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Results for “Fertility Pattern Method”

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PubMed1983

Large bowel cancer in women in relation to reproductive and hormonal factors: a case-control study.

A community-based case-control study of the effect of reproductive factors on risk of large bowel cancer in Australia is described. The study involved 155 cases (99 colon cancer, 56 rectal cancer) and 311 controls who were interviewed with regard to pregnancies and their outcomes, lactation, menstrual history, and oral contraceptive (OC) use. Increasing parity was associated with a decreasing risk of colon cancer; para 0, relative risk (RR)=1; para 1-2, RR=0.9, 95% confidence interval (CI)=0.4-1.8; para greater than or equal to 3, RR=0.4, 95% CI=0.2-0.8; later age at first live birth (AFLB) was associated with increasing risk (AFLB less than or equal to 21 yr, RR=1; 22-25 yr, RR=2.3, 95% CI=1.0-5.5; greater than or equal to 26 yr, RR=2.7, 95% CI=1.2-6.2). These effects were independent of each other. Parity appeared to exert its predominant effect on risk of cancer of the right colon. OC use was more common among controls than cases (RR=0.5; 95% CI=0.3-1.2 for ever vs. never users) and showed a dose-response effect in multiple logistic analysis. The pattern of point-estimate RR for rectal cancer was largely congruent with those for colon cancer but was not significantly different from 1.0.

Adult↗

PubMed1998

New once-a-month injectable contraceptives, with particular reference to Cyclofem/Cyclo-Provera.

Once-a-month injectable contraceptives containing a progestogen and an estrogen have been developed that disrupt vaginal bleeding patterns less than the widely used progestogen-only preparations. Pharmacokinetic studies were undertaken of dosages and ratios of the progestogens and the respective estrogens. In Phase III clinical trials, annual pregnancy rates were below 0.4% for Mesigyna (norethisterone enanthate/estradiol valerate, Schering AG, Berlin, Germany) and below 0.2% for Cyclofem (MPA/E2C) (medroxyprogesterone acetate/estradiol cypionate, Aplicaciones Farmaceuticas, SA, Mexico and PT Tunggal, Indonesia). More than two-thirds of women had predictable, regular cycles, and discontinuation due to bleeding-related problems occurred less than half as often as with progestogen-only injectables. With MPA/E2C, return to fertility is similar to that observed with other hormonal or intrauterine methods, and both products have little effect on lipids or hemostasis. Introductory trials of MPA/E2C in 12000 women with 100000 woman-months of experience confirmed the high efficacy of the product in routine use. The use of MPA/E2C in a non-reusable injection device, Uniject (Becton Dickinson, Franklin Lakes, NJ) is discussed. Once-a-month hormonal contraceptives have been shown to provide a safe contraceptive option for all women and an alternative for women who wish to use injectable formulations that cause less disruption in vaginal bleeding and minimal side effects.

Clinical Trials, Phase III as Topic↗

PubMedDate not supplied

Induction of maternal tolerance to fetal alloantigens by RANTES production.

PROBLEM: Previous studies have demonstrated a requirement for RANTES (regulated on activated normal T-cell expressed, and secreted) at immune privileged sites; we have investigated the role of RANTES in the induction of maternal-fetal tolerance. METHOD OF STUDY: Endometrial and peripheral T lymphocytes were obtained from women with recurrent pregnancy losses (RPLs) and fertile women. RANTES modulation by progesterone or paternal alloantigens was measured by enzyme-linked immunosorbent assay or flow cytometry analysis. RESULTS: Progesterone significantly increased intracellular RANTES expression in CD4+ and CD8+ endometrial T cells. Moreover, alloreactive lymphocytes from RPL patients produced lower RANTES levels when compared with those from fertile women. At the local level, treatment with recombinant RANTES induced a decrease in CCR5 and CXCR4 messenger RNA that correlated with an increase in T-bet expression. RPL patients and normally fertile women express RANTES similarly, but differ in their patterns of RANTES receptor expression. CONCLUSION: RANTES may be implicated in the local induction of a Th1-type response necessary for successful implantation. Altered response to RANTES stimulation among some RPL patients may be responsible for poor pregnancy outcomes.

Abortion, Habitual↗

PubMed2005

Non-homogeneous hyperechogenic echo pattern three days after frozen embryo transfer is associated with lower pregnancy rates.

OBJECTIVE: To evaluate the association of mid-luteal phase echo patterns and pregnancy rates (PRs) following frozen embryo transfer (ET). METHODS: Sonographic evaluation of endometrial echo patterns was performed three days after ET in the first frozen ET cycle of women < 40 years of age who used their own oocytes as well as all donor oocyte recipients. RESULTS: The distribution of echo patterns and clinical PRs were similar in women using their own eggs and women who used donor oocytes; therefore all data was combined. The clinical PR was 49.5% with a hyperechogenic echo pattern vs 38.8% with a non-hyperechogenic pattern, p = .007. CONCLUSION: A larger study of frozen ET and mid-luteal echo pattern now demonstrates conclusions similar to the data from fresh ET in hyperstimulated in vitro fertilization (IVF)-ET cycles in that failure to attain a hyperechogenic echo pattern three days after ET is associated with lower pregnancy rates.

Adult↗

PubMed1993

Photoperiod, temperature, and regional patterns of conceptions in the USA.

Twenty-two years of monthly values of birth data for the USA, 1967 through 1988, were analyzed by visual inspection. The data were transformed to remove the influence of length of month and of linear trend, and the values were lagged 9 months to approximate the time of conception. Then, 11-year monthly averages were obtained and plotted as standard scores. Thus two 11-year sets of data were independently analyzed, providing the opportunity of replication. Four distinct temporal patterns were found, differing in month of occurrence of the initial trough and peak and the relative sizes of the two troughs; these characteristics of the temporal pattern change systematically with latitude in the eastern and midwestern states. Data from two other continents, the United Kingdom and Australia, also were analyzed using the same method and found to exhibit a temporal pattern during the year similar to the northern states of the USA. Two biologically relevant variables, temperature and photoperiod, were considered as possible controllers and regulators of the annual rhythmicity. Comparisons of the trends in conceptions with these environmental variables, and inspections of the temperatures and photoperiods at which peaks and troughs in conceptions were found, indicated that these environmental variables could not account for the annual rhythmicity in conceptions.

Birth Rate↗

PubMed2026

Failures to maintain CpG-methylation of CoRSIVs in bovine sperm are associated with low sire conception.

In brief: Correlated regions of systemic interindividual epigenetic variation (CoRSIVs) are genomic regions with CpG-methylation patterns that differ between individuals, yet are consistent between tissues, within the same individual. Analyzing two groups of Holstein bull methylomes-nine with a high sire-conception rate (SCR) and nine with a low SCR-we found that a common type of CoRSIVs was significantly associated with reduced SCR and is thus suggested as a biomarker for SCR because it was highly methylated in sperm, but failed to retain hypermethylation in the gametes of males with low SCR. Abstract: Correlated regions of systemic interindividual epigenetic variation (CoRSIVs) are genomic regions with CpG-methylation patterns that differ between individuals, yet are consistent between tissues, within the same individual; therefore, their methylation can be profiled in bodily fluids that are easily obtained, such as blood and semen. Bearing in mind the simple epigenetic profiling of CoRSIVs, we tested whether this type of differentially methylated region (DMR) is associated with bovine fertility. Sequence Read Archive (SRA) meth BLAST was used to estimate CoRSIVs methylation status in 18 healthy, representative, and age-matched Holstein bulls, among which nine had high (H) sire-conception rate (SCR), and the other nine had low (L) SCR (group averages of SCR: 3.3 ± 0.6 and -3.8 ± 1.8, respectively). This method was also applied to morula and trophoblast SRA methylomes. Analysis with meth BLAST was effective for most (80%) CoRSIVs and showed that CoRSIVs are reprogrammed during blastocyst formation, although this method was incapable of specifically determining the methylation level in CoRSIVs with retrotransposons. In sperm, the effect of global methylation was evident in a common (25%) type of CoRSIVs that is highly (94.5% ± 4.3%) methylated in sperm. Specifically, a failure to retain hypermethylation in the sperm plus strand was significantly (p < 0.00025) indicative of low SCR. Comparing global DNA methylation using the latter type of CoRSIVs between sperm and blood can be used as a better biomarker for fertility than using other differentially methylated regions with more complex epigenetics.

Animals↗

PubMed1999

Fertility patterns after appendicectomy: historical cohort study.

OBJECTIVE: To examine fertility patterns in women who had their appendix removed in childhood. DESIGN: Historical cohort study with computerised data and fertility data for this cohort and for an age matched cohort of women from the Swedish general population. The cohorts were followed to 1994. SETTING: General population. PARTICIPANTS: 9840 women who were under 15 years when they underwent appendicectomy between 1964 and 1983; 47 590 control women. MAIN OUTCOME MEASURES: Diagnoses at discharge. Distributions of age at birth of first child among women with perforated and non-perforated appendix and women who underwent appendicectomy but were found to have a normal appendix compared with control women by using survival analysis methods. Parity distributions at the latest update of the registry were also examined. RESULTS: Women with a history of perforated appendix had a similar rate of first birth as the control women (adjusted hazard ratio 0.95; 95% confidence interval 0.88 to 1. 04) and had a similar distribution of parity at the end of follow up. Women who had had a normal appendix removed had an increased rate of first births (1.48; 1.42 to 1.54) and on average had their first child at an earlier age and reached a higher parity than control women. CONCLUSION: A history of perforated appendix in childhood does not seem to have long term negative consequences on female fertility. This may have important implications for the management of young women with suspected appendicitis as the liberal attitude to surgical explorations with a subsequently high rate of removal of a normal appendix is often justified by a perceived increased risk of infertility after perforation. Women whose appendix was found to be normal at appendicectomy in childhood seem to belong to a subgroup with a higher fertility than the general population.

Adolescent↗

PubMed1986

Some aspects of the development of the peripheral autonomic nervous system in the abdomen and the pelvis of the rat. Preliminary results.

The development of the relation of the left vagus nerve with the esophagus and the stomach and the relation of the pelvic plexus with the urinary bladder during the last week before birth has been studied by means of the AChE in toto method (Baljet and Drukker 1975, Bloot et al. 1984). It has been established that the gastric branches can be traced as far as the greater curvature until the 18th day. On the 18th day the stomach increases as much in size that on the 19th day these branches can not be traced so far any more. The growth pattern of the left vagus nerve, the stomach and the esophagus has been visualized graphically. In contrast to the previous observations on the stomach the urinary bladder increases gradually in size. However the nerve branches which run towards the bladder show a sudden increase in length on the 20th day after fertilization.

Abdomen↗

PubMedDate not supplied

The dynamics of contraceptive use in Peru.

In 1986, the Demographic and Health Surveys project administered the first six-year calendar history of events that included women's contraceptive use and their reasons for discontinuation in experimental surveys in Peru and the Dominican Republic. In this report the experimental survey from Peru is examined to demonstrate how the calendar data can be used to calculate multiple increment-decrement life table rates of contraceptive discontinuation--including contraceptive failure, method switching, and abandonment of use--and of resumption of method use following discontinuation. These analyses reveal that nearly half of all Peruvian women who begin to use a method will stop using it within one year; 29 percent of women discontinue method use for nonpregnancy-related reasons within one year of initiating use. Women who switch methods do so frequently, and many will return to a method used previously, or move on to a third method. Women who become pregnant after abandoning contraceptive use have similar contraceptive-use patterns to women who experience a contraceptive failure.

Adult↗

PubMed2006

New approaches for male fertility control: HE6 as an example of a putative target.

Reversible contraceptive methods for males are still not available. During the last few years several marketing studies have clearly shown that men and women would welcome a situation where men could assume responsibility for family planning. Schering AG and Organon are currently collaborating to develop a hormonal method for male fertility control based on the combination of etonogestrel as gestagenic component and testosterone undecanoate. To further optimize male contraceptives in terms of improved efficiency, rapid onset, reversibility, fewer side effects and a convenient method of application, a search for innovative non-hormonal approaches was started. During the last few years, numerous proteins were identified which play a specific role in male fertility. These proteins have first to fulfil a set of indication-specific criteria before a drug discovery process can be initiated. The most important criteria for a putative target protein are tissue-selective expression, crucial biological function in fertility, drugable properties and feasibility of assay development for high-throughput-screening and lead optimization. The G-protein-coupled receptor HE6 was selected as target and the above selection criteria were applied. HE6 displays a preferred epididymis-specific expression pattern and belongs to the superfamily of GPCRs, which are well known to be drugable with small molecules. A knockout mouse was generated which revealed an infertility phenotype with the onset occurring 6 weeks after initiation of spermatogenesis at the latest. Surprisingly, no epididymis-specific phenotype was observed. Instead, the reabsorption of testicular fluid along the efferent ducts was strongly affected. No further obvious side effects were observed in male or female mice. This study with HE6 exemplifies how targets for male contraception have to be validated before drug development can start.

Animals↗

PubMedDate not supplied

On the evolutionary coexistence of parasite strains.

Classical models of parasite competition show that coexistence is impossible if different strains give complete cross-immunity. However, parasite coexistence is possible if some of the model assumptions are changed. For instance, coexistence is impossible if density-dependence operates only in hosts' fertility, but surprisingly becomes possible if hosts' mortality is density-dependent. Parasite strains can also coexist if a host already infected with one strain may become infected by another strain (superinfection). I examine here if these reasons for coexistence carry over to evolutionary timescales: in other words, suppose that potentially a continuum of parasite strains may arise by mutations; will evolution arrive at a halt? in that case, will only one or several strains persist? The paradigm and methods of adaptive dynamics are used in this study. It is found, under reasonably general assumptions, that a unique evolutionarily stable state for virulence, alpha(*), exist for both models. However, the pattern of the invasibility plots depends on the shape of the trade-off (between virulence and transmissibility, or superinfection rates) functions, and on the host demography. In many cases, the state alpha(*) is evolutionarily stable only with respect to small mutations, not to larger ones; hence, evolutionary dynamics will bring virulence to alpha(*) only if mutations are sufficiently small; for larger mutations, evolutionary dynamics are more complex and still mainly unresolved.

Animals↗

PubMedDate not supplied

Role of growth hormone in ovarian physiology and onset of puberty.

OBJECTIVE: To review the role of growth hormone (GH) in the timing of puberty and to summarize the interactions between the somatotrophic and reproductive axes. The use of recombinant GH in patients with GH deficiency is outlined. METHODS: A MEDLINE search was performed of English language manuscripts dealing with the role or use of GH in puberty and reproduction. RESULTS: Growth hormone appears to augment the rate of sexual maturation once a pubertal pattern of gonadotropin secretion is established. Growth hormone may modulate gonadal steroid production by increasing hepatic insulin-like growth factor-I production or by acting directly on GH receptors, localized recently in the granulosa cells and corpus luteum in the human ovary. Patients with isolated GH deficiency exhibit short stature, truncal adiposity, and delayed puberty. However, patients with isolated GH deficiency ultimately undergo spontaneous puberty, and women with GH receptor defects are fertile, suggesting that GH most likely acts as a co-gonadotropin to augment the actions of FSH and LH on estradiol and progesterone production. CONCLUSIONS: Growth hormone appears to increase the rate of sexual maturation once a pubertal pattern of pituitary gonadotropin secretion is established. The ovary is a site of GH reception and action, where it can potentiate steroidogenesis and gametogenesis either directly or through endocrine actions. Continued basic and clinical research is needed to characterize further the role of GH in reproductive physiology.

Animals↗

PubMed1996

The role of the cytoskeleton in polarity and morphogenesis of algal cells.

Selected algal species continue to serve as model organisms for the study of cell growth and cellular morphogenesis. Recent improvements in immunohistochemical and microinjection methods have helped to consolidate our views of the role of the cytoskeleton as a generator of spatial patterns in the cytoplasm before cellular morphogenesis. Progress has also been made in the discovery and characterization of molecular components of both the cytoskeleton and the extracellular matrix (ECM). Studies on the oocytes of fucoid brown algae have demonstrated that the ECM serves an active role in controlling cell shape and in defining the developmental fate of a cell. Actin, transmembrane proteins of the beta-integrin type, and vitronectin-like proteins in the ECM have been discussed as important elements in polar axis formation in the early steps of post-fertilization development. The mechanism of cell expansion has been investigated in the large coenocytic cells of the siphonoclad green algae. It was shown that the alignment of cell wall microfibrils in these cells depends on the degree of order in the cortical microtubule system. However, in contrast to earlier hypotheses, microtubules do not appear to function as physical boundaries guiding the paths of cellulose synthesizing terminal complexes in the plane of the plasma membrane. Recent work on the giant unicellular green alga Acetabularia has revealed dynamic reorganizations of the actin cytoskeleton during the course of apical morphogenesis. Actin has also been suggested to play a role, in more subtle ways, in the establishment of membrane prepatterns during cellular morphogenesis of the desmid green alga Micrasterias, prepatterns that predict regions of future surface expansion.

Cell Polarity↗

PubMed2002

Efficient soybean transformation using hygromycin B selection in the cotyledonary-node method.

The efficiency of soybean [Glycine max (L.) Merrill] transformation was significantly increased from an average of 0.7% to 16.4% by combining strategies to enhance Agrobacterium tumefaciens-mediated T-DNA delivery into cotyledonary-node cells with the development of a rapid, efficient selection protocol based on hygromycin B. Wounded cotyledonary-node explants were inoculated with A. tumefaciens carrying either a standard-binary or super-binary plasmid and co-cultivated in the presence of mixtures of the thiol compounds, L-cysteine, dithiothreitol, and sodium thiosulfate. Transformed shoots began elongating only 8 weeks after co-cultivation. Southern analysis confirmed integration of the T-DNA into genomic DNA and revealed no correlation between the complexity of the integration pattern and thiol treatment applied at co-cultivation. All T(0) plants were fertile and the majority of the lines transmitted the beta-glucuronidase (GUS) phenotype in 3:1 or 15:1 ratios to their progenies.

Agrobacterium tumefaciens↗

PubMed2007

Ambient manganese exposure is negatively associated with human sperm motility and concentration.

BACKGROUND: Occupational and experimental animal studies indicate that exposure to high levels of manganese impairs male fertility, but the effects of ambient manganese in humans are not known. METHODS: We measured blood levels of manganese and selenium in 200 infertility clinic clients in a cross-sectional study. Correlations between metals and semen variables were determined, adjusting for other risk factors. Outcomes were low motility (<50% motile), low concentration (<20 million/mL), or low morphology (<4% normal). We also investigated dose-response relationships between quartiles of manganese exposure and sperm parameters. RESULTS: High manganese level was associated with increased risk of low sperm motility (odds ratio = 5.4; 95% confidence interval = 1.6-17.6) and low sperm concentration (2.4; 1.2-4.9). We saw a U-shaped dose-response pattern between quartiles of manganese exposure and all 3 sperm parameters. CONCLUSION: Ambient exposure to manganese levels is associated with a reduction in sperm motility and concentration. No adverse effects were seen for high selenium.

Adult↗

PubMed2026

Mapping ovarian cellular and molecular landscape across the lifespan of women: a scoping review.

BACKGROUND: With growing interest in ART, fertility preservation, and postmenopausal health of women, reproductive medicine is increasingly focused on characterizing oocytes and ovarian tissue composition, as well as understanding the molecular mechanisms that guide ovarian function throughout its lifecycle. High-throughput omics technologies have enabled the characterization of different molecular layers, leading to substantial advances in our understanding of their complex dynamics. However, not all molecular aspects are studied equally, and studies examining the same modalities often show inconsistencies, underscoring the need for data standardization and highlighting the potential for using transformative artificial intelligence and machine-learning (AI/ML) methods for ovary studies. OBJECTIVE AND RATIONALE: This study aims to evaluate how multi-omic studies have advanced our understanding of the ovarian lifecycle from fetal development to postmenopause. We systematically reviewed published studies that have investigated molecular/omic layers, including the genome, methylome, transcriptome, and proteome throughout ovarian development and aging. Our analysis identified key molecular and cellular patterns, highlighted inconsistencies across studies and addressed gaps in data analysis, interpretation, and reproducibility to guide future research. SEARCH METHODS: We conducted a systematic literature search of Medline (PubMed), Embase (Ovid), and Web of Science Core Collection (Clarivate) using a combination of controlled and free text terms for human ovary, oogenesis, folliculogenesis, ovary development and (epi)genome, transcriptome, proteome, and multi-omic mechanisms to find relevant articles published before August 2025. To focus the scope of the current review, studies of domesticated and farm animals, rodents and other model organisms, non-human primates, as well as those examining various human ovarian pathologies were excluded. OUTCOMES: The search identified 23 546 studies for screening, of which 637 full-text studies were assessed for eligibility. Subsequently, we extracted data from 121 studies. Most studies analyzed the transcriptome of oocytes, granulosa cells, and ovarian tissue from reproductive-age individuals (n = 91), with fewer studies examining samples from individuals of advanced reproductive age (n = 45) and fetal (n = 16) samples. Transcriptome analyses were most common (n = 103, 85%), followed by proteome (n = 19, 16%) and epigenome (n = 14, 12%) studies. We found substantial variation in how studies defined and reported participants' groups as well as in their sequencing technologies and data analysis methods, with a lack of standardized reporting of background clinical information, data analysis methods, and pipeline details. The key findings underscore the prevailing consensus on genes defining major ovarian cell types and their roles throughout the ovarian lifespan, from prenatal development to postmenopausal transformation. This review highlighted the underrepresentation of certain patient groups, particularly prepubertal and peri-/postmenopausal individuals, among researched populations, due to obvious clinical and ethical reasons. WIDER IMPLICATIONS: This scoping review offers a comprehensive overview and benchmark of the current state of high-throughput omics-based research on ovarian cellular composition and molecular dynamics. To address these shortcomings, we propose general recommendations for multi-omics ovary studies and emphasize the necessity for more thorough multi-omic data integration by effectively applying novel AI/ML approaches. They can potentially improve the quality of multi-omics analyses at both single-cell and tissue levels despite limited sample sizes and enable integration of molecular profiling data with clinical and radiology datasets, enabling a more comprehensive understanding of ovarian biology. Such advancements can enhance reproducibility of research findings and guide future research to deepen our understanding of ovarian biology and ultimately support the development of medical technologies for better preserving fertility and alleviating infertility. REGISTRATION NUMBER: A protocol was published a priori on the Open Science Framework (https://osf.io/z38gb/).

Female↗

PubMed2006

Live offspring produced by mouse oocytes derived from premeiotic fetal germ cells.

Mature mouse oocytes currently can be generated in vitro from the primary oocytes of primordial follicles but not from premeiotic fetal germ cells. In this study we established a simple, efficient method that can be used to obtain mature oocytes from the premeiotic germ cells of a fetal mouse 12.5 days postcoitum (dpc). Mouse 12.5-dpc fetal ovaries were transplanted under the kidney capsule of recipient mice to initiate oocyte growth from the premeiotic germ cell stage, and they were recovered after 14 days. Subsequently, the primary and early secondary follicles generated in the ovarian grafts were isolated and cultured for 16 days in vitro. The mature oocytes ovulated from these follicles were able to fertilize in vitro to produce live offspring. We further show that the in vitro fertilization offspring were normal and able to successfully mate with both females and males, and the patterns of the methylated sites of the in vitro mature oocytes were similar to those of normal mice. This is the first report describing premeiotic fetal germ cells able to enter a second meiosis and support embryonic development to term by a combination of in vivo transplantation and in vitro culture. In addition, we have shown that the whole process of oogenesis, from premeiotic germ cells to germinal vesicle (GV)-stage oocytes, can be carried out under the kidney capsule.

Animals↗

PubMed2002

Macroprolactinemia revisited: a study on 106 patients.

The predominance of high molecular weight PRL, or macroprolactinemia, has long been known in hyperprolactinemic patients with maintained fertility. Among 1,106 consecutive patients investigated for hyperprolactinemia in our center over a 10-yr period, serum PRL chromatography was performed in 368 cases because of discordant clinical, biological, or neuroradiological findings. We prospectively studied the 106 patients with macroprolactinemia (96 women, 6 men, 4 children) and compared them with the 262 hyperprolactinemic patients with a normal PRL elution pattern. We concluded the following: 1) the incidence of macroprolactinemia in our hyperprolactinemic population was at least 10%; 2) despite preserved fertility with uneventful pregnancies, some of the usual symptoms of hyperprolactinemia were present; 3) mean PRL values were 61 +/- 66 microg/liter (range, 20-663) and exceeded 100 microg/liter in 8.5% of patients; 4) PRL levels usually remained stable over time; 5) on dopaminergic therapy, PRL returned to normal in 21 of 45 treated patients; 6) during follow-up of 7 pregnancies, PRL increased to supraphysiological levels in 5; and 7) pituitary magnetic resonance imaging was normal in 78% of patients or revealed diverse pituitary lesions, including adenomas (n = 5). A diagnostic method for macroprolactinemia should be available to all centers to avoid unnecessary hormonal or radiological investigations and treatments.

Adenoma↗