Most of us picture breathing as something the lungs do, and the reproductive system as something entirely separate. They are not as separate as they look. One hormone sits quietly at the meeting point of the two, shaping how a woman breathes across her whole life, and most women have never been told about it.
That hormone is progesterone.
A reproductive hormone that controls the breath
Progesterone is best known for its role across the menstrual cycle and in pregnancy. Far less known is that it is also a respiratory stimulant. It acts on the breathing centres of the brainstem to increase ventilation, and the effect is strong and long documented. When progesterone is given to people who are not pregnant, breathing increases and sensitivity to carbon dioxide rises[ref1]. The effect is not unique to women. It has been shown in men given the hormone in a laboratory, and in animals. Any body exposed to progesterone breathes a little more.
The difference is that women live with it, month after month, for decades. After ovulation, in the two weeks known as the luteal phase, progesterone climbs and breathing rises with it, and the level of carbon dioxide in the blood drops slightly as a result. In a woman whose breathing is healthy to begin with, the body compensates quietly and there are no symptoms. Studies that measured blood chemistry across the cycle found that as breathing lowered carbon dioxide in the luteal phase, the kidneys adjusted to hold the blood's acid-base balance steady[ref2]. The system is doing exactly what it was built to do.
Not every woman starts with room to spare, though. If her baseline breathing already runs a little high, from stress or a shallow chest pattern, the same monthly drop can push her past the point where she feels it. This is the week when many women notice their mood turn, their sleep fray, and cramps set in, and the timing is not a coincidence. In one small study of women with severe premenstrual symptoms, when researchers used medication to stop progesterone from rising, the usual premenstrual fall in carbon dioxide did not happen, and the symptoms that normally came with it did not appear either[ref3]. Same hormone, same mechanism, playing out every month, decades before menopause is anywhere in view.
The quiet work of steady nights
It helps to think of this as one effect with two faces. Progesterone raises the drive to breathe. By day, as we just saw, that shows up as breathing a little more. At night, that same steady drive, together with better tone in the muscles of the upper airway, is what keeps the breath regular through sleep so that it does not turn shallow or stall between breaths. Researchers have long proposed that this is part of why women in their reproductive years tend to have more stable breathing in sleep than they otherwise would[ref4]. In effect, a hormone has been doing some of the steadying work for them, without their ever noticing it was there.
What changes at menopause
Perimenopause is where the rhythm becomes unpredictable. Progesterone no longer rises and falls on a reliable monthly schedule, and for many women this transition feels more turbulent than the steady cycling years that came before it or the years that follow. As progesterone withdraws, the quiet support it lent to steady breathing withdraws along with it.
This is one reason sleep and a sense of calm can feel different in this stage of life. Researchers have observed that breathing during sleep tends to become less steady after menopause, and that the loss of progesterone's respiratory-stimulant effect appears to be one of the factors involved, alongside the other changes of midlife. In one large population study the prevalence of sleep apnea in postmenopausal women not using hormone replacement was significantly higher than in premenopausal women, and closer to the level seen in men[ref4][ref5]. It is rarely traced back to the breath, because almost no one is looking there.
Why the transition can be the hardest part
It is worth pausing on the transition itself, because for many women it is the hardest stretch, harder even than the years that follow. The menopausal transition is, by a wide margin, when women report the most disturbed sleep, with trouble falling asleep and staying asleep especially common through perimenopause[ref6]. Part of the reason is simple: the body copes far better with a steady hormonal setting than with a moving one, and perimenopause is nothing if not a moving one. Once things settle at a new normal on the far side, many women find some of it eases. For those who arrive there abruptly, through surgery rather than over years, the change can land harder still, because it comes all at once.
There is a second, quieter problem, and it is the one almost no one names. A breathing pattern built over decades does not vanish when the hormone that shaped it leaves. If a woman has spent years breathing a little high and a little fast, from stress, from holding the stomach in, from a lifetime of shallow chest breathing, that pattern has become her default. At night, progesterone was in a sense smoothing it over by keeping the drive to breathe up. When the hormone withdraws, the underlying habit is simply uncovered. The hormone leaves. The habit stays. And now there is nothing softening it.
This is part of why sleep is so often where the change shows up first. As the steadying drive fades, the breath through the night grows lighter and easier to interrupt, sleep becomes more fragile, and a woman can wake less rested than her hours in bed would promise. The daytime cost follows from there, the fog and the shorter fuse and the sense of running on less, and it is rarely put down to breathing, because the breath is the last place anyone thinks to look.
That blind spot is not entirely an accident. For most of the history of medicine, women were left out of the research. In the United States, the National Institutes of Health did not require women to be included in clinical studies until 1993[ref7]. A great deal of what we still call a normal breath, a normal blood gas, a normal response to carbon dioxide, was first measured in men. The question of how a body that moves through decades of hormonal change actually breathes was, for the most part, never systematically asked. We are only beginning to ask it now.
Breathing you can steady on purpose
The hopeful part is simple. When a hormone is no longer doing the steadying for you, breathing becomes one of the few things in this transition you can actually take into your own hands.
The tools are ordinary and available to anyone: slow, low, rhythmic breathing through the nose, an exhale a little longer than the inhale, a mouth kept gently closed at night, and, over time, a patiently built tolerance to carbon dioxide. None of it asks for a prescription or a device. It asks only for attention turned toward how you breathe, and enough practice that steadier breathing becomes the ordinary way rather than the exception.
References
Progesterone administration increase VE in man, but its effects on ventilatory response to hypercapnia and hypoxia have not been well documented. Accordingly, VE, HVR, and HCVR were measured during placebo and MPA administration in 11 normal men. The effect of MPA (20 mg orally q 8 hr for 32 hr) on T degrees, metabolic rate (VO2 and VCO2) was also determined. With MPA, T degrees, rose 0.4 degrees C +/- 0.0008 (S.E.M.) p less than 0.0001), VE increased 0.46 +/- 0.16 L/min (p less than 0.01), and VO2 and VCO2 did not change significantly. HCVR (measured under hyperoxic conditions during rebreathing) increased significantly (P less than 0.01) from 2.9 +/- 0.33 L/min/mm Hg (placebo) to 4.0 +/- 0.29 (MPA). HVR was measured as the shape parameter A, so that when A increased, HVR was augmented. During MPA, HVR increased from A = 132 +/- 19.1 to 179 +/- 20.5 (P less than 0.02). We conclude that 60 mg of MPA daily in normal men increases VE and chemosensitivity as measured by the ventilatory response to hypercapnia and hypoxia.
In accordance with Stewart's physicochemical approach, the three independent determinants of plasma hydrogen ion concentration ([H(+)]) were measured at rest and during exercise in the follicular (FP) and luteal phase (LP) of the human menstrual cycle. Healthy, physically active women with similar physical characteristics were tested during either the FP (n = 14) or LP (n = 14). Arterialized blood samples were obtained at rest and after 5 min of upright cycling at both 70 and 110% of the ventilatory threshold (T(Vent)). Measurements included plasma [H(+)], arterial carbon dioxide tension (Pa(CO(2))), total weak acid ([A(Tot)]) as reflected by total protein, and the strong-ion difference ([SID]). The transition from rest to exercise in both groups resulted in a significant increase in [H(+)] at 70% T(Vent) versus rest and at 110% T(Vent) versus both rest and 70% T(Vent). No significant between-group differences were observed for [H(+)] at rest or in response to exercise. At rest in the LP, [A(Tot)] and Pa(CO(2)) were significantly lower (acts to decrease [H(+)]) compared with the FP. This effect was offset by a reduction in [SID] (acts to increase [H(+)]). After the transition from rest to exercise, significantly lower [A(Tot)] during the LP was again observed. Although the [SID] and Pa(CO(2)) were not significantly different between groups, trends for changes in these two variables were similar to changes in the resting state. In conclusion, mechanisms regulating [H(+)] exhibit phase-related differences to ensure [H(+)] is relatively constant regardless of progesterone-mediated ventilatory changes during the LP.
To determine whether women with premenstrual syndrome (PMS) differ from healthy women in the extent of hyperventilation during the luteal phase of the cycle. Case report. Medical university. Three reproductive-age women with severe symptoms of PMS in whom dramatic decline in end-tidal PCO2 (PETCO2) occurred during the luteal phase of the cycle. Measurements of PETCO2, administration of GnRH agonist triptorelin. PETCO2 was determined daily by sidestream capnometry. The decline in PETCO2 in women with PMS was 12-18 mm Hg, on the average. This was significantly more pronounced than the decline of PETCO2 that was observed in healthy women. With the decline of PETCO2 the symptoms of PMS appeared. Symptoms disappeared at the end of the luteal phase when PETCO2 was increasing again. During treatment with the GnRH agonist, PETCO2 did not decline, and all women were free of symptoms. The symptoms of PMS observed in our patients were associated with a pronounced decline of PETCO2 that occurred during the luteal phase of the cycle. Because the symptoms were similar to symptoms observed in the chronic hyperventilation syndrome it is suggested that some symptoms of PMS may be caused by chronic hyperventilation. It appears that in women with PMS the sensitivity of the respiratory center to CO2 is increased more than normal by P or some other secretory product of the corpus luteum, resulting in pronounced hyperventilation with the associated clinical signs and symptoms of a chronic hyperventilation syndrome.
Background: Sleep apnea syndrome (SAS) is a common condition and a risk factor of cardiovascular and cerebrovascular diseases. The purpose of this pilot study was to investigate the effect of a gestagen (trimegeston) and estradiol hormone combination on perimenopausal and postmenopausal women with SAS.
Methods: Four postmenopausal and one perimenopausal women were studied by polysomnography before and after treatment with hormone replacement therapy (HRT).
Results: The subjects had a mean reduction of the severity of their sleep apnea by 75% measured by apnea/hypopnea index.
Conclusions: HRT might be an alternative in the treatment of SAS.
The prevalence of sleep-disordered breathing has not been well studied in women, especially in terms of the effects of age, body mass index (BMI), and menopause. We evaluated this question using a two-phase random sample from the general population. In Phase I, 12,219 women and 4,364 men ranging in age from 20 to 100 yr were interviewed; and in Phase II, 1,000 women and 741 men of the Phase I subjects were selected for one night of sleep laboratory evaluation. The results of our study indicated that, for clinically defined sleep apnea (apnea/hypopnea index > or = 10 and daytime symptoms), men had a prevalence of 3.9% and women 1.2%, resulting in an overall ratio of sleep apnea for men to women of 3.3:1 (p = 0.0006). The prevalence of sleep apnea was quite low in premenopausal women (0.6%) as well as postmenopausal women with hormone replacement therapy (HRT) (0.5%). Further, in these women the presence of sleep apnea appeared to be associated exclusively with obesity (BMI > or = 32.3 kg/m2). Postmenopausal women without HRT had a prevalence of sleep apnea that was significantly higher than the prevalence in premenopausal women with HRT (2.7 versus 0.6%, p = 0.02) and was more similar to the prevalence in men (3.9%), although it remained significantly less when controlling for age and BMI (p = 0.001). These data combined indicate that menopause is a significant risk factor for sleep apnea in women and that hormone replacement appears to be associated with reduced risk.
The menopausal transition is associated with an increase in insomnia symptoms, especially difficulty staying asleep, which negatively impacts quality of life. Vasomotor symptoms are a key component of sleep disruption. Findings from polysomnographic studies are less consistent in showing disrupted sleep in menopausal transition independent of aging; further prospective studies are needed. Hormone therapy alleviates subjective sleep disturbances, particularly if vasomotor symptoms are present. However, because of contraindications, other options should be considered. Further work is needed to develop preventive and treatment strategies for alleviating sleep disturbances to ensure better health, quality of life, and productivity in midlife women.
Keywords: Climacteric; Depressive symptoms; Menopause; Polysomnography; Sleep architecture; Subjective sleep quality; Vasomotor symptoms.
Copyright © 2018 Elsevier Inc. All rights reserved.
Institute of Medicine (US) Committee on Ethical and Legal Issues Relating to the Inclusion of Women in Clinical Studies; Mastroianni AC, Faden R, Federman D, editors. Washington (DC): National Academies Press (US); 1994.
