Progesterone & Sleep Apnea

[Magyar]

Looks like there is some evidence that progesterone can be very helpful in treating sleep apnea.

Effects of progesterone on sleep: a possible pharmacological treatment for sleep-breathing disorders? - PubMed - NCBI

Progesterone therapy for sleep apnea syndrome evaluated by occlusion pressure responses to exogenous loading. - PubMed - NCBI

Sleep Apnea Emerging Strategies | Life Extension

Questions:

Any danger of overdose on progesterone?

What is max recommended dosage? Does time of day matter?

Can it be given to children?

Is it synergistic with and/or dependent on any other substance? (eg vitamin D & K)

Best source?

Thanks in advance.

 

[tara]

Any danger of overdose on progesterone?

I think you can avoid acute overdose hazards (over-anaesesia) by taking a rapidly absorbed formulation like the progesterone in vit-E via gums in small doses (eg 10mg). Then as you figure out dose you may take more, but if you wait 10+ minutes between doses you won't be able to knock yourself out.
For less severe issues, read the threads about peoples experience with progesterone and progest-e.

Have you tried straight forward mechanical methods to keep your mouth shut at night to see if it prevents sleep apnoea? Like a chin strap or small piece of light tape? Might sound scary, but I'd recommend trying at least for a short time to see how it feels if you haven't given it a go. Personally, I didn't have sleep apnoea (as far as I know), but I did have breathing issues at night that were worsened by mouth breathing, and improved by retrining to close mouth. Tape felt much more soothing than I expected (and comes off in a second if you need it to).

 

[Magyar]

Have you tried straight forward mechanical methods to keep your mouth shut at night to see if it prevents sleep apnoea?

Hi Tara,

I do, in fact, tape my mouth and it does help my sleep. However, I still have to sleep on my side and cannot sleep on my back. If I sleep on my back, I wake up due to apnea.

Sleeping on my side is not really a good solution as it is bad for posture and gait. It is easy to recognize slide sleepers as their shoulders are rolled forward. :/

 

[tara]

Can it be given to children?

I don't know about giving it to children - I'd be cautious. (I'm not an expert.)

Is it synergistic with and/or dependent on any other substance? (eg vitamin D & K)

Good nutrition. Personally, I made the mistake of taking it on an empty stomach only once. Not sure about this, but possibly may increase sodium excrection, so if vulnerable to low sodium, may need to compensate with more salt?

Best source?

Some here use progesterone products from:
Kenogen (I've used their Progest-E)
Health Natura
Idealabs
I think these 3 can all deliver quickly and in controlled amounts.
AIUI, many other products such as creams can often be low concentration, some have some negative excipients, and may be harder to control delivery - I've heard progesterone can sit in subcutaneous fat and be released later, making dose control harder. That's why I favoured gum delivery.

If you overdose, I think liver may get more efficient at removing progesterone, which could then make subsequent doses less effective.

 

[kitback]

Looks like there is some evidence that progesterone can be very helpful in treating sleep apnea.

I have taken progesterone for years and it never helped my apnea. Increasing my dosage of thiamine, however, eliminated the problem.

 

[aquaman]

I think Peat mentioned sleep apnea and progesterone in one of the most recent Herb Doctor interviews ??

 

[aquaman]

^^ Andrew on the last show said they would talk about it (and link to CO2) but they ended up taking 35 mins of callers and not covering anything else on progesterone :/

 

[Magyar]

I have taken progesterone for years and it never helped my apnea. Increasing my dosage of thiamine, however, eliminated the problem.

How much thiamine? How long did you take until you noticed positive effects?

 

[tara]

I do, in fact, tape my mouth and it does help my sleep. However, I still have to sleep on my side and cannot sleep on my back. If I sleep on my back, I wake up due to apnea.

I read about CO2 and Buteyko method from Rakhimov at normalbreathing dot com. He says sleeping on back promotes hyperventilation, sleeping on side helps prevent it. I sleep on side. I don't have an ideal position for shoulders and neck yet, but I have more ideas to try. I also retrained diaphragmatic breathing with chest strap (belt) quite quickly and easily. I wonder if that could help make it possible to sleep on back without hyperventilating? Also maybe using pillow or sth to ensure chin is sitting in a position that does not encourage the mouth to fall open (as is part of some cultures, I think)? Also, I managed to sleep on my back when I had a baby lying on it. Maybe a weight on the chest could serve a similar function? Got an obliging cat? :) The problem seems to be that it is too easy for the chest to expand too much and too often while lying on the back. Just breainstorming, don't know if these ideas would help you.
Not to discourage other metabolic support, but I think sometimes mechanical support can be useful too.

 

[kitback]

How much thiamine? How long did you take until you noticed positive effects?

300 mg per day did nothing for me. However, when I increased it to 300 mg taken three times a day, I had no more apnea. The effect was pretty much immediate.

 

[Magyar]

I read about CO2 and Buteyko method from Rakhimov at normalbreathing dot com. He says sleeping on back promotes hyperventilation, sleeping on side helps prevent it. I sleep on side. I don't have an ideal position for shoulders and neck yet, but I have more ideas to try. I also retrained diaphragmatic breathing with chest strap (belt) quite quickly and easily.

I mouth-tape which helps quite a bit and I appreciate the suggestion but Rakhimov, while well-intentioned, is dead wrong.

Side sleeping compresses the shoulder girdle and causes all sorts of downstream problems in the muscles of the neck and back. Sadly, there is no 'ideal position' for head/shoulders side-sleeping. I have even tried expensive wedges designed to take the load off of for side-sleeping shoulders like:

MedCline Advanced Positioning Wedge

But wedges just kick the problem down the street. You are now bending at the waist (see pic of the guy above). That's no bueno too.

I'd like to %$!@& "cure" this damn thing.

 

[tara]

I mouth-tape which helps quite a bit and I appreciate the suggestion but Rakhimov, while well-intentioned, is dead wrong.

Side sleeping compresses the shoulder girdle and causes all sorts of downstream problems in the muscles of the neck and back. Sadly, there is no 'ideal position' for head/shoulders side-sleeping. I have even tried expensive wedges designed to take the load off of for side-sleeping shoulders like:

It might not be so straight forward as right or wrong, but of trade offs involving our particular vulnerabilities. I don't think Rakhimov is wrong about everything, and I'm not sure I've seen him contradict you on this good point you make about posture, though I may have missed it?
I expect lying on the back is easier on the spine, but harder for addressing night-time hyperventilation. That's why I was trying to think about other ways to address that while lying on the back - hence the comments on weight and chest strap.
The only few times I recall being able to sleep on my back in without obvious worsened hyperventilation issues has been ether with a weight on my chest or when I've accidentally fallen asleep in tad asana at the end of a yoga class, in which the practice itself has probably had effects countering the hyperventilation.
Do you have your diaphragm moving smoothly so that it is at play rather than your chest muscles at rest when you are awake? Can you tell what is happening with that during sleep?
I'd love to be able to sleep on my back, but being able to sleep at all takes priority at this time.

 

[Magyar]

My point wrt Rakhimov was that not being able to restfully sleep on one's back is a likely a sign of suboptimal health. :/

 

[tara]

My point wrt Rakhimov was that not being able to restfully sleep on one's back is a likely a sign of suboptimal health. :/

You may well be right that it is a sign of suboptimal health. Which describes many of us here. Not sure if this contradicts Rakhimov or not.
But whatever he thinks, I think that from where we are now, it is useful to look for ways to from where we are towards better health, not behave as though we can already do all the the things that people with optimal health can do. Which means for some of us finding ways to interrupt and counteract hyperventilation habits (habits that the people with optimal health don't have) by whatever means are going to work best for us.

 

[tara]

Side sleeping compresses the shoulder girdle and causes all sorts of downstream problems in the muscles of the neck and back. Sadly, there is no 'ideal position' for head/shoulders side-sleeping.

There are some interesting experiences with sleep positions here, but I haven't pursued them much:
Sleep On The Floor

 

[success23]

Sleep Apneas are Increased in Mice Lacking Monoamine Oxidase A

"
Conclusion:
Our results show that MAOA deficiency is associated with increased sleep apnea in mice and suggest that an acute or chronic excess of 5-HT contributes to this phenotype."

 

[Beastmode]

Below is an email I received from Ray last year after asking about progesterone levels and usage for babies at night. The first part is referencing how the mother taking progesterone will be able to transfer it to the baby, however the rest does apply to progesterone and apnea.

"Milk normally contains a significant amout of progesterone. After taking some, it will appear in the milk within a few minutes. The only research with progesterone in babies that I know of related to its use to stimulate breathing, prevent episodes of apnea. During the stress of darkness progesterone tends to fall, so restlessness during that time suggests that there’s not enough progesterone. Although I read articles on the use of progesterone to stimulate breathing about 50 years ago, recent publications seem to think it’s something new."

Adv Exp Med Biol. 2015;860:211-20.
An Overview on the Respiratory Stimulant Effects of Caffeine and Progesterone on
Response to Hypoxia and Apnea Frequency in Developing Rats.
Bairam A(1), Uppari N, Mubayed S, Joseph V.
(1)Pediatric Department, Laval University, Research Center of Centre Hospitalier,
Universitaire de Quebec, Quebec City, QC, Canada, [email protected].
The respiratory stimulant caffeine is the most frequently used xanthine
(theophylline or aminophylline) for the treatment of apnea in premature infants.
It decreases but does not eliminate apnea. In most cases such decreases is
insufficient to prevent the use of artificial ventilation. Progesterone is a
respiratory stimulant in adult mammals including human, and it decreases sleep
apnea in menopausal women. Whether progesterone as an adjunct to caffeine therapy
could be effective in further reducing the frequency of apnea in premature
infants is not known because its respiratory effect in newborns has not been well
studied. Using rat pups at different postnatal ages, we first determined whether
the respiratory stimulant effects of acute caffeine (10 mg/kg, i.p.) or
progesterone (4 mg/kg i.p.) are age dependent. These studies showed that caffeine
enhances the ventilatory response to hypoxia in 1 and 4 days-old rats while it
decreases apnea frequency in 12-days-old. In contrast, progesterone enhances the
ventilatory response to hypoxia in less than 7-days-old but decreases apnea in
1-day-old rats. Preliminary experiments show that administration of progesterone
(4 mg/kg i.p.) to newborn rats that are chronically treated with caffeine
(mimicking its clinical uses - 7.5 mg/kg once/day by gavage) enhances the
respiratory stimulant effects of caffeine. Surprisingly, acute injection of
progesterone enhances apnea frequency and reduces hypoxic ventilatory response in
12-day-old rats.

Exp Physiol. 2014 Nov;99(11):1523-37.
Reduced hypoxic ventilatory response in newborn mice knocked-out for the
progesterone receptor.
Potvin C(1), Rossignol O(1), Uppari N(1), Dallongeville A(1), Bairam A(1), Joseph
V(2).
(1)Department of Pediatrics, CR-CHU de Québec, Université Laval, Québec, Canada.
(2)Department of Pediatrics, CR-CHU de Québec, Université Laval, Québec, Canada
[email protected].
Recent studies showed that progesterone stimulates the hypoxic ventilatory
response and may reduce apnoea frequency in newborn rats, but so far we still do
not know by what mechanisms and whether endogenous progesterone might contribute
to respiratory control in neonates. We therefore determined the role of the
nuclear progesterone receptor (PR; member of the steroid receptor superfamily) by
using wild-type (WT) and PR knock-out (PRKO) mice at postnatal days (P) 1, 4 and
10. We measured the hypoxic ventilatory response (14 and 12% O2, 20 min each) and
apnoea frequency in both male and female mice by using whole-body
plethysmography. In response to hypoxia, WT male mice had a marked hypoxic
ventilatory response at P1 and P10, but not at P4. At P1 and P10, PRKO male mice
had a lower hypoxic ventilatory response than WT males. Wild-type female mice had
a marked hypoxic ventilatory response at P10, but not at P1 and P4. At P1 and
P10, PRKO female mice had a lower hypoxic ventilatory response than WT females.
In basal conditions, apnoea frequency was similar in WT and PRKO mice at P1, P4
and P10. During hypoxia, apnoea frequency was higher in WT male mice compared
with PRKO male mice and WT female mice at P1. We conclude that PR is a key
contributor to the hypoxic ventilatory response in newborn mice, but PR deletion
does not increase the frequency of apnoea during normoxia or hypoxia.
© 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Neurosci Lett. 2014 May 1;567:63-7.
The progestin etonogestrel enhances the respiratory response to metabolic
acidosis in newborn rats. Evidence for a mechanism involving supramedullary
structures.
Loiseau C(1), Osinski D(1), Joubert F(1), Straus C(2), Similowski T(3), Bodineau
L(4).
(1)Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie
Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S
1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris,
France.
(2)Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie
Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S
1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris,
France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service
d'Explorations Fonctionnelles de la Respiration, de l'Exercice et de la Dyspnée,
F-75651 Paris, France.
(3)Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie
Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S
1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris,
France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière Charles Foix, Service de
Pneumologie et Réanimation Médicale, F-75651 Paris, France.
(4)Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1158, Neurophysiologie
Respiratoire Expérimentale et Clinique, F-75005 Paris, France; INSERM, UMR_S
1158, Neurophysiologie Respiratoire Expérimentale et Clinique, F-75005 Paris,
France. Electronic address: [email protected].
Central congenital hypoventilation syndrome is a neuro-respiratory disease
characterized by the dysfunction of the CO2/H(+) chemosensitive neurons of the
retrotrapezoid nucleus/parafacial respiratory group. A recovery of CO2/H(+)
chemosensitivity has been observed in some central congenital hypoventilation
syndrome patients coincidental with contraceptive treatment by a potent
progestin, desogestrel (Straus et al., 2010). The mechanisms of this progestin
effect remain unknown, although structures of medulla oblongata, midbrain or
diencephalon are known to be targets for progesterone. In the present study, on
ex vivo preparations of central nervous system of newborn rats, we show that
acute exposure to etonogestrel (active metabolite of desogestrel) enhanced the
increased respiratory frequency induced by metabolic acidosis via a mechanism
involving supramedullary structures located in pontine, mesencephalic or
diencephalic regions.

Adv Exp Med Biol. 2012;758:43-8.
Dose dependent effect of progesterone on hypoxic ventilatory response in newborn
rats.
Hichri O(1), Laurin JC, Julien CA, Joseph V, Bairam A.
(1)Département de Pédiatrie, Université Laval, Québec, Canada.
The effect of progesterone as a respiratory stimulant in newborn subjects is less
known than that in adults. This study investigated the dose-response curve (0, 2,
4, and 8 mg/kg, ip) of progesterone on ventilation in non-anesthetized newborn
rats at 4- and 12-days old using plethysmography. Progesterone had no effects in
the regulation of normoxic ventilation. However, it enhanced the response to
moderate hypoxia (FiO(2) 12%, 20 min) in 4- but not in 12-days old pups. This
response was similar between the dose of 4 and 8 mg/kg. These observations
suggested that progesterone enhances in age- and dose-dependent manner the
hypoxic ventilatory response in newborn rats.

J Appl Physiol (1985). 1996 Jan;80(1):166-75.
Rebound increase in fetal breathing movements after 24-h prostaglandin E2
infusion in fetal sheep.
Hollingworth SA(1), Jones SA, Adamson SL.
(1)Program in Development and Fetal Health, Mount Sinai Hospital, Toronto,
Canada.
We investigated the hypothesis that the precipitous decrease in prostaglandin E2
(PGE2), a potent inhibitor of fetal breathing, from high plasma concentrations
during labor causes a rebound stimulation of breathing without newborn
concentrations falling below prelabor fetal values. Fetal plasma PGE2
concentration was gradually increased from 384 +/- 82 (SE) pg/ml in 2-h steps [0
(baseline), 1.5, 3, and 6 micrograms/min] to labor levels (1,230 +/- 381 pg/ml at
6 micrograms/min) and then was maintained for 24 h (n = 9). PGE2 at 1.5
micrograms/min significantly decreased breathing incidence [from 42 +/- 4
(baseline) to 14 +/- 4%] and breath amplitude (from 2.1 +/- 0.5 to 1.5 +/- 0.2
arbitrary units) and increased breath-to-breath interval (from 1.16 +/- 0.07 to
1.56 +/- 0.06 s). No further dose-related changes were observed. During the first
2 h after PGE2 infusion was stopped, PGE2 concentration returned to basal (352
+/- 64 pg/ml) but breathing incidence and amplitude were significantly higher (74
+/- 8% and 2.4 +/- 0.3 arbitrary units, respectively) and breath-to-breath
interval was significantly lower (0.95 +/- 0.10 s) than were basal levels.
Changes arose within approximately 15 min and were maintained for at least 4 h.
Breathing did not change significantly in the saline-treated group (n = 7).
Results suggest that the rapid decrease in plasma PGE2 concentration at birth
promotes the onset of breathing.

Respir Physiol Neurobiol. 2007 Apr 16;156(1):9-16.
Progesterone increases hypoxic ventilatory response and reduces apneas in newborn
rats.
Lefter R(1), Morency CE, Joseph V.
(1)Department of Pediatrics, Laval University, Centre de Recherche (D0-711),
Hôpital St.-François d'Assise, 10 rue de l'Espinay, Québec G1L 3L5, Canada.
We hypothesized that progesterone may enhance the hypoxic ventilatory response
and reduce the occurrence of apneas in newborn male rats. We studied 10-day-old
rats chronically exposed to progesterone (Prog) or vehicle through the milk of
lactating mothers. Respiratory and metabolic recordings were performed using
whole body plethysmography under normoxia and during hypoxic exposure (10%
O(2)--30 min). While progesterone did not alter baseline breathing and metabolic
rate, it increased hypoxic ventilatory response particularly by limiting the
magnitude of the ventilatory roll-off during the second phase of the hypoxic
ventilatory response (i.e. following 5 min of exposure). In parallel,
progesterone lowered the number of spontaneous apneas and drastically reduced the
occurrence of post-sigh apneas during hypoxic exposure by limiting the time of
the post-sigh expiratory pause. Following domperidone injection (used to block
peripheral D2 dopamine receptor), minute ventilation increased in Veh pups and
the number of spontaneous apneas decreased. These responses were not observed in
Prog pups, suggesting that progesterone reduces peripheral dopaminergic
inhibition on breathing. We conclude that progesterone is a potent stimulant of
hypoxic ventilatory response in newborn rats and effectively reduces the
occurrence of apneas.

Respir Physiol Neurobiol. 2008 Dec 31;164(3):312-8.
Contrasting effects of estradiol and progesterone on respiratory pattern and
hypoxic ventilatory response in newborn male rats.
Lefter R(1), Doan VD, Joseph V.
(1)Department of Pediatrics, Laval University, Centre de Recherche (D0-711),
Hôpital St-François d'Assise, 10 rue de l'Espinay, Quebec G1L 3L5, Canada.
We tested the hypothesis that postnatal exposure to progesterone or estradiol
exerts distinct effects on respiratory control, apnea frequency, and on hypoxic
ventilatory response (HVR). To this aim, we assessed breathing pattern using
whole body plethysmography in normoxia and during a sustained hypoxic exposure
(10% O(2)-30min) in 10-day-old male rats raised by dams implanted with osmotic
minipumps delivering either estradiol (E(2), 7.0microgday(-1)),
estradiol+progesterone (E(2)+P, 7.0+70microgday(-1)) or vehicle (propylene
glycol) at a regular flow rate throughout postnatal days 1-14. Compared to
vehicle, E(2) and E(2)+P pups had a reduced ventilation, metabolic rate and
rectal temperature. HVR was specifically increased in E(2)+P pups compared to
controls and E(2) pups. On the contrary, both E(2) and E(2)+P pups did not
reduced metabolism as much as controls during hypoxic exposure, and the decrease
in rectal temperature was abolished. Surprisingly, E(2)+P pups showed a dramatic
elevation of sigh frequency, while progesterone (in E(2)+P compared to E(2) and
Veh pups) reduced apnea frequency. These findings are relevant to better
understand the role of placental steroids on respiratory and metabolic control
during early development in rats, and could ultimately contribute to a better
understanding of specific respiratory control disorders in preterm neonates,
which are chronically deprived from placental steroids exposure.

 

[AnnSimpson]

Hi Tara,

I do, in fact, tape my mouth and it does help my sleep. However, I still have to sleep on my side and cannot sleep on my back. If I sleep on my back, I wake up due to apnea.

Sleeping on my side is not really a good solution as it is bad for posture and gait. It is easy to recognize slide sleepers as their shoulders are rolled forward. :/

Hello. How are you doing so far? What do you think about using various pillows like this? Do you find those effective? I have a few memory foam ones filled with neck supporters. Most of them are made for side sleepers.

 

[tara]

If you haven't seen this thread and links, you might find it interesting:

Bump to add this:

Instinctive sleeping and resting postures: an anthropological and zoological approach to treatment of low back and joint pain