Any ideas?

[chronos]

I’ve posted in this forum because I’m sure it’s something to do with hormones, so please accept my apology if it’s a little TMI.

Approximately every two weeks I enter into a 4-5 day period where I suffer extreme fogginess, have trouble getting to sleep and just feel wired. This is accompanied with breakthrough bleeding.

My current meds for the treatment of autoimmune hypopituitarism are listed below. I also have high titers of hashis antibodies. The florinef was added after renin levels tested elevated along with low aldosterone. Adrenal cortex antibodies were negative.

Obviously, the occurrence of breakthrough bleeding began with sex hormone replacement. While I know it is better to cycle sex hormones, it causes unbearable problems for me. Namely, I get the symptoms listed above (and some) and it takes a far longer time for things to get back on line. Notably, changing over from bioidentical progesterone to dydrogesterone has reduced the amount of bleeding, but hasn’t substantially reduced the other symptoms.

I currently take:
pred/HC combo (3.5mg / 8mg) – cortisol equiv 22mg,
natural thyroid extract (90mg) – armour equiv 1.5 grns
thyroxine (50mg)
florinef (0.1mg)
DHEA (20mg)
climara patch (7.6mg)
duphaston (5mg)
testosterone (0.5% x 0.8ml)
HGH (0.33mg)

This is something I’ve been battling for a long time. While the above hormone replacement has dramatically changed my life – i.e. I don’t feel like I’m going to drop dead 😀 – this problem is preventing me from functioning maximally.

Any input would be greatly appreciated.

Thanks.

[DrMariano2]

It is difficult to determine what is occurring just from the medications used without having corresponding labs to determine the effect.

The following labs are some I use:

Free T4, TSH,
Free T3,
Total T3,
Total T4,
Cortisol AM, DHEA-s,
Pregnenolone, Progesterone,
Total Testosterone, Ultrasensitive Estradiol,
Hemoglobin A1c, Fasting Insulin,
IGF-1,
Prolactin,
Comprehensive Metabolic Panel, CBC, Lipid Panel,
Urinalysis,
Ferritin, Magnesium, Random Urine Iodine, Zinc,
Vitamin A (total retinol),
Vitamin D 25-hydroxy,
Vitamin B12, Folate,
Methylmalonic acid urine,
Homocysteine,
Fractionated Plasma Catecholamines,
Random Urine 5-HIAA.

This, coupled with information from the history and physical exam (including left axillary temperature, blood pressure, pulse, weight, height), makes it easier to determine what is occurring.

—

Breakthrough bleeding may be a matter of the Progesterone to Estradiol ratio. Progesterone prevents growth of the endometrial lining, estrogen promotes growth.

Cycling in mood, mental function, or condition often follows adrenal function.

In the follicular phase of the menstrual period, most of the progesterone is produced by the adrenal glands. If adrenal output is compromised, then the lower progesterone cannot counteract estrogen, and menstrual bleeding is heavier or breakthrough bleeding may occur as the endometrium becomes too thick under the influence of estrogen alone.

Artificial progesterones – the progestins, such as Duphastone (which was discontinued in 2008 in the U.K.), do not have all of progesteron’s biological activity. This may cause problems since the progestins also block progesterone’s actions.

[chronos]

Thanks for explaining things in detail.

I’m seeing a new anti-aging doctor on Thursday. Hopefully he can help me out with these labs. My inkling is that my adrenals aren’t properly supported; but I couldn’t find anything to suggest that breakthrough bleeding may be associated with this. I’ve been reluctant to increase cortisol support because I’ve been having problems with peripheral vision loss, which might be an indicator of high BS. This morning, and for the first time, my central vision went hazy as well.

Unfortunately, I had to go with the duphaston because I had problems with depression and/or absorption with different forms (ie. topical, sublingual, oral) of bioidentical progesterones. It also reduced the severity of breakthrough bleeding. Unfortunately, we don’t have prometrium in aus.

Thanks again.

[DrMariano2]

@chronos 1067 wrote:

Thanks for explaining things in detail.

I’m seeing a new anti-aging doctor on Thursday. Hopefully he can help me out with these labs. My inkling is that my adrenals aren’t properly supported; but I couldn’t find anything to suggest that breakthrough bleeding may be associated with this. I’ve been reluctant to increase cortisol support because I’ve been having problems with peripheral vision loss, which might be an indicator of high BS. This morning, and for the first time, my central vision went hazy as well.

Unfortunately, I had to go with the duphaston because I had problems with depression and/or absorption with different forms (ie. topical, sublingual, oral) of bioidentical progesterones. It also reduced the severity of breakthrough bleeding. Unfortunately, we don’t have prometrium in aus.

Thanks again.

Prometrium is a capsule containing progesterone in peanut oil.

Generally, oral progesterone is the form I use most often. Transdermal may be used but its absorption will depend on thyroid function.

Oral progesterone may significantly help sleep and reduce anxiety since the liver may convert up to 90% of it into Allopregnenolone – a metabolite of progesterone which acts similarly to a benzodiazepine in improving GABA sensitivity.

Progesterone is useful also as a precursor for most of the signals produced by the adrenal cortex.

Progesterone is unique in being able to work at both the nervous system and adrenal level when it comes to addressing hypothalamic-pituitary-adrenal axis dysregulation. It can for many women, replace treatment with cortisol and DHEA, for example.

—

Sometimes, adding progesterone may cause depression. This is usually because progesterone increase the production of estrogen receptors, making whatever estrogen there is much more potent. This may then reduce thyroid hormone activity, which then causes the brain to compensate via an increase in norepinephrine signaling with loss of dopamine signaling. This generally is a temporary effect as progesterone’s positive effects counterbalance the increase in estrogen signaling.

Thus, when treating excessive uterine bleeding, “estrogen dominance” as John R Lee, M.D. famously called the problem (http://www.johnleemd.com/), or other conditions of low progesterone, I may avoid adding estrogen while first increasing progesterone until adequate progesterone levels are achieved, while compensating for depression by attending to thyroid hormone signaling, and address depression with an antidepressant, at least temporarily. The advantage of doing this is to avoid problems in progesterone signaling caused by using a progestin (for example, this includes the increase in blood clots and heart attacks that may occur when estrogen and progestins are used together). Once an adequate progesterone level is established, but breakthrough bleeding still occurs, and a higher progesterone dose would be deemed to risk problems (such as oversedation, impaired concentration), then a progestin may be added. The progesterone, itself, would help reduce the risk of the progestin. I prefer the combination to the use of a progestin alone, though prefer progesterone alone if it can be raised to adequate levels to counteract estrogen.

Note that progesterone replacement therapy may often negate the need for estrogen replacement since some of the progesterone will end up becoming estrogen.

—

One of my initial ideas in doing treatment is to sequentially optimize the signals, one after the other, based on a hierarchy, where addressing the most important signals first would self-correct problems in subsequent signals, helping reduce complications, side effects, dosage needed, etc. when addressing subsequent problems. This would overall reduce the number of interventions and the doses needed – reducing the cost of treatment.

An example hierarchy of targets is as follows:

• Norepinephrine
• GABA
• Serotonin
• Insulin
• Cortisol
• DHEA
• Pregnenolone
• Thyroid
• Aldosterone
• Progesterone
• Testosterone
• Estradiol / Estrogen
• Dopamine
• Growth Hormone

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