The exceptional case of a large extra-uterine, so-called parasitic leiomyoma in a post-menopausal woman with Hashimoto's thyroiditis.

A large tumour mass was detected in a 65-year-old patient during a routine gynaecological examination. This patient had been treated for over 10 years with levothyroxine for Hashimoto's thyroiditis and was also given transdermal oestrogen replacement therapy. Before the operation, detailed imaging by CT scan and MRI was performed. A tumour weighing 1.056 grams and measuring 23x12x7 cm was successfully removed through laparotomy. Histopathology revealed the diagnosis of an extra-uterine, so-called parasitic leiomyoma. Post-surgery recovery was uneventful, but Tibolone treatment was indicated due to disturbing menopausal complaints.

Preconception nutraceutical food supplementation can prevent oxidative and epigenetic DNA alterations induced by ovarian stimulation for IVF and increases pregnancy rates.

BACKGROUND: It is hypothesized that oxidative and epigenetic alterations to DNA induced by ovarian stimulation for in vitro fertilization (IVF) may be associated with an increased risk of diseases and cancer in the offspring and could possibly be attenuated by preconception food supplementation. METHODS: In a prospective randomised open-label trial, 62 patients were randomly assigned to either 30 days of preconception treatment with the nutraceutical Fertility woman ® duo (Nutriphyt, Beernem, Belgium) (group 1), this nutraceutical complemented with selenomethionine (group 2), or folic acid only (group 3). Biochemical and epigenetic effects and pregnancy rates were assessed. RESULTS: In all 3 groups the level of DNA oxidative damage, estimated by the concentration of 8-hydroxy- 2-deoxyguanosine over creatinine in early morning urine, and the concentration of homocysteine in the blood decreased after treatment. In group 2, the degree of methylation of the cancer-associated CpG2 dinucleotide of the human Telomerase Reverse Transcriptase (hTERT) promoter region, assessed by pyrosequence in follicular cells obtained at oocyte pick-up, was 18% lower than that of group 3. The pregnancy rate, including the transfer of fresh and frozen embryos, was significantly higher in group 2 (50%) than in group 3 (6%) with the result in group 1 being intermediate (30%). CONCLUSION: The results suggest that preconception food supplementation using a specific nutraceutical significantly reduces oxidative and epigenetic DNA changes to follicular cells of women treated by IVF, and may optimize gene expression in the oocytes, thus increasing the pregnancy rate per cycle of ovarian stimulation.

News and views in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): The role of co-morbidity and novel treatments.

Though affecting many thousands of patients, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) should be considered an orphan disease, since the cause remains elusive and no treatment is available that can provide complete cure. There is reasonable insight into the pathogenesis of signs and symptoms, and treatments specifically directed to immunological, inflammatory and metabolic processes offer relief to an increasing number of patients. Particular attention is given to the importance of co-morbidity requiring appropriate therapy. Promising results are obtained by treatment with Metformin, or possibly Momordica charantia extract, which will correct insulin resistance, with Meldonium improving the transportation of glucose into the mitochondria, with sodium dichloroacetate activating pyruvate dehydrogenase, and with nutraceutical support reducing oxidative and inflammatory impairment.

A mathematical model predicting the individual outcome of IVF through sperm-analysis: The role of the HaloSpermG2® DNA fragmentation test.

The present paper reports the results of a pragmatic prospective trial in a group of 38 random infertile couples in whom a battery of semen assays were performed before in vitro fertilisation (IVF). Sixteen couples (42.1%) attained ongoing pregnancy. Using logistic regression analysis only the result of the Oxisperm® (P = 0.047) and the HaloSperm G2® for DNA fragmentation (P < 0.0001) were significantly associated with the occurrence of pregnancy, whereas neither the conventional semen characteristics, nor the outcome of multiple other tests were significantly related (P > 0.05). Based on the logistic regression analysis the following formula could be derived: Logit(p) = 6.15-0.407 × (% halotest), whereby (p) is the probability of pregnancy, and % halotest is the proportion of spermatozoa showing DNA fragmentation in the HaloSperm G2® test. Receiver operating characteristic curve analysis revealed an area under the curve (AUC) of 0.83. In 16 out of 38 couples the IVF outcome, either positive or negative, could unequivocally be predicted, while in the remaining cases the probability of pregnancy was significantly related to the result of the formula. These findings confirm the hypothesis that sperm DNA-fragmentation largely determines the success of IVF.

External factors affecting fertility, and how to correct their impact.

Fertility of both men and women has been negatively influenced by external factors and life style in recent decennia. Mechanisms of hormone disruption, oxidative damage, and epigenetic DNA changes play a pivotal role in this process. In Belgium, strict regulations have been imposed to reduce the exposure to xeno-estrogens, which has resulted in a partial recovery of sperm quality. At the other hand, more couples require in vitro fertilisation (IVF) whereby ovarian stimulation may be associated with epigenetic DNA hyper-methylation of follicular cells, and increased risk of carcinogenesis among offspring. In order to reduce the health risks for the offspring it is recommended to optimize the oxidative, epigenetic and metabolic situation of both parents by means of lifestyle adaptation, and the use of appropriate food supplementation before conception and during pregnancy.

RCT to evaluate the influence of adjuvant medical treatment of peritoneal endometriosis on the outcome of IVF.

STUDY QUESTION: Does a 3-month adjuvant hormonal treatment of mild peritoneal endometriosis after laparoscopic surgery influence the outcome of IVF stimulation in terms of number of mature oocytes obtained per cycle? SUMMARY ANSWER: Complementary medical treatment of mild peritoneal endometriosis does not influence the number of oocytes per treatment cycle. WHAT IS KNOWN ALREADY: Endometriosis is a disease known to be related to infertility. However, the influence of superficial endometriosis-and its treatment-is still a matter of debate. STUDY DESIGN, SIZE, DURATION: A prospective controlled, randomized, open label trial was performed between February 2012 and March 2014 and embryological and clinical outcomes were measured. Patients with laparoscopically diagnosed peritoneal endometriosis (n= 120) were treated by laser surgery after which they were sequentially randomized by computer-generated allocation to one of the two groups. The primary outcome of the trial was the number of Metaphase II (MII) oocytes. Sample size was chosen to detect a difference of two MII oocytes with a power of 80%. The control group (Group B) received the classical long protocol IVF stimulation, whereas the research group (Group A) had an additional pituitary suppression, of 3 months using a long-acting GnRH agonist, prior to IVF. PARTICIPANTS/ MATERIALS, SETTING, METHODS: A total of 120 patients were included in the study, 61 of them in the study group and 59 patients in the control group. One patient of the control group was lost to follow up leading to 58 evaluable patients. MAIN RESULTS AND THE ROLE OF CHANCE: There was no difference in terms of the number of MII oocytes obtained per cycle: 8.2 in both groups (difference in MII between A and B: 0.07 [-1.89; 2.04] 95% confidence interval (CI)). Pregnancy rate did not differ, being 39.3% for Group A (24 out of 61 patients) versus 39.7% for Group B (23 out of 58 patients) (95% CI around difference in pregnancy rate between A and B: -0.31% [-17.96%; 17.86%]). However, a significantly (P = 0.025) lower dose of FSH (2561 IU for Group A and 2303 IU for Group B, 95% CI around difference in FSH between B and A: -258.6 IU [-483.4 IU; -33.8 IU]) and a significantly (P = 0.004) shorter stimulation period (Group A 12.3 days and Group B 11.3 days, 95% CI around difference in stimulation period between B and A: -1.03 days [-1.73 days; -0.33 days]) were needed to reach adequate follicle maturation in the control group. LIMITATIONS, REASON FOR CAUTION: The validity of this study is limited to mild peritoneal endometriosis, and does not apply to ovarian endometriosis, which is also commonly seen in infertility patients. WIDER IMPLICATIONS OF THE FINDINGS: There is no indication for complementary medical treatment of peritoneal endometriosis in terms of IVF outcome. On the contrary, stimulation takes longer and requires a higher amount of medication. STUDY FUNDING/COMPETING INTERESTS: There was no external funding for this clinical trial in the IVF Center, AZ Jan Palfijn, Ghent. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: EudraCT nr: 2012-000784-25. TRIAL REGISTRATION DATE: First registration on 29 February 2012 and re-entered on 23 August 2012, NCT01682642 (due to a change of staff). DATE OF FIRST PATIENT'S ENROLLMENT: 8 March 2012.

The andrologist's contribution to a better life for ageing men: part 1.

The present opinion paper, explores the possibility that optimal hormone treatment and judicious nutraceutical food supplement can help ageing men to gain quality-adjusted life years. Testosterone treatment of patients with late-onset hypogonadism is given via the transdermal route or by intramuscular injections. There is overwhelming evidence that testosterone replacement therapy (TRT) has many beneficial effects and increases longevity by approximately 2% per year. On the basis of knowledge of physiology, animal and human experimental data, we explain why TRT reduces the risk of cardiovascular disease and of prostate cancer. However, the total testosterone load supplied per day should remain within the physiological range, and new galenical formulations should be developed, mimicking normal day-night variations.

The andrologist's contribution to a better life for ageing men: part 2.

The long-term intake of a judiciously composed nutriceutical containing low-dose vitamins, antioxidants, minerals and particular herbal preparations seems justified for older persons who take medication, or who consume an unbalanced diet, or who are exposed to environmental toxins. Recent reports suggest these nutriceuticals may delay age-related diseases and the occurrence of cancer, and reduce mortality in apparently healthy ageing men. Food supplementation with a nutriceutical that was formulated particularly for ageing men should result in an increase of at least one quality-adjusted life year and may lower the financial and social burden of disease in elderly people.

Hormone replacement therapy and longevity.

To assess whether hormone replacement therapy influences longevity, an analysis was made of published life tables allowing for the calculation of the relative benefit of hormone replacement therapy on longevity in men with late onset hypogonadism and in post-menopausal women. It was found that testosterone replacement therapy of men suffering from late onset hypogonadism increased survival rate by 9-10% in 5 years, similar to that of eugonadal, non-LOH men with normal endogenous testosterone secretion. Oestrogen replacement therapy resulted in increased survival by 2.6% in 5 years. It is concluded that hormone replacement therapy increases longevity.

Hormones, herbal preparations and nutriceuticals for a better life after the menopause: part I.

In developed countries, women spend more than one-third of their life in the menopause and at least half of them experience vasomotor symptoms that impair their normal function and well-being. Long-term estrogen replacement therapy (HRT) with estrogen can suppress typical menopausal symptoms and prevents osteoporosis. When estrogen-only HRT is started within 10 years after the menopause, the prevalence of cardiovascular disease is reduced, mortality is lower, and the risk of breast cancer is not significantly increased. Postmenopausal genital and urinary problems with recurrent infections, incontinence, and dyspareunia can effectively be treated by vaginal application of estriol, which seems to be safe for women treated for breast cancer. HRT after the age of 60 years is associated with a lower number needed to treat than number needed to harm, implying that there would be one unfavorable side-effect for up to ten women experiencing a positive effect. However, further studies are needed regarding the risk-benefit ratio of HRT in women over 70 years. It is concluded that transdermal substitution therapy with estradiol may increase the number of quality-adjusted life years of postmenopausal women. The combination with nutriceutical food supplementation may add to this benefit, but complementary prospective trials are still needed.

Hormones, herbal preparations and nutriceuticals for a better life after the menopause: part II.

Long-term estrogen replacement therapy with estrogen has benefits for many postmenopausal women. However, some women prefer non-steroidal substitution with herbal preparations. The effectivity against vasomotor symptoms has been evidenced for the extracts of pine bark, of linseed and of Lepidium meyenii (Maca), whereas there is controversy about the effectiveness of genistein-rich soy extract. The extracts of cruciferous vegetables such as Broccoli and of linseed induce changes in the metabolism of estrogens, and antioxidants may reverse altered epigenetic DNA methylation, possibly reducing the risk of breast cancer or its recurrence. Indirect evidence from the literature and from clinical trials supports that a nutriceutical composed of plant extracts, low-dose vitamins and minerals may improve the quality of life by delaying certain age-related diseases. On the basis of epidemiologic studies, physiopathological considerations and controlled prospectieve trials, it is suggested that transdermal substitution therapy with estradiol together with nutriceutical food supplementation may increase the number of quality-adjusted life years of postmenopausal women, but complementary, large-scale, prospective trials are still needed.

The serum estradiol concentration is the main determinant of the estradiol concentration in normal breast tissue.

BACKGROUND: The estrogen concentration has been determined in breast tissue, focusing largely on samples obtained from breast cancers. In this study, estradiol concentration was determined in normal breast tissue obtained from women undergoing esthetic, and oncoplastic surgery. METHODS: Normal breast tissue was obtained during 68 operations for esthetic or reconstructive indications in women with and without a history of breast cancer. Our study included six different groups of women. The first three groups were normal cycling women, women taking oral contraceptives, and normal postmenopausal women, all undergoing a bilateral esthetic breast reduction. The second three groups were premenopausal and postmenopausal women, with a history of breast cancer and currently taking tamoxifen treatment, or postmenopausal women currently taking an aromatase inhibitor, needing contra-lateral corrective esthetic surgery. FINDINGS: In the group of women without history of breast cancer, normal cycling women (n=24) presented a strong correlation (r=0.853; P<0.0001) between 17ß-estradiol concentration in serum (median: 29.7 pg/mL; IQR: 10.8-82.3 pg/mL) and in breast tissue (30.6 pg/g; IQR: 18.6-183.8 pg/g). Postmenopausal women had low 17ß-estradiol concentrations both in serum and breast tissue (r=0.813; P<0.0001, n=16). Women taking oral contraceptives (n=12) had low serum and breast tissue levels of estradiol (r=0.376; P=n.s.). Premenopausal women (n=6, mean age: 44.2 years) with a history of breast cancer and currently taking tamoxifen, had very high concentrations of 17ß-estradiol both in serum (277.9 pg/mL; IQR: 96.2-544.7 pg/mL) and in epithelial cells (251.9 pg/g; IQR: 115.0-426.5 pg/g) (r=0.803; P<0.001). Postmenopausal women taking tamoxifen (n=4, mean age: 48.3) had low concentrations of 17ß-estradiol in serum (7.0 pg/mL; IQR: 5.7-16.3 pg/mL) and in epithelial cells (14.6 pg/g IQR: 13.3-16.3 pg/g) (r=0.10; P=n.s.). The estradiol concentration in the breast of premenopausal women taking tamoxifen was 8.2 times higher that observed in the breast of normal cycling women, and 17.3 times higher that observed in postmenopausal women taking tamoxifen. Women taking adjuvant aromatase inhibitors had extremely low concentrations of 17ß-estradiol both in serum and in breast tissue. INTERPRETATION: This study shows that serum estradiol levels largely determine estrogen levels in normal breast tissue.

Comparing the effectiveness of infertility treatments by numbers needed to treat (NNT).

To compare the clinical efficiency of different modes of treatment of infertile couples and to estimate the possible benefit of nutraceutical food supplementation (NFS), the numbers needed to treat (NNT) was calculated in 4143 infertile couples based on controlled trials in recent literature and personal data. The NNT expresses the number of individuals who need to be treated to obtain one complementary pregnancy. In female infertility, the NNT of mild or moderate endometriosis was 8.4, and in anti-estrogens treatment of anovulation, it was 5.9. In tamoxifen treatment of idiopathic oligozoospermia, NNT was 3.9, and in antioxidant supplementation, it was 7.8. Treatment of varicocele yielded NNT of 6.3 and 6.8 after 1 year in multi- or single-centre trials, respectively, and NFS lowered the NNT after 3 months to 2.6. Adding NFS to the male partner increased the ongoing pregnancy rate by IVF with NNT of 8.3, and adding NFS to both partners reduced the NNT to 4.0. Although these results were obtained in heterogeneous trials and populations, it is suggested that the NNT should be useful for comparing the effectiveness of different modes of treatment of the infertile couple, and that complementary nutraceutical food supplementation may be beneficial.

Canine hip dyslasia: the significance of the Norberg angle for healthy breeding.

OBJECTIVES: To assess the reproducibility of the Fédération Cynologique Internationale (FCI) classification over time, and between assessors and to evaluate the benefit of computer-assisted measurement of the Norberg angle and of its percentile ranking by breed for the diagnosis of canine hip dysplasia, and for the selection of couples for breeding. METHODS: During the time period of 2006 to 2010, 5094 hip radiographs were evaluated according to the FCI rules, and 4400 have been submitted for statistical analysis. A system of computer-assisted image analysis (Digimizer(®) , MedCalc Software Ltd, Mariakerke, Belgium) was used to measure the Norberg angle. The Norberg angle value of individual dogs was expressed as percentile rank by breed. RESULTS: The agreement between individual assessors was highly significant (P<0·001), but there were important variations over time of the ratio of classes A or B. The Norberg angle and the percentile rank accurately discriminated between dogs with or without canine hip dysplasia, with positive and negative likelihood ratios of 6·31 and 0·21, respectively, for the Norberg angle at criterion value of 102·2°, and 4·21 and 0·18 for the percentile rank at criterion value of the 25th percentile. CLINICAL SIGNIFICANCE: The percentile rank of the Norberg angle may be a valuable tool for breeding selection.

Cholesterol and desmosterol in two sperm populations separated on Sil-Select gradient.

Sperm lipids are important for sperm viability, maturity and function. This study aimed to identify cholesterol and desmosterol composition of human spermatozoa of two sperm populations separated on Sil-Select gradient. Forty-eight males were divided into four groups namely healthy men (n = 13), asthenozoospermia (n = 11), asthenoteratozoospermia (n = 10) and oligoasthenoteratozoospermia (n = 14). Sperm cholesterol and desmosterol were estimated in two human sperm population separated by centrifugation in a discontinuous Sil-Select gradient. The results showed that cholesterol and desmosterol were the major sterols in human spermatozoa. Spermatozoa recovered from upper/lower layer interface (fraction I) had low fertilization potential, while those from the base (fraction II) had high fertilization potential. Median values of cholesterol and desmosterol in fraction I were 2.55 micromol and 0.77 micromol/10(9) spermatozoa and in fraction II were 1.16 micromol and 0.27 micromol/10(9) spermatozoa. Cholesterol/desmosterol ratio was significantly higher in fraction II than I (4.8 vs. 3.2, p < 0.01). Cholesterol, desmosterol, total phospholipids and sterols/phospholipids were negatively correlated with sperm concentrations, sperm motility, linear velocity, normal sperm morphology and acrosome reaction percentage whereas cholesterol/desmosterol ratio was positively correlated with these parameters. It is concluded that the difference in sterol composition of sperm subpopulations separated on Sil-Select gradient suggests that composition of sterols is related to sperm functions.

Anti-proliferative properties of prenylated flavonoids from hops (Humulus lupulus L.) in human prostate cancer cell lines.

Chalcones xanthohumol (X) and desmethylxanthohumol (DMX), present in hops (Humulus lupulus L.), and the corresponding flavanones isoxanthohumol (IX, from X), 8-prenylnaringenin (8-PN, from DMX), and 6-prenylnaringenin (6-PN, from DMX), have been examined in vitro for their anti-proliferative activity on human prostate cancer cells PC-3 and DU145. X proved to be the most active compound in inhibiting the growth of the cell lines with IC50 values of 12.3+/-1.1 microM for DU145 and 13.2+/-1.1 microM for PC-3. 6-PN was the second most active growth inhibitor, particularly in PC-3 cells (IC50 of 18.4+/-1.2 microM). 8-PN, a highly potent phytoestrogen, exhibited pronounced anti-proliferative effects on PC-3 and DU145 (IC50 of 33.5+/-1.0 and 43.1+/-1.2 microM, respectively), and IX gave comparable activities (IC50 of 45.2+/-1.1 microM for PC-3 and 47.4+/-1.1 microM for DU145). DMX was the least active compound. It was evidenced for the first time that this family of prenylated flavonoids from hops effectively inhibits proliferation of prostate cancer cells in vitro.

Combined conventional/antioxidant "Astaxanthin" treatment for male infertility: a double blind, randomized trial.

AIM: To evaluate the treatment of male infertility with a strong natural antioxidant, in addition to conventional treatment. METHODS: Using a double blind, randomized trial design, 30 men with infertility of > or =2 months and female partners with no demonstrable cause of infertility received conventional treatment according to the guidelines of the World Health Organization (WHO), and either a strong antioxidant Astaxanthin 16 mg/day (AstaCarox, AstaReal AB, Gustavsberg, Sweden) or placebo for 3 months. The effects of treatment on semen parameters, reactive oxygen species (ROS), zona-free hamster oocyte test, serum hormones including testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and Inhibin B, and spontaneous or intrauterine insemination (IUI)-induced pregnancies were evaluated. RESULTS: ROS and Inhibin B decreased significantly and sperm linear velocity increased in the Astaxanthin group (n = 11), but not in the placebo group (n = 19). The results of the zona-free hamster oocyte test tended to improve in the Astaxanthin group in contrast with the placebo group, though not reaching statistical significance. The total and per cycle pregnancy rates among the placebo cases (10.5 % and 3.6 %) were lower compared with 54.5 % and 23.1 % respectively in the Astaxanthin group (P = 0.028; P = 0.036). CONCLUSION: Although the present study suggests a positive effect of Astaxanthin on sperm parameters and fertility, the results need to be confirmed in a larger trial before recommending Astaxanthin for the complementary treatment of infertile men.

Is inhibin B involved in the toxic effect of lead on male reproduction?

Human studies indicate exposure to lead is associated with decreased sperm quality with modest, if any, effects on conventional reproductive endocrine profile. Inhibin B is a marker of Sertoli cell function and spermatogenesis. The present study evaluates possible effects of lead exposure on serum levels of inhibin B in a group of lead workers as compared with a non-exposed group of hospital personnel. The study population included 68 healthy Belgian workers from a lead smelter (Hoboken, Belgium) and for comparison a control group of 91 hospital personnel (University Hospital Ghent, Belgium). Semen analysis and measurement of current blood lead levels and serum levels of inhibin B, follicle stimulating hormone (FSH) and estradiol (E2). Lead workers had significantly lower sperm concentration (35 vs. 51 million/mL) and higher serum inhibin B (259 vs. 177 pg/mL) as well as lead blood levels 30.9 vs. 3.4 mug/dL) compared with the hospital personnel (all p < 0.05). Serum FSH and E2 levels were similar in both groups. Overall, inhibin B levels correlated significantly positively with blood lead levels and sperm concentration while it was negatively correlated with serum FSH. In multiple regression analysis of data from all participants, blood lead and serum FSH (p < 0.0001 for both) followed by sperm count (p = 0.007) were selected as the only independent variables for inhibin B with an R-adjusted coefficient of determination of 0.3714. The results of the present study suggest that the exposure of the cells of Sertoli to excessive amounts of lead results in inappropriate inhibin B overproduction that may be involved in the impairment of spermatogenesis.

Preventing diseases of the prostate in the elderly using hormones and nutriceuticals.

The prostate has only one function, namely to secrete fluid containing substances that are needed for reproduction. This requires an extremely high concentration of androgens in the tissues. Benign prostatic hypertrophy (BPH) seems to be related to the long-term exposure of the prostate to the strong androgen 5alpha-dihydrotestosterone (DHT) and, possibly, to estrogens. The relation between prostate cancer and androgens is suggested to be U-shaped, with both extremes of androgen concentrations being associated with increased risk of invasive cancer. In the treatment of patients with BPH, the lipidic liposterolic extracts of Serenoa repens were as effective as the pharmaceutical inhibitors of the 5alpha-reductase enzyme or alpha1-adrenergic blockers in relieving urinary symptoms. In addition to moderately inhibiting the 5alpha-reductase activity, Serenoa seems to exert anti-inflammatory and complementary cellular actions with beneficial effects on the prostate. Unlike the pharmaceutical 5alpha-reductase inhibitors, finasteride and dutasteride, Serenoa does not suppress serum PSA, facilitating the follow-up and the early detection of prostate cancer. We suggest a strategy to prevent prostate cancer that aims at providing men with partial androgen deficiency correct testosterone substitution with a sustained release buccal bio-adhesive tablet. In addition, food supplementation with extracts of Serenoa repens and a combination of the antioxidants selenium, (cis)-lycopene and natural vitamin E, together with fish oil rich in long-chain polyunsaturated essential fatty acids of the omega-3 group seems warranted. Clearly, a holistic approach including careful clinical and biological monitoring of the aging man and his prostate remains mandatory.