Introduction
Increasing gynaecological disease and better diagnosis drive more uterine and adnexal surgery [3,4]. Hormone deficiency after bilateral oophorectomy has substantially more severe consequences than natural menopause [2–4,6]. Post-oophorectomy syndrome develops with varying severity in 60–80% [3,5], involving autonomic-vascular, emotional and metabolic-endocrine changes, particularly lipid and carbohydrate disturbances [2,5,7]. Given the systemic effects of sex hormones, replacement hormone therapy is the most pathogenetically directed correction [3,4,6]. Non-drug treatments are increasingly important; combined with medication, they may reduce doses while potentiating benefit. Hypoxic therapy is promising [1].
To assess periodic hypobaric chamber hypoxia for rehabilitation of perimenopausal women with surgical menopause.
Materials and methods
Ninety-two women with surgically abolished ovarian function after hysterectomy with adnexectomy were examined. After screening for hormone-therapy contraindications, all received daily transdermal Divigel, 17β-oestradiol, Orion Corporation, Finland, 1 mg. Forty-seven in the main group began it together with Ural-1 chamber hypoxia adaptation. Assessment occurred before and one month later, after the course. Kupperman’s modified menopausal index, as modified by E. V. Uvarova, was assessed. FSH, LH, oestradiol, testosterone, TSH, T4 and T3 were measured by electrochemiluminescence on Elecsis-1010, Switzerland. Cholesterol, HDL-C and triglycerides used Cobas Integra 400 Plus, Switzerland; LDL-C was calculated with Friedwald’s 1972 formula.
Twelve-lead ECG used a multichannel Shiller, Switzerland. B- and M-mode echocardiography used Acuson Computed Sonography 128 XP/10n, calculating by Teicholz in M mode left ventricular end-systolic and end-diastolic dimensions and volumes, stroke volume, cardiac output, ejection fraction and systolic anteroposterior fractional shortening. Statistics used Microsoft Excel following medical-research recommendations, with paired Student’s t-test for quantitative means and a critical t corresponding to 95% confidence, p<0.05.
Adaptation used the first domestic medical vacuum installation, the Ural-1 chamber at Orenburg Regional Clinical Hospital No. 2. It was built at Cryogenmash to a medical-engineering specification jointly developed by the USSR Academy’s Institute of General Pathology and Pathophysiology and Orenburg Medical Institute.
The main course comprised twenty-two three-hour sessions at simulated 3,500 m, 460 mmHg, daily except three holidays and two technical days. Initial sessions increased altitude gradually from 1,000 m by 500 m daily to 3,500 m. Ascent and descent rates were 3–5 m/s.
Results and discussion
Mean ages were 47.8±1.2 in the main group and 48.4±1.2 in controls, range 45–54 in both. Surgical menopause lasted one month to two years, mean 0.9±0.04 years, with mean age at surgery 47.6±0.2. Comorbidities were common: cardiovascular disease in nineteen (40.4%) versus twenty-one (46.7%), gastrointestinal disease in twenty-eight (59.6%) versus twenty-four (53.3%), and urinary disease in sixteen (34%) versus thirteen (28.9%).
All ninety-two developed post-oophorectomy syndrome. It began on postoperative days three to five in thirty-two (34.8%), within three months in sixty (65.2%), including the first month in thirty-eight (41.3%). Fifty-two (56.5%) had moderate and forty (43.5%) severe syndrome.
Combined treatment using adaptation to periodic chamber hypoxia produced substantially more pronounced positive changes in the well-being of main-group patients with post-oophorectomy syndrome than in control patients receiving hormone replacement alone. Overall, the mean time until positive changes in patient condition during therapy was 11.4±1.3 days in the main group and 23.7±1.5 days in controls.
By course completion, modified menopausal index scores decreased significantly, both overall and for symptom groups. Baseline neurovegetative scores were 32.6±1.2 in the main group and 30.8±1.4 in controls.
Treatment rapidly reduced pathological symptoms. Hot flushes and sweating decreased in thirty (63.8%) and disappeared in seventeen (36.2%) of the main group. Forty-two (89.4%) reported easier sleep onset and better sleep. Headache and dizziness decreased in 80.9%. Palpitations and varied cardiac pain, initially troubling 95.7%, decreased progressively and improved in 91.5% by completion. Numbness, crawling sensations, cold sensitivity and heat intolerance diminished in 82.9%.
By the end, 95.8% of the main group lost an average 4.2% of body weight.
Hormone replacement combined with hypobaric therapy significantly reduced systolic blood pressure in the examined women by 7%, diastolic blood pressure by 6%, pulse pressure by 9% and heart rate by 3%. In the control group, none of these parameters showed statistically significant differences.
Assessment after treatment showed the modified menopausal index for neurovegetative disturbances falling to 9.8±0.8 points in the main group receiving combined therapy, a 70% reduction from baseline. In controls receiving hormone replacement alone, the neurovegetative index declined to 21.2±1.02 points, only 31% below baseline.
Reduced work capacity, fatigue, tearfulness, depression and reduced or absent libido predominated. Baseline emotional index scores were 17.3±1.23 versus 16.8±1.43. Combined therapy improved emotional state and normalised mood. Complaints of tearfulness decreased in 95.7%, depression in 87.2%, irritability in 93.6% and fatigue in 89.4%. Overall emotional scores fell 63.6%, from 17.3±1.23 to 6.3±0.9, versus only 25%, from 16.8±1.41 to 12.6±1.22, in controls.
Before treatment, follicle-stimulating hormone was 110.9±4.8 IU/mL in the main group and 113.2±4.3 IU/mL in controls (Table 1). Combined treatment with periodic chamber hypoxia adaptation significantly lowered it to 54.9±2.6 IU/mL, a 50% decrease. Controls receiving hormone replacement alone also showed a significant decrease, to 76.3±1.96 IU/mL, or 33%, seventeen percentage points less than in the main group.
Both groups initially had high luteinising hormone levels: 49.9±1.9 IU/mL in the main group and 47.6±1.6 IU/mL in controls. Treatment significantly reduced luteinising hormone in the main group to 26.8±1.2 IU/mL, a 46% decrease, whereas the control-group value fell significantly to 34.2±1.04 IU/mL, only 28%.
Oestradiol assessment initially revealed very low values: 11.9±0.8 pg/mL in the main group and 12.2 pg/mL in controls. Treatment significantly increased concentrations, but the increase following hypoxia adaptation was more pronounced, reaching 53.2±1.16 pg/mL, compared with only 41.2±0.94 pg/mL in controls.
These findings suggest increased oestrogen availability through activated extragonadal synthesis after oophorectomy. Testosterone increased significantly to 0.148±0.006 nmol/L, or 14%, with hypoxic therapy, versus only a 3% change in controls.
After hypoxic adaptation, TSH decreased significantly from 3.9±0.34 to 2.6±0.13 mIU/L, while T3 rose nonsignificantly from 2.3±0.13 to 2.6±0.12 nmol/L and T4 from 107.2±2.7 to 110.4±3.9 nmol/L, suggesting increased thyroid functional activity.
Hypercholesterolaemia occurred in 76.6% of the main group and 82.2% of controls (Table 2). Mean total cholesterol was 6.27±0.11 mmol/L and 6.16±0.09 mmol/L, respectively. After combined treatment including chamber hypoxia, main-group cholesterol decreased significantly by 17% from baseline. In controls receiving hormone replacement alone, it decreased only 6%. Chamber hypoxia produced a significant HDL-cholesterol increase of 13.7% in the main group. LDL-cholesterol, initially above acceptable limits, decreased significantly by 27.6%. Consequently, the atherogenic index fell significantly by 34.2%.
Baseline ECG abnormalities occurred in forty-two (89.4%) of the main group; five (10.6%) had normal ECGs. Nonspecific terminal ventricular-complex changes, flattened or slightly negative T waves and ST depression, occurred in thirty-three (70.2%). Repolarisation abnormalities accompanied cardiac pain in twenty-four (51%). Eighteen (38.3%) had right bundle conduction disturbances, five incomplete right bundle branch block; three (6.4%) short PQ. Sinus bradycardia or tachycardia occurred in six (12.8%); ECG left ventricular hypertrophy in five (10.6%). After hypoxic adaptation, thirty-nine (83%) showed ECG improvement with clinically less frequent and severe cardiac pain.
Baseline echocardiography showed lower-than-age-normal stroke volume, cardiac output, ejection fraction and systolic left ventricular anteroposterior fractional shortening (Table 3).
After periodic chamber hypoxia adaptation, end-diastolic and end-systolic dimensions decreased significantly by 4.4% and 6.9%, respectively. Left ventricular end-diastolic and end-systolic volumes decreased by 12.1% and 5.4%. Treatment significantly increased ejection fraction by 11.4% and systolic anteroposterior fractional shortening by 17.4%. Alongside a 19.2% increase in stroke volume, initially reduced cardiac output rose 30.5%. These findings indicate improved left ventricular myocardial contractility.
Conclusions
Combined therapy with periodic chamber hypoxia reduced neurovegetative and emotional manifestations of post-oophorectomy syndrome and improved quality of life after surgical menopause.
Hormonal changes were more pronounced: FSH, LH and TSH decreased while oestradiol and testosterone increased.
Hypobaric hypoxia produced effects limiting metabolic-endocrine disturbances: lower blood pressure and weight, fewer atherogenic lipid changes and improved left ventricular systolic function.
Including this method within rehabilitation for women with surgical menopause increases treatment effectiveness. It also opens the prospect of using this non-drug approach in patients resistant to hormone replacement, and in women not receiving hormone replacement or with contraindications to it.
Table 2. Blood lipid profile (M±m)
| Parameter | Main: before, n=47 | Main: after | Control: before, n=45 | Control: one month |
|---|---|---|---|---|
| Cholesterol, mmol/L | 6.27±0.11 | 5.2±0.1* | 6.16±0.09 | 5.8±0.01* |
| HDL-C, mmol/L | 1.31±0.04 | 1.49±0.04* | 1.32±0.04 | 1.34±0.03 |
| LDL-C, mmol/L | 4.16±0.14 | 3.01±0.11* | 4.04±0.12 | 3.66±0.12 |
| Triglycerides, mmol/L | 1.7±0.09 | 1.5±0.07* | 1.8±0.09 | 1.76±0.08 |
| Atherogenic index | 3.8±0.18 | 2.5±0.1* | 3.7±0.15 | 3.3±0.18 |
* p<0.05 versus baseline.
References
1. Горанчук В. В. Гипокситерапия/В. В. Горанчук, Н. И. Сапова, А. О. Иванов.— СПб.: ЭлБИ-СПб., 2003.— 536 с.
2. Гормональная реабилитация женщин при выпадении функции яичников: пособие для врачей/В. И. Кулаков, Е. В. Уварова, С. В. Юренева, Г. Р. Байрамова.— М., 2004.— 17 с.
3. Кулаков В. И. Постовариэктомический синдром: клиническая лекция/В. И. Кулаков, С. В. Юренева, Е. Ю. Майчук.— М., 2003.— 20 с.
4. Кулаков В. И. Руководство по климактерию/ В. И. Кулаков, В. П. Сметник.— М.: Медицинское информационное агентство, 2001.— 495 с.
5. хирургическая менопауза: пособие для врачей/Под ред. В. И. Кулакова, В. П. Сметник, С. В. юреневой и др.— М., 2003.— 40 с.
6. Increased cardiovascular mortality after early bilateral oophorectomy/C. M. Rivera, B. R. Grossardt, D. J. Rhodes et al.//Menopause.— 2009.— № 16.— Р. 15—23.
7. Parker W. H. Oophorectomy and cardiovascular mortality: is there a link?/W. H. Parker, J. E. Manson//Maturitas.— 2009.— № 16.— Р. 1—2.
Full main-text translation of: Константинова О.Д., Тиньков А.Н., Кшнясева С.К. Метод адаптации к периодической гипоксии в реабилитации женщин с хирургической менопаузой. Пермский медицинский журнал. 2010;27(3):67–74.
Related resources
Related resources cover technology, equipment and applications.