c-Jun NH2-terminal kinase inhibitor bentamapimod reduces induced endometriosis in baboons: an assessor-blind placebo-controlled randomized study.

OBJECTIVE: To test the hypothesis that the c-Jun NH2-terminal kinase (JNK) inhibitor (JNKI) bentamapimod (AS602801/PGL5001) can reduce induced endometriosis in baboons. DESIGN: Prospective randomized placebo-controlled study. SETTING: Nonhuman primate research center. ANIMAL(S): Twenty baboons each underwent four laparoscopies. Initial screening laparoscopy (L1) was followed after one rest cycle by an endometriosis-induction laparoscopy (L2). Fifty days after L2, the baboons were randomized just before staging laparoscopy (L3). Treatment lasted for 60 days, followed by a post-treatment staging laparoscopy (L4). INTERVENTION(S): Randomization before a 60-day treatment in four groups: daily placebo (n = 5), daily oral administration of 20 mg/kg JNKI (n = 5), concomitant daily oral administration of 20 mg/kg JNKI and 10 mg medroxyprogesterone acetate (MPA; n = 5), or subcutaneous administration of 3 mg cetrorelix every 3 days (n = 5). MAIN OUTCOME MEASURE(S): Type, surface area and volume of endometriotic lesions, and revised American Society for Reproductive Medicine score and stage were recorded during L3 and L4. Menstrual cycle length and serum hormonal concentration were recorded before and after treatment. RESULT(S): Compared with placebo, treatment with JNKI, JNKI + PMA, or cetrorelix resulted in lower total surface area and volume of endometriotic lesions. Remodeling of red active lesions into white lesions was observed more frequently in baboons treated with JNKI + MPA than in baboons treated with JNKI only. Menstrual cycle length and serum hormonal concentration were similar between placebo and JNKI groups. CONCLUSION(S): JNKI alone was as effective as JNKI + MPA or cetrorelix in reducing induced endometriosis in baboons, but without severe side effects or effect on cycle length or serum reproductive hormones.

Proteomics analysis of plasma for early diagnosis of endometriosis.

OBJECTIVE: To test the hypothesis that differential surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein or peptide expression in plasma can be used in infertile women with or without pelvic pain to predict the presence of laparoscopically and histologically confirmed endometriosis, especially in the subpopulation with a normal preoperative gynecologic ultrasound examination. METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis was performed on 254 plasma samples obtained from 89 women without endometriosis and 165 women with endometriosis (histologically confirmed) undergoing laparoscopies for infertility with or without pelvic pain. Data were analyzed using least squares support vector machines and were divided randomly (100 times) into a training data set (70%) and a test data set (30%). RESULTS: Minimal-to-mild endometriosis was best predicted (sensitivity 75%, 95% confidence interval [CI] 63-89; specificity 86%, 95% CI 71-94; positive predictive value 83.6%, negative predictive value 78.3%) using a model based on five peptide and protein peaks (range 4.898-14.698 m/z) in menstrual phase samples. Moderate-to-severe endometriosis was best predicted (sensitivity 98%, 95% CI 84-100; specificity 81%, 95% CI 67-92; positive predictive value 74.4%, negative predictive value 98.6%) using a model based on five other peptide and protein peaks (range 2.189-7.457 m/z) in luteal phase samples. The peak with the highest intensity (2.189 m/z) was identified as a fibrinogen ß-chain peptide. Ultrasonography-negative endometriosis was best predicted (sensitivity 88%, 95% CI 73-100; specificity 84%, 95% CI 71-96) using a model based on five peptide peaks (range 2.058-42.065 m/z) in menstrual phase samples. CONCLUSION: A noninvasive test using proteomic analysis of plasma samples obtained during the menstrual phase enabled the diagnosis of endometriosis undetectable by ultrasonography with high sensitivity and specificity. LEVEL OF EVIDENCE: II.

A high sensitivity assay is more accurate than a classical assay for the measurement of plasma CRP levels in endometriosis.

BACKGROUND: Endometriosis is associated with chronic subclinical inflammation. C-reactive protein (CRP), a marker of inflammation, could serve as a biomarker of endometriosis. We tested the hypothesis that a high sensitivity CRP assay (hsCRP) is more accurate than a classical CRP assay in the detection of subclinical inflammation in plasma of women with endometriosis. METHODS: CRP levels were measured by hsCRP and classical CRP assays in plasma of 204 women with endometriosis and 91 women without endometriosis. Both assays were compared with respect to their value for the diagnosis of endometriosis. RESULTS: The number of plasma samples with detectable CRP was significantly higher (100%) using the hsCRP assay when compared to the classical CRP assay (42.7%) (p < 0.0001). Significantly increased CRP plasma levels were found in women with endometriosis when compared with controls when the hsCRP assay was used in samples obtained during the luteal phase (p = 0.008). The highest discriminative ability for the diagnosis of endometriosis was also obtained using the hsCRP assay during the luteal phase, especially for moderate -severe endometriosis. At a cut-off level of hsCRP > 0.71 mg/L, moderate-severe stages were diagnosed with 80.7% sensitivity and 63.9% specificity during the luteal phase. Using a similar cut-off value for CRP analyzed by the classical method, moderate-severe endometriosis was diagnosed with lower sensitivity (67.7%, p = 0.06) and comparable specificity (63.9%). CONCLUSIONS: The hsCRP assay was superior to the classical CRP assay for the detection of low CRP levels and for revealing subclinical inflammation in plasma of women with endometriosis.

How can macroscopically normal peritoneum contribute to the pathogenesis of endometriosis?

This study indicates that the immunobiology of macroscopically normal peritoneum is relevant to understand the pathogenesis of endometriosis. Peritoneal interleukin 6, interleukin 12, and ferritin were differentially expressed in women with and without endometriosis.

Evaluation of endometrial biomarkers for semi-invasive diagnosis of endometriosis.

OBJECTIVE: To test the hypothesis that specific proteins and peptides are expressed differentially in eutopic endometrium of women with and without endometriosis and at specific stages of the disease (minimal, mild, moderate, or severe) during the secretory phase. DESIGN: Patients with endometriosis were compared with controls. SETTING: University hospital. PATIENT(S): A total of 29 patients during the secretory phase were selected for this study on the basis of cycle phase and presence or absence of endometriosis. INTERVENTION(S): Endometriosis was confirmed laparoscopically and histologically in 19 patients with endometriosis of revised American Society for Reproductive Medicine stages (9 minimal-mild and 10 moderate-severe), and the presence of a normal pelvis was documented by laparoscopy in 10 controls. MAIN OUTCOME MEASURE(S): Protein expression of endometrium was evaluated with use of surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. The differential expression of protein mass peaks was analyzed with use of support vector machine algorithms and logistic regression models. RESULT(S): Data preprocessing resulted in differential expression of 73, 30, and 131 mass peaks between controls and patients with endometriosis (all stages), with minimal-mild endometriosis, and with moderate-severe endometriosis, respectively. Endometriosis was diagnosed with high sensitivity (89.5%) and specificity (90%) with use of five down-regulated mass peaks (1.949 kDa, 5.183 kDa, 8.650 kDa, 8.659 kDa, and 13.910 kDa) obtained after support vector machine ranking and logistic regression classification. With use of a similar analysis, minimal-mild endometriosis was diagnosed with four mass peaks (two up-regulated: 35.956 kDa and 90.675 kDa and two down-regulated: 1.924 kDa and 2.504 kDa) with maximal sensitivity (100%) and specificity (100%). The 90.675-kDa and 35.956-kDa mass peaks were identified as T-plastin and annexin V, respectively. CONCLUSION(S): Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis of secretory phase endometrium combined with bioinformatics puts forward a prospective panel of potential biomarkers with sensitivity of 100% and specificity of 100% for the diagnosis of minimal to mild endometriosis.

TRIzol treatment of secretory phase endometrium allows combined proteomic and mRNA microarray analysis of the same sample in women with and without endometriosis.

BACKGROUND: According to mRNA microarray, proteomics and other studies, biological abnormalities of eutopic endometrium (EM) are involved in the pathogenesis of endometriosis, but the relationship between mRNA and protein expression in EM is not clear. We tested for the first time the hypothesis that EM TRIzol extraction allows proteomic Surface Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry (SELDI-TOF MS) analysis and that these proteomic data can be related to mRNA (microarray) data obtained from the same EM sample from women with and without endometriosis. METHODS: Proteomic analysis was performed using SELDI-TOF-MS of TRIzol-extracted EM obtained during secretory phase from patients without endometriosis (n = 6), patients with minimal-mild (n = 5) and with moderate-severe endometriosis (n = 5), classified according to the system of the American Society of Reproductive Medicine. Proteomic data were compared to mRNA microarray data obtained from the same EM samples. RESULTS: In our SELDI-TOF MS study 32 peaks were differentially expressed in endometrium of all women with endometriosis (stages I-IV) compared with all controls during the secretory phase. Comparison of proteomic results with those from microarray revealed no corresponding genes/proteins. CONCLUSION: TRIzol treatment of secretory phase EM allows combined proteomic and mRNA microarray analysis of the same sample, but comparison between proteomic and microarray data was not evident, probably due to post-translational modifications.

Increased exposure to dioxin-like compounds is associated with endometriosis in a case-control study in women.

Although endometriosis is thought to be an environmental disorder initiated by dioxin exposure, this association is controversial. This study was performed to test the hypothesis that endometriosis occurs more often in women exposed to higher concentrations of dioxin-like compounds (DLC) than in those women exposed to lower concentrations. Plasma samples collected prior to laparoscopic surgery from 96 women with endometriosis and 106 control patients with a normal pelvis were measured for DLC concentrations using the dioxin-responsive chemical-activated luciferase expression bioassay. The results showed that concentration (mean+/-SD) of DLC was marginally higher in patients with endometriosis (22.3+/-9.3pg CALUX-TEQ/g lipid) than in controls (20.5+/-10.8pg). After categorization of patients in a group with 'low' plasma concentrations (<25th centile) and a group with 'high' plasma concentrations (>75th centile) of DLC, the age-adjusted odds ratio to have endometriosis was 2.44 (95% CI 1.04-5.70; P=0.04) for women with high concentrations of DLC and it increased to 3.01 (95% CI 1.06-9.04; P=0.03) when only women with moderate severe endometriosis were considered. In conclusion, women exposed to higher plasma concentrations of DLC were at higher risk of having endometriosis than women exposed to lower concentrations of DLC within normal environmental concentrations.

Reassessing the evidence for the link between dioxin and endometriosis: from molecular biology to clinical epidemiology.

A 1993 study reporting the link between exposure to dioxin and the risk of developing endometriosis in rhesus monkeys prompted many investigators to look suspiciously at dioxin. Since 1993, many in vitro, animal and epidemiological studies have been published, but the link between dioxin exposure and endometriosis is still unclear. The aim of our review is to present a summary of the biological effects of dioxin and its aryl hydrocarbon receptor, and to reassess the evidence presented in published, in vitro, preclinical and epidemiological studies regarding the association between dioxins and endometriosis. Although in vitro and animal studies provide results in support for a role of dioxins in the pathogenesis of endometriosis, caution should be exercised since these findings are mostly context dependent and since negative findings from these studies are rarely published. On the basis of our review of original epidemiological studies, no significant evidence can be found to support a link between dioxins and endometriosis in women. This observation can be explained by positive publication bias and by significant methodological problems associated with these studies, or by the absence of such a link. In conclusion, it seems that there is insufficient evidence at this moment in support of the hypothesis that dioxin exposure may lead to increased risk of developing endometriosis in women.

Role of cytokines in the endometrial-peritoneal cross-talk and development of endometriosis.

A clear picture of the dynamic relationship between the endometrium and peritoneum is emerging as both tissues may participate in the spontaneous development of endometriosis. Various adhesion molecules, pro-inflammatory cytokines and chemoattractants cytokines have emerged as central coordinators of endometrial-peritoneal interactions. The peritoneal microenvironment which consists of the peritoneal fluid, normal peritoneum and peritoneal endometriotic lesions may play an active role in the pathogenesis of endometriosis, by harbouring most inflammatory responses that are triggered by the presence of endometrial cells, leading to recruitment of activated macrophages and leukocytes locally. Menstrual endometrium has the ability to bond and invade the peritoneal tissue. In baboons intrapelvic injection of menstrual endometrium permits the study of early endometrial-peritoneal interaction in an in vivo culture microenvironment and can lead to important insight in the early development of endometriotic lesions. In this review, we discuss the roles of the endometrial-peritoneal interactions, not only in disease development but also in the broader process of aetiopathogenesis.

Endometrial and peritoneal expression of aromatase, cytokines, and adhesion factors in women with endometriosis.

OBJECTIVE: To examine messenger (m) RNA expression of aromatase, cytokines, and adhesion factors in women with and without endometriosis. DESIGN: Patients with endometriosis were compared with control patients. SETTING: University Hospital Gasthuisberg, Leuven, Belgium. PATIENT(S): A total of 35 patients who had laparoscopic surgery during the luteal phase (n = 20) or the menstrual phase (n = 15) were selected for this study based on cycle phase and presence/absence of endometriosis. INTERVENTION(S): Tissues of endometrium and macroscopically normal peritoneum were collected during hysteroscopy and laparoscopic surgery, respectively, from 24 women with revised American Society for Reproductive Medicine stage (rASRM) stages I-II (n = 12) and III-IV (n = 12) endometriosis and 11 control patients with normal pelvic. Tissue samples were selected from a tissue bank, based on the phase of the cycle (menstrual or luteal) and the presence/absence of endometriosis. MAIN OUTCOME MEASURE(S): The mRNA levels of aromatase, vimentin, vascular cell adhesion molecule 1 (VCAM-1), alpha(V) and beta(3) integrins, interleukin (IL)-1 beta, regulated on activation normal T-cell expressed and secreted (RANTES), and monocyte chemotactic protein 1 (MCP-1) were evaluated using real-time reverse transcriptase polymerase chain reaction. RESULT(S): During menstrual phase, increased endometrial mRNA levels of alpha(V) integrin, combined alpha(V)beta(3) integrins, and increased peritoneal IL-1 beta mRNA levels--but decreased peritoneal MCP-1 mRNA levels--were observed in women with endometriosis compared with control subjects. During luteal phase, endometrial mRNA levels of IL-1 beta and RANTES were increased in women with endometriosis compared with control subjects. Endometrial aromatase mRNA expression was higher in women with endometriosis than in control subjects in combined phases. Women with endometriosis had increased peritoneal mRNA expression of RANTES and VCAM-1 during menstrual compared with luteal phase. CONCLUSION(S): Aberrant mRNA expression of aromatase, cytokines, and adhesion factors in endometrium and peritoneum suggests that both tissues are involved in the pathogenesis of endometriosis.

Effect of recombinant human TNF-binding protein-1 and GnRH antagonist on mRNA expression of inflammatory cytokines and adhesion and growth factors in endometrium and endometriosis tissues in baboons.

OBJECTIVE: To evaluate the mechanism of action of recombinant human tumor necrosis factor (TNF)-binding protein-1 by assessing differential expression of messenger RNA (mRNA) for cytokines, matrix metalloproteinases, and growth and adhesion factors in baboons. DESIGN: Analysis of gene expression in a prospective randomized study. SETTING: University Fertility Center. ANIMAL(S): In the in vivo study, 14 baboons were randomly and subcutaneously (SC) treated with either phosphate-buffered saline (PBS), GnRH antagonist, or recombinant human TNF-binding protein-1 at the time of induction. In the ex vivo study, 4 baboons were treated by menstrual endometrium that had been incubated randomly with either PBS or recombinant human TNF-binding protein-1 before intrapelvic injection. INTERVENTION(S): In the in vivo study, analysis of 11 endometrial and 10 endometriosis biopsies included either PBS (n = 5), GnRH antagonist (n = 8), or recombinant human TNF-binding protein-1 (n = 8). In the ex vivo study, 2 endometrial and 4 endometriosis biopsies were analyzed from 4 baboons. MAIN OUTCOME MEASURE(S): The mRNA expression of TNF-alpha, IL-8, IL-6, transforming growth factor-beta (TGF-beta), vascular endothelial growth factor, intercellular adhesion molecule-1, matrix metalloproteinase-1, and regulated on activation, normal T-cell expressed and secreted were investigated using real-time reverse transcriptase-polymer chain reaction (PCR). RESULT(S): TGF-beta mRNA expression was decreased in endometriotic lesions from baboons treated with recombinant human TNF-binding protein-1 when compared with the placebo group. CONCLUSION(S): Except TGF-beta, mRNA expression of inflammatory cytokines and adhesion/growth factors is not affected in endometrial and endometriosis biopsies from baboons after induction of endometriosis combined with either systemic injection of recombinant human TNF-binding or GnRH antagonist or ex vivo treatment with recombinant human TNF-binding protein-1. Further studies are needed to elucidate the mode of action on how inhibition of TNF-alpha activity prevents the development of endometriosis.

Selective estrogen-receptor modulators and aromatase inhibitors: promising new medical therapies for endometriosis?

Endometriosis is an estrogen-dependent disease and estrogen-related pathways are imbalanced in women with endometriosis. One of the key enzymes in estrogen synthesis is aromatase. Inhibiting this pathway at several points is a promising idea for the treatment of endometriosis. The third generation of aromatase inhibitors is becoming more potent in efficacy, with fewer side effects than previous generations, but cotreatment with other hormones is needed to inhibit ovarian stimulation. Other components that promote estrogen synthesis such as COX-2 can also be potentially targeted. Selective estrogen-receptor modulators could also be interesting in view of their tissue-specific effect. However, all these new drugs are still in an early phase of development. At present, it is too early to conclude that aromatase inhibitors, COX-2 inhibitors or selective estrogen-receptor modulators really present any added value compared with the existing drugs that can be used to achieve hormonal suppression in the medical treatment of endometriosis.

Baboon model for the study of endometriosis.

Endometriosis is a benign, estrogen-dependent disease and is now recognized as an enigmatic disease owing to its various clinical manifestations and locations. The lack of a reliable and specific method for the early detection of endometriosis often results in delayed diagnosis. So far, research has born inadequate findings regarding understanding the basic etiology or pathophysiology of endometriosis. Animal models that accurately represent the cellular and molecular changes associated with the initiation and progression of human endometriosis have significant potential to facilitate the development of better methods for the early detection and treatment of endometriosis. A number of animal model systems have been developed for the study of this disease. These models replicate many of the known salient features of human endometriosis. This review provides an insight into the use of the baboon model for studies focused on understanding human endometriosis.

Endometriosis in African women.

Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue outside the uterine cavity. Although the prevalence of endometriosis is well documented in women living in developed countries, studies on the prevalence of this disease among African women are still wanting. The current view is that endometriosis rarely affects women of African descent. However, in African-American women in the USA, endometriosis is one of the common indications for major gynecological surgery and hysterectomy and is associated with a long hospitalization and high hospital charges. Endometriosis may be more commonly found in infertile Caucasian or African-American women than in African-Indigenous women, but it is likely that the true prevalence of endometriosis in African-Indigenous women is under reported owing to inadequate facilities and demands of specialized skills for adequate assessment of the pelvis and recognition of the various types and appearances of the disease. Understanding the prevalence of endometriosis among African women will be instrumental in proper management of this disease in the African continent.

Future of endometriosis research.

In women of reproductive age, health economic costs are estimated to be considerably higher for endometriosis than for conditions such as Crohn's disease, migraine and hypertension, and similar to the cost of diabetes. However, more awareness of endometriosis among patients and politicians is needed to create a better climate for research funding in the area of endometriosis in particular, and women's health in general. Recent collaboration between patients, physicians and politicians in the EU has shown that such efforts can be successful. Many arguments exist to organize the clinical care for women with advanced endometriosis in centers of excellence, but continuing education of primary-care physicians also remains a priority. New molecular techniques are resulting in new hormonal and nonhormonal targets for the noninvasive diagnosis and treatment of endometriosis. A future diagnostic serum assay might contain various elements from inflammatory serum markers to genetic/microarray/proteomics markers, owing to the multifactorial features of endometriosis.

Increased peritoneal and endometrial gene expression of biologically relevant cytokines and growth factors during the menstrual phase in women with endometriosis.

OBJECTIVE: To examine differential messenger RNA (mRNA) expression of relevant cytokines, metalloproteases, growth and adhesion factors in endometrium and peritoneum from women with endometriosis when compared with women without the disease during menstrual and luteal phases of the cycle. DESIGN: Patients with endometriosis were compared with control patients. SETTING: University hospital. PATIENT(S): A total of 35 patients (20 patients during the luteal phase and 15 patients during the menstrual phase) were selected for this study on the basis of cycle phase and presence or absence of endometriosis. INTERVENTION(S): In this study, endometriosis was laparoscopically and histologically confirmed in 24 women with endometriosis of revised American Society for Reproductive Medicine (ASRM) stage I-II (n = 12) and revised ASRM stage III-IV (n = 12), and the presence of a normal pelvis was documented by laparoscopy in 11 control patients. The macroscopically normal peritoneum tissues were collected from lateral wall left or right, near the colon ascendens or descendens. MAIN OUTCOME MEASURE(S): The expression levels were determined as ratios between the target molecules and beta-actin as housekeeping gene. RESULT(S): In women with endometriosis, peritoneal mRNA levels of matrix metalloproteinase (MMP)-3, transforming growth factor-beta, interleukin (IL)-6, and intercellular adhesion molecule-1 and endometrial mRNA levels of MMP-3, tumor necrosis factor (TNF)-alpha, and IL-8 were significantly higher during the menstrual phase when compared with luteal phase. During the menstrual phase of the cycle, both endometrial expression of TNF-alpha, IL-8, and MMP-3 mRNA levels and peritoneal expression of transforming growth factor-beta, IL-6, and intercellular adhesion molecule-1 mRNA levels were significantly higher in women with endometriosis when compared with controls. Immunohistochemical staining confirmed the presence of TNF-alpha in peritoneum and endometrium in both women with endometriosis and controls. CONCLUSION(S): Increased endometrial and peritoneal cytokine mRNA expression during menstruation may contribute to a pelvic inflammatory microenvironment favoring the development of endometriosis.

ProteinChip technology is a useful method in the pathogenesis and diagnosis of endometriosis: a preliminary study.

OBJECTIVE: To test the feasibility of ProteinChip (Ciphergen Biosystems, Inc., Fremont, CA) technology as a proteomic tool in discovering and identifying proteins that are differentially expressed in endometrium, endometriotic tissue, and normal peritoneum from women with and without endometriosis. DESIGN: Differential analysis of protein expression in women with and without endometriosis. SETTING: University hospital. PATIENT(S): A total of nine patients during their secretory phase (days 20-22) were selected for this study on the basis of cycle phase and presence/or absence of endometriosis. INTERVENTION(S): Twelve tissues used in the study included six endometrial biopsies from women with mild endometriosis (n = 3) and a normal pelvis (n = 3) as well as paired samples of peritoneal endometriotic lesions (n = 3) and macroscopically normal peritoneum biopsies (n = 3) from three women with endometriosis. MAIN OUTCOME MEASURE(S): Numerous expression differences were observed in the above comparisons, representing both up-regulation and down-regulation in protein and peptide expression levels. RESULT(S): Endometrial expression for a number of proteins and peptides in the range of 2.8-12.3 kDa was 3-24 times lower in women with endometriosis than in those without endometriosis. When compared with normal peritoneum, endometriotic lesions showed an increased expression for a set of proteins and peptides in the range of 3-96 kDa, and especially an up-regulated cluster of proteins between 22 and 23 kDa, identified to be transgelin, a smooth muscle actin-binding protein. CONCLUSION(S): This preliminary study demonstrated that differential protein profiling by using ProteinChip array technology is feasible, reproducible, and may be developed into a powerful tool for endometriosis research.

Recombinant human TNFRSF1A (r-hTBP1) inhibits the development of endometriosis in baboons: a prospective, randomized, placebo- and drug-controlled study.

Endometriosis is associated with chronic inflammation, including an increased macrophage activity with increased secretion of cytokines, such as tumor necrosis factor (TNF) or TNF superfamily member 2, previously known as TNFalpha. In the present study, we tested the hypothesis that recombinant human TNFRSF1A (r-hTBP1) can inhibit the development of endometriotic lesions in the baboon, an established model for the study of endometriosis. Endometriosis was induced using intrapelvic injection of menstrual endometrium in 20 baboons with a normal pelvis. In the first part of the study, 14 baboons were randomly assigned to subcutaneous treatment with r-hTBP1, placebo, or GnRH antagonist (positive control). In the second part of the study, menstrual endometrium from 6 baboons was randomly incubated with either PBS or r-hTBP1 before intrapelvic seeding. Video laparoscopy was performed 25 days later to document the number, surface area, and estimated volume of endometriotic lesions and adhesions; to calculate the revised American Fertility Society (rAFS) score and stage; and to confirm the histological presence of endometriosis. In the first part, baboons treated with r-hTBP1 or with Antide (Bachem) had a lower endometriosis rAFS score, a lower surface area and estimated volume of peritoneal endometriotic lesions, and a lower histological confirmation rate compared with controls. Because of less adnexal and cul-de-sac adhesions, the number of baboons with endometriosis of stage II, III, or IV was lower among baboons treated with r-hTBP1 or Antide than among controls. In the second part, the surface area of endometriotic lesions was lower, and less severe endometriosis was observed in r-hTBP1-treated baboons. No hypoestrogenic effects were observed in baboons treated with r-hTBP1. In conclusion, r-hTBP1 can effectively inhibit the development of endometriosis without hypoestrogenic effects in baboons.

Khat (Catha edulis) up-regulates testosterone and decreases prolactin and cortisol levels in the baboon.

The potential effect of Khat (Catha edulis, Celastraceae) on fertility in humans has not been elucidated. In this study, we used the olive baboon (Papio anubis, Cercopithecidae) to determine the effects of oral administration of khat on circulating hormones. In order to establish baseline hormonal levels, five male baboons were bled once a week for 1 month. The same baboons were then fed with crude khat juice extract once a week over a period of 2 months, and the effects on serum levels of cortisol, testosterone and prolactin determined using enzyme immunoassay (EIA) and radioimmunoassay (RIA). Subsequently, sampling was repeated for a further 1 month to determine the residual effect of khat. The results showed that khat administration causes a significant increase in the mean levels of testosterone while prolactin and cortisol levels were reduced. These effects were also evident 1 month post treatment and indicate khat may exert a transient effect on male fertility by interfering with the hormonal profiles.