estrogens. It is almost undetectable while the menstrual cycle is active. In pregnancy however it is essential for both the mother and the fetus, especially because it promotes blood vessel growth, both in the rapidly enlarging uterus and in the fetus. It is made by the placenta and begins to rise in the 8th week of pregnancy, increases as the placenta grows and remains at a high level throughout pregnancy. After birth, it also returns to baseline.
(8) Thyroxine
T4, from the thyroid gland, is converted into Triiodothyronine (T3) by “Deiodinase 1”, an enzyme present in all cells in the body except for the pituitary gland (the pituitary uses a different enzyme, Deiodinase 2).
T4 production increases slightly during pregnancy. If the mother is free of psychological, physical or metabolic stress, conversion of T4 to T3 within the cells progresses normally, facilitated by the increased DHEA. However if and when she is stressed, the resulting surge of cortisol blocks T4 conversion to T3, leading to intracellular T3 deficiency.
(9) T3
T3, the indispensable, active thyroid hormone, is responsible for efficient function in all cells. If T3 is deficient before conception, implantation of the ovum in the uterus may fail. Furthermore, maternal T3 deficiency in the first 6–8 weeks of pregnancy, whether due to true hypothyroidism or to stress-related intracellular hypothyroidism, can cause spontaneous abortion.
An adequate supply of T3 is essential to the baby, for normal development of all organs, particularly the brain and nerves.
The fetus does not achieve full thyroid function until 20 weeks of pregnancy, so its supply of T3 is dependent on sufficient T3 crossing the placenta, from the mother’s bloodstream. If the mother’s free T3 is low, the fetus will be hypothyroid while its brain is developing and while neuronal connections are in process.
Maternal stress-related T3 deficiency between the eighth and twentieth week, with fetal hypothyroidism and subtle aberrations of fetal nerve connections, is associated with an increased rate of autism, schizophrenia, gender dysphoria and reduced cognitive ability.
Not surprisingly, it has been observed that maternal depression, or anxiety, early in pregnancy is associated with lower scores on the Bayley Scales of Infant Development (BSID, an index of infant cognition) at 12 months of age. This, to my mind, confirms an episode of maternal intracellular hypothyroidism between the 8th and 20th week of pregnancy, which could have been treated effectively with oral, slow-release triiodothyronine, if it had been diagnosed.
Therefore Caveat!
In the first half of its stay in the womb, the fetus is dependent on a supply of maternal T3. All fetal systems, including the brain, will be impacted by hypothyroidism, if the mother’s serum T3 is too low. Therefore, in a perfect world, TSH, Free T4, Free T3 and reverse T3 would be checked before conception, or failing that, a “thyroid profile” would be obtained as part of the initial assessment of pregnancy and any diagnosed free T3 deficiency would be proactively treated.
(10) HCG
At about 4 weeks of gestation,Human Growth Hormone rises sharply, reaching a maximum at the end of the first trimester and subsiding thereafter. By the time of delivery, it is almost back to its baseline.
(11) Oxytocin
Produced in the hypothalamus, oxytocin passes through tiny tubes, to the pituitary gland. The posterior pituitary then secretes it when birth is about to begin. It stimulates the uterus to contract, to expel the baby and to prevent excessive bleeding. Also, it prepares the breasts for milk production and it generates the “warm and fuzzy”, maternal feeling which encourages bonding with the new baby.
(12) Cortisol
The stress hormone, cortisol, is normally secreted in diurnal rhythm, with low levels at waking and increased production in the afternoon. Under normal conditions the quantity produced is small. Maternal cortisol is elevated, 2-4 fold, throughout pregnancy. It tends to cross the placenta to the fetus, but during pregnancy the placenta controls the fetal cortisol level, using a special enzyme to inactivate it.
The stress of parturition leads to a surge of maternal cortisol, enhanced by fetal production of ACTH; but the blood level subsides within 3-4 days after delivery of the baby.
The effect of cortisol on the baby is complicated, and difficult to explain narratively (see table 1). However in one interesting study, a comparison of maternal and cord blood immediately after delivery showed normal maternal TSH, T4, T3 and reverse T3, while in the cord blood, TSH was higher, T4 was approximately the same, T3 was low and reverse T3 was higher: I interpret this as some degree of intracellular hypothyroidism in the baby’s system, but normal maternal function in the cases which were being reported.
Cortisol level and its effects, in parturition
| Maternal | Fetal | Baby’s 1st year | Result |
| Hi cortisol trimester 1 | ? Hypothyroid | Slo fetal development | Reduced cognition |
| High cortisol trimester 3 | Placenta cancels Cortisol | Rapid development | Cognition normal |
| High cortisol in labour | Hi cortisol in labour | ||
| Cortisol normal in 4 days | |||
| Normal T3 & T4, Low rT3 | High TSH, N T4, Low T3, Very High rT3 | ||
| Low T3, high rT3 | IH, PPD, Fatigue |
“Baby blues”
The postpartum mother is immediately subjected to Progesterone and Allopregnanolone deficiency, high Cortisol, low Estrogen, low Testosterone and “T3 hormone starvation” inside her cells. If she is “in a happy place” and unstressed, recovery begins: endorphins derived from Allopregnanolone produce euphoria, anxiety and apprehension fade away, cortisol subsides quickly, and resumption of intracellular T3 generation restores cellular efficiency, with beneficial effects on mood and cognition: the “baby blues” subside, sometimes immediately and sometimes, within 3 or 4 days.
If the mother is in a high-stress situation, if she tended to be depressed previously, or if she is anxious for some reason (especially if her DHEA/Testosterone and Progesterone/Allopregnanolone production is poor), the cortisol level will remain high and intracellular hypothyroidism will persist. Her postpartum fatigue will linger, she may experience confusion and the stage will be set for postpartum depression. An immediate diagnosis of IH, with or without DHEA and Progesterone deficiency, will facilitate a decision to treat. It is therefore important to assess the mother’s hormonal balance, within 24 – 48 hours following delivery.
Signs of postpartum depression may include:
- Inability to perform basic activities of daily living
- Introversion
- Unexplained Anxiety
- Feeling overwhelmed
- Melancholy
- Extreme fatigue
Assessment, Prediction and Prevention of postpartum depression
Routine reassessment of maternal metabolic and hormonal balance should be scheduled for 24 to 48 hours postpartum: in addition to the usual CBC, kidney and liver tests, cholesterol etc., the DHEA, Testosterone, Estradiol, Progesterone’s and a “full thyroid profile” should be assessed. The thyroid profile must include TSH, FT4, FT3 and reverse T3 estimations (as to its derive the T3/rT3 ratio, which is diagnostic of intracellular hypothyroidism, Vs. a state of normal thyroid balance.
Since PPD may develop at any point within a year of parturition, it would be wisest to reassess all of these blood studies at 3, 6, 9 and 12 months after parturition. Deficiency of DHEA or Testosterone should be treated with oral DHEA. Estrogen/Progesterone imbalance is easily managed with therapeutic creams (taking care not to transfer cream to the child).
True hypothyroidism can be treated as usual, with thyroxine; but for Intracellular Hypothyroidism, oral T3 is necessary: prescription of thyroxine in the presence of IH results in” failure to cure” and heightened hypothyroid symptoms.
Doubtless, in a percentage of cases the patient’s home and societal conditions will render the situation unmanageable: psychological and psychiatric care may be necessary for some.
The postpartum period lasts for six to twelve weeks after birth of the baby: lochia stops and vaginal/perineal discomfort subsides. However, decreased estrogen levels postpartum may result in changes to the genital tissues, with thinning mucosa and vaginal dryness. This can continue even later than 6 weeks postpartum.
Depression is the most common psychiatric problem during pregnancy, affecting more than 13% of pregnant women, so diagnosing and treating it is prime. Antenatal depression is a harbinger of PPD and should trigger a reassessment of hormonal balance, including a thyroid profile.
Currently, there is concern regarding the safety of antidepressants: psychopathy is a possible side effect. The side effects of psychoactive drugs should taken into account. When dealing with either antepartum or postpartum depression, it is mandatory to weigh the risks of pharmacological treatment versus the risk involved in leaving the patient untreated.
“The Baby Blues”
In identifying PPD, it is important to exclude postpartum “baby blues”, defined as a mild transient dysphoria occurring in the first week after delivery, which is observed in 50 to 80% of new mothers. This as likely as not, is due to temporary stress-related intracellular hypothyroidism and will need no treatment if it subsides. This possibility does not negate the value of a hormonal assessment within the first 48 hours postpartum, because it is useful to know whether or not the particular patient is susceptible to IH. Once the T3/rT3 ratio has established the diagnosis the T3 level, by itself, will give an indication as to whether IH regresses, or persists.
Pharmacological treatment
Postpartum depression must be diagnosed ASAP and once made, the diagnosis should not be ignored, if only to obviate suicide and infanticide. However SSRIs, including Fluoxetine, Citalopram and Venlafaxine, have been found in mother’s milk and at times, produce adverse effects in the baby: a trial of therapy via hormonal supplements should be instituted before deciding on pharmacological therapy.
Risk factors for PPD
PMS: since PMS is usually due to progesterone deficiency and since progesterone levels plunge at delivery, postpartum progesterone deficiency, with attendant Allopregnanolone deficiency, is probable and PPD is to be expected.
DHEA deficiency: DHEA levels of <5 µmol/litre (female normal is 8 – 11) are uniformly accompanied by low-Testosterone and hypothyroid symptoms. If the DHEA level is less than 8 (this will include a majority of people over the age of 25 years), DHEA should be supplemented per os: the standard dosage is 50 mg per day, but response is variable and the dose may need to be reduced, or increased.
Testosterone deficiency: the upper limit of normal testosterone in the female being 30 Umol/litre, DHEA should be prescribed, sufficient to keep the testosterone level between 20 and 30 Pmol/litre.
“High testosterone”: in an article entitled “High serum testosterone levels during postpartum period are associated with postpartum depression”, in A J Psych, 2015 Oct:17:85-8, doi: 10.1016/j.ajp.2015.08.008, PMID: 26372084, A Aswathi , Soundravally Rajendiren , Archana Nimesh, R Ravi Philip, Shivanand Kattimani, D Jayalakshmi, P H Ananthanarayanan, Pooja Dhiman reported as follows (quote)
“The hormones estimated in these two groups included Estradiol, Progesterone And Testosterone. Their levels were compared. Significantly high testosterone levels were observed in cases of postpartum depression at 24-28h when compared to controls. Estradiol and progesterone levels did not show significant difference between cases and controls. ROC analysis done at 24-28h showed that testosterone levels beyond 42.71ng/mL predict the development of PPD with 79% sensitivity, 63% specificity, 68% positive predictive value, 74% negative predictive value with AUC being 0.708. This study shows that there is an association between persistent high serum testosterone level in women following childbirth and PPD.” ………(end quote)
I am unable to comment on this: it appears that Aswathi et al. meant that the Postpartum depression group had higher testosterone levels than the controls. However, Google has it that the normal female testosterone level lies between 0.10 and 0.90 ng/mL. Therefore “testosterone levels beyond 42.71 ng/ML” is difficult to visualise and interpret.
Estrogen deficiency: this is unlikely to present a problem. A more likely scenario is estrogen excess (a progesterone/estradiol ratio of less than 200), which is easily treated with oral progesterone.
Pre-existing true, or intracellular, hypothyroidism, which can present with fatigue (akin to chronic fatigue syndrome), depressed mood, reduced cognitive ability (fuzzy thinking), mood swings, apparent infertility, recurrent abortion or other, relatively minor hypothyroid symptoms, is easily diagnosed by means of the “full thyroid profile”, as above and safely treated with (titrated) triiodothyronine.
Coexisting diagnoses
Hypercholesterolemia, Prediabetes, Metabolic Syndrome, coincident with IH: IH should be treated as a prerequisite to therapy, since often, the Triiodothyronine prescription will normalise elevated cholesterol and A1c levels.
Dietary supplements
Palmitoyl Ethanolamide (PEA), present in many foods but particularly in peanuts, has been shown to raise Allopregnanolone levels and perhaps, should be recommended for all women in the last week of pregnancy and for a month or more following parturition.
Pregnenolone, since it is a progesterone precursor, is recommended.
Oral Progesterone can be very helpful, if the serum progesterone level is substandard.
Vitamin D3 and fish oils may help.
THE BOTTOM LINE, on POSTPARTUM DEPRESSION
Postpartum depression is devastating and its prevalence is frightening: an NNT (number–needed–to–treat, to achieve one cure) of 10 (or less) renders it, one would think, mandatory to institute a preventive care program, to achieve maximal diagnostic efficiency and desirable prevention and cure rates.
Preventive care, as outlined above, would be simple and would add very little to the cost of diagnosis. Prevention of PPD will be a lot less costly, than cure!
There are several supplements that may help increase allopregnanolone production:
- Pregnenolone: This is a precursor to Progesterone, so supplementation may indirectly increase allopregnanolone levels12.
- Vitamin D3: Low levels of vitamin D3 have been linked to depression, anxiety, and other mood disorders. Supplementing with vitamin D3 may help increase allopregnanolone levels2.
- Etifoxine: This is a Russian anxiolytic that has been suggested to increase allopregnanolone levels1.
- Progesterone: Taking progesterone can reliably increase allopregnanolone levels in the brain3.
- PEA (PalmitoylEthanolAmide): This supplement can also boost allopregnanolone3. peanuts contain more PEA than any other food.
Please consult with a healthcare provider before starting any new supplement regimen. It’s also important to note that individual responses to these supplements may vary.
Caveats:
We need cholesterol, so in the interest of the baby, Statins should be prescribed only with care.
Drugs such as Finasteride can block Allopregnanolone production, 100% and are to be avoided.
In “true” hypothyroidism, T4 works well. But In stress-related hypothyroidism, it makes things worse.
In stress-related hypothyroidism, stress relief is helpful, but the appropriate prescription is T3.
DHEA deficiency should be corrected before conception, but Rx may begin upon diagnosis of pregnancy.
Bioidentical Progesterone is available, legally prescribed (as a spherical, 100 mg tablet). It is almost completely side effect – free, amazingly inexpensive and guaranteed to be converted into Allopregnanolone.
PEA (Palmitoyl Ethanol Amide), also easily available, inexpensive and side effect-free, generates Allopregnanolone so effectively that it is recommended in the treatment of fibromyalgia, the neuropathies and chronic pain syndromes.
A POSSIBLE SOLUTION
Here is a tempting idea:
– Order tests for DHEA, Testosterone, Estradiol, Progesterone, morning Cortisol and the T3/rT3 ratio, along with the diagnostic and “checkup” tests, either before conception or during the consultation visit for diagnosis of pregnancy. This will provide a baseline evaluation, which will facilitate correction of any significant hormone imbalance, should that become necessary.
– Repeat this “hormonal profile” after the first and second trimesters, to ensure that all is well.
– Test each mother on the day of childbirth and 2 days later, to observe her hormone balance. **
– Interview each new mother, with her test results, in the presence of an experienced psychotherapist, 4–7 days after childbirth: if abnormalities are found, and/or if depressive symptoms have begun, restore all hormones, including DHEA, progesterone and thyroid hormones, to normal levels, with oral supplements.***
– Avoid the prescription of synthetic, psychotropic drugs, which might produce untoward effects on the mother’s delicate and unpredictable psychology.
– Repeat the blood studies, 4–7 days later, with a view to adjusting the doses of hormonal supplements.
This protocol should suffice for the diagnosis and economical treatment of many PPD sufferers: a prescription for Zurzuvae can be made, if hormone restoration fails to solve the problem.
Flags
* Medscape Medical News: Air Pollution Tied to Postpartum Depression, October 20, 2023, https://www.medscape.com/viewarticle/997575
**To date, no test for Allopregnanolone is freely available.
*** Allopregnanolone is produced reliably, from progesterone; but a high dose of progesterone may be necessary. The standard dosage is between 100 and 300 mg, but there are no adverse effects from progesterone, so larger doses can be considered.
References
[1] Davis EP, Sandman CA. The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Dev. 2010 Jan-Feb;81(1):131-48. doi: 10.1111/j.1467-8624.2009.01385.x. PMID: 20331658; PMCID: PMC2846100.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846100/#R63
[2] Beitins IZ, Bayard F, Ances IG, Kowarski A, Migeon CJ. The metabolic clearance rate, blood production, interconversion and transplacental passage of cortisol and cortisone in pregnancy near term. Pediatr Res. 1973 May;7(5):509-19. doi: 10.1203/00006450-197305000-00004. PMID: 4704743.
https://pubmed.ncbi.nlm.nih.gov/4704743/
[3] Roti E, Robuschi G, Emanuele R, Benassi L, Bandini P, Russo A, Gnudi A. Concentrazioni di tiroxina, triiodotironina, reverse T3, tireotropo e tireoglobulina nel sangue del cordone ed in quello materno [Concentrations of thyroxine, triiodothyronine, reverse T3, thyrotropin and thyroglobulin in umbilical-cord and maternal blood]. Minerva Pediatr. 1981 Sep 15;33(17):843-6. Italian. PMID: 7311947.
https://pubmed.ncbi.nlm.nih.gov/7311947/
[4] Burman KD, Read J, Dimond RC, Strum D, Wright FD, Patow W, Earll JM, Wartofsky L. Measurement of 3,3′,5′-Triiodothyroinine (reverse T3), 3,3′-L-diiodothyronine, T3 and T4 in human amniotic fluid and in cord and maternal serum. J Clin Endocrinol Metab. 1976 Dec;43(6):1351-9. doi: 10.1210/jcem-43-6-1351. PMID: 826545.https://www.sciencedirect.com/science/article/pii/S2213398422001452#:~:text=Worldwide%2C%20postpartum%20depression%20has%20been,10%E2%80%9320%25%20of%20mothers.&text=The%20prevalence%20of%20PPD%20in,middle%20and%20high%20income%20countries
