Bo von Schoultz

Back Pain During Pregnancy: A Prospective Study

Study Design A longitudinal, prospective, observational, cohort study. Objectives To describe the natural history of back pain occurring during pregnancy and immediately after delivery. Summary of Background Data Back pain during pregnancy is a frequent clinical problem even during the early stages of pregnancy. The cause is unclear. Methods A cohort of 200 consecutive women attending an antenatal clinic were followed throughout pregnancy with repeated measurements of back pain and possible determinants by questionnaires and physical examinations. Results Seventy‐six percent reported back pain at some time during pregnancy. Sixty‐one percent reported onset during the present pregnancy. In this group, the prevalence rate increased to 48% until the 24th week and then remained stable and declined to 9.4% after delivery. The reported pain intensity increased by pain duration. The pain score correlated closely to self‐rated disability and days of sickness benefit. Conclusions Back pain during pregnancy is a common complaint. The 30% with the highest pain score reported great difficulties with normal activities. The back pain started early in pregnancy and increased over time. Young women had more pain than older women. Back pain starting during pregnancy may be a special entity and may have another origin than back pain not related to pregnancy.

Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial.

BACKGROUND Vasomotor symptoms and bone loss are complications frequently induced by adjuvant treatment for breast cancer. Tibolone prevents both side-effects, but its effect on cancer recurrence is unknown. The aim of this study was to show non-inferiority of tibolone to placebo regarding risk of recurrence in breast-cancer patients with climacteric complaints. METHODS Between July 11, 2002, and Dec 20, 2004, women surgically treated for a histologically confirmed breast cancer (T(1-3)N(0-2)M(0)) with vasomotor symptoms were randomly assigned to either tibolone 2.5 mg daily or placebo at 245 centres in 31 countries. Randomisation was done by use of a centralised interactive voice response system, stratified by centre, with a block size of four. The primary endpoint was breast-cancer recurrence, including contralateral breast cancer, and was analysed in the intention-to-treat (ITT) and per-protocol populations; the margin for non-inferiority was set as a hazard ratio of 1.278. This study is registered with ClinicalTrials.gov, number NCT00408863. FINDINGS Of the 3148 women randomised, 3098 were included in the ITT analysis (1556 in the tibolone group and 1542 in the placebo group). Mean age at randomisation was 52.7 years (SD 7.3) and mean time since surgery was 2.1 years (SD 1.3). 1792 of 3098 (58%) women were node positive and 2185 of 3098 (71%) were oestrogen-receptor positive. At study entry, 2068 of 3098 (67%) women used tamoxifen and 202 of 3098 (6.5%) women used aromatase inhibitors. The mean daily number of hot flushes was 6.4 (SD 5.1). After a median follow-up of 3.1 years (range 0.01-4.99), 237 of 1556 (15.2%) women on tibolone had a cancer recurrence, compared with 165 of 1542 (10.7%) on placebo (HR 1.40 [95% CI 1.14-1.70]; p=0.001). Results in the per-protocol population were similar (209 of 1254 [16.7%] women in the tibolone group had a recurrence vs 138 of 1213 [11.4%] women in the placebo group; HR 1.44 [95% CI 1.16-1.79]; p=0.0009). Tibolone was not different from placebo with regard to other safety outcomes, such as mortality (72 patients vs 63 patients, respectively), cardiovascular events (14 vs 10, respectively), or gynaecological cancers (10 vs 10, respectively). Vasomotor symptoms and bone-mineral density improved significantly with tibolone, compared with placebo. INTERPRETATION Tibolone increases the risk of recurrence in breast cancer patients, while relieving vasomotor symptoms and preventing bone loss. FUNDING Schering-Plough (formerly NV Organon, Oss, Netherlands).

CYCLICAL MOOD CHANGES AS IN THE PREMENSTRUAL TENSION SYNDROME DURING SEQUENTIAL ESTROGEN-PROGESTAGEN POSTMENOPAUSAL REPLACEMENT THERAPY

Abstract. The etiology of the cyclical mood changes seen in the premenstrual syndrome is still unknown. A close relation to the luteal phase has been shown. One of the differences between the follicular and the luteal phase is the higher plasma progesterone concentration during the luteal phase. The present investigation has been conducted to study the effect of exogenously administered estrogen/gestagen sequential postmenopausal replacement therapy on mood and physical signs.

Mammographic breast density during hormone replacement therapy: differences according to treatment.

OBJECTIVE Our purpose was to investigate the effects of various hormone replacement regimens on mammographic breast density. STUDY DESIGN Mammographic density was recorded in women participating in a population-based screening program. All women were nonusers of hormone replacement therapy at first mammogram and thereafter reported continuous use of the same treatment: estrogen alone (n = 50) or estrogen in cyclic (n = 75) or continuous (n = 50) combination with progestogen. Mammographic density was quantified according to the Wolfe classification. RESULTS An increase in mammographic density was much more common among women receiving continuous combination hormone replacement therapy (52%) than among those receiving cyclic (13%) and estrogen-only (18%) treatment. The increase in density was apparent already at first visit after the start of hormone replacement therapy. There was little change in mammographic status during long-term follow-up. CONCLUSION Regimens of hormone replacement therapy were shown to have different effects on the normal breast. There is an urgent need to clarify the biologic nature and significance of a change in mammographic density during treatment and, in particular, its relation to symptoms and breast cancer risk.

On the regulation of sex-hormone-binding globulin—A challenge of an old dogma and outlines of an alternative mechanism

In this review, the different factors known to affect SHBG levels are discussed with respect to their possible significance in the physiological regulation of this protein: Sex steroids, puberty, nutritional status, thyroid hormones and liver disease. It is concluded that the serum levels of SHBG are related to general metabolic factors, nutritional status, growth and ageing than to the estrogen/androgen balance. The authors suggest that SHBG is regulated primarily by growth hormone, somatomedin-C and possibly other growth factors. Growth hormone may promote SHBG synthesis in the liver while somatomedin-C may stimulate its extravasation and uptake in target tissues. It is suggested that sex steroids merely have an indirect, modulating influence.

Effects of hormone replacement therapy on the mammary gland of surgically postmenopausal cynomolgus macaques

OBJECTIVE Our purpose was to define the proliferative response and receptor status in the mammary glands of surgically postmenopausal macaques given hormone replacement therapy, equivalent for monkeys to that given women. STUDY DESIGN Surgically postmenopausal adult female cynomolgus macaques (Macaca fascicularis) were given either no treatment (n = 26), conjugated equine estrogens (n = 22), or combined therapy with conjugated equine estrogens and medroxyprogesterone acetate (n = 21). Drugs were administered in the diet, at doses equivalent on a caloric basis to 0.625 mg per woman per day for conjugated equine estrogens and 2.5 mg per woman per day for medroxyprogesterone acetate, for 30 months. Mammary gland proliferation was assessed subjectively and by morphometric and stereologic means. Estrogen receptor and progesterone receptor content and proliferation were studied by immunohistochemistry. RESULTS In this model combined therapy with conjugated equine estrogens and medroxyprogesterone acetate induced greater proliferation than did conjugated equine estrogens alone. The percentage of estrogen receptor-positive cells was decreased in the conjugated equine estrogens plus medroxyprogesterone acetate group. The percentage of progesterone receptor-positive cells was increased by treatment with conjugated equine estrogens alone. CONCLUSION These results indicate a proliferative response of mammary gland epithelium to therapy with conjugated equine estrogens plus medroxyprogesterone acetate in postmenopausal macaques. The clinical implication of this finding may be a greater risk for development of breast neoplasms in women receiving combined hormone replacement therapy.

Serum relaxin, symphyseal pain, and back pain during pregnancy

OBJECTIVE Our purpose was to study the relationship between serum relaxin levels and back pain during pregnancy. STUDY DESIGN A prospective clinical cohort study with repeated examinations was performed. RESULTS There was an initial increase of relaxin levels until a peak value at the twelfth week followed by a decline until the seventeenth week. Thereafter stable serum levels around 50% of the peak value were recorded. Three months after delivery serum relaxin was not detectable. There was a significant correlation between mean serum relaxin levels during the pregnancy and symphyseal pain or low back pain occurring during late pregnancy as measured by medical history or pain-provoking test. CONCLUSION Relaxin is known to remodel pelvic connective tissue in several mammalian species during pregnancy. The current data suggest that relaxin might be involved in the development of pelvic pain in pregnant women.

A randomized trial of the effect of estrogen and testosterone on economic behavior

Existing correlative evidence suggests that sex hormones may affect economic behavior such as risk taking and reciprocal fairness. To test this hypothesis we conducted a double-blind randomized study. Two-hundred healthy postmenopausal women aged 50–65 years were randomly allocated to 4 weeks of treatment with estrogen, testosterone, or placebo. At the end of the treatment period, the subjects participated in a series of economic experiments that measure altruism, reciprocal fairness, trust, trustworthiness, and risk attitudes. There was no significant effect of estrogen or testosterone on any of the studied behaviors.

Growth hormone 24‐h serum profiles during pregnancy—lack of pulsatility for the secretion of the placental variant

Summary. Serum profiles of growth hormone (GW) were recorded for 24 h in women at different stages of normal pregnancy. Two monoclonal antibodies directcd against different epitopes and unaffected by human placental lactogen were used in radioimmunoassays to distinguish the pituitary 22K‐GH from the placental GH variant. The ‘normal’ episodic peak activity of GH in non‐pregnant and first trimester pregnant women was dramatically changed into a continuous very stable secretion during late pregnancy. This change was first observed at 17 weeks gestation. It is concluded that during the second half of pregnancy, serum measurements of GH reflect a major contribution from a non‐cpisodically secreted placental GH variant and a concomitant suppression of pituitary GH. This specific signal, i.e. a continuous GH secretion, may be an important regulator of maternal liver metabolism during pregnancy.

Is sexual life influenced by transdermal estrogen therapy?: A double blind placebo controlled study in postmenopausal women

Two hundred and forty‐two postmenopausal women between 35 and 65 years of age requiring hormone replacement therapy for climacteric symptoms were blindly and randomly allocated to treatment either with transdermal estradiol therapy (Estraderm* 50 μg/24 h) (E) or placebo (P). The patches were changed twice a week and treatment continued for 12 weeks. No progestogen supplement therapy was given during the study. No previous hormone replacement therapy had been given for the last six months and the women had had their last menstruation more than sin months ago. As a part of a larger study assessing womens quality of life, a Swedish version of ‘McCoys Sex Scale Questionnaire’ was administered at the start of treatment and after 12 weeks. This questionnaire contains nine items regarding different aspects of sexual life. The difference between the scorings at the start of treatment and after 12 weeks were calculated for each item and the values of the E and the P groups were compared. Items regarding ‘satisfaction with frequency of sexual activity, sexual fantasies. degree of enjoyment. vaginal lubrication and pain during intercourse’ were positively influenced in the E group compared to the P group. Items not affected were ‘frequency of orgasm and sexual arousal’. A correlation between improved sexual life and quality of life was also found when the results from the McCoy scale were compared with a battery of quality of life questionnaires.