Amenorrhea Research Articles

Identification of novel variants and candidate genes in women with 46,XX complete gonadal dysgenesis.

46,XX complete gonadal dysgenesis (46,XX-CGD) is a rare disorder of sexual development (DSD) characterized by primary amenorrhea and a lack of spontaneous pubertal development in individuals with a 46,XX karyotype despite the presence of female internal and external genitalia due to failure of bilateral ovarian development. The condition is genetically heterogeneous, and in most cases, its etiology is unknown. Determining the genetic cause would provide insights into potential targets for genetic diagnosis and counseling. To clarify the molecular mechanisms of 46,XX complete gonadal dysgenesis in the population of China, whole-exome sequencing (WES) was performed on DNA samples from patients with 46,XX-CGD. In silico analysis was conducted to predict the pathogenicity of the variants. We recruited 20 patients with 46,XX-CGD and identified 8 variants in 6 genes, including three homozygous variants in MCM9, POF1B, and PSMC3IP; compound heterozygous variants in TWNK; and three heterozygous variants in TP63 and INSRR, from 7 patients. These variants included 3 recurrent variants and 5 novel variants. This study identified several novel variants, broadening the variant spectrum of 46,XX-CGD. 46,XX-CGD is a genetically heterogeneous condition, and WES is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggest that WES is valuable for detecting 46,XX-CGD, which may lead to early interventions for patients.

17α-hydroxylase/17,20-lyase deficiency (17-OHD): A Meta-analysis of Reported Cases.

Homozygous pathogenic variants in the CYP17A1 gene result in defective activity of the steroidogenic enzymes 17α-hydroxylase/17,20-lyase resulting in the clinical syndrome 17-OHD characterised by hypertension, hypokalaemia, and disorders of sexual development. Pathogenic variants of CYP17A1 lead to complete or partial loss of enzymatic activity and clinical presentations of varying severity. This study aimed to examine relationships between CYP17A1 genotype and clinical presentation in a global cohort. We searched PubMed and Scopus for case reports and cohort studies reporting clinical data on patients with 17-OHD published between 1988 and 2022. Of 451 studies, 178 met inclusion criteria comprising a total of 465 patients. We pooled patient data and examined associations between causative variants and their clinical presentations. There were 465 unique patients with a mean age of 18·9 (9·0) years, 52·5% (n=244) were XY and 6·4% (n=29) were phenotypically male. Homozygous variants were seen in 48·0% (n=223) of patients. Common clinical presentations were hypertension (57·0%, n=256), hypokalaemia (45·4% n=211), primary amenorrhoea (38·3%, n=178), cryptorchidism (15·3%, n=71), and atypical genitalia (14·2%, n=66). Frequently occurring variants included p.Y329Kfs (n=86), p.D487_F489del (n=44) and p.W406R (n=39). More severe variants, such as p.Y329Kfs, were associated with hypocortisolism (p<0·05), combined hypokalaemia and hypertension (p<0·01), and DSD (p<0·01). 17-OHD is a rare, frequently misdiagnosed disease. Male patients are typically diagnosed earlier due to genital dysplasia associated with less severe variants, while female patients are typically diagnosed later due to primary amenorrhoea and hypertension. Patients presenting with DSD and hypertension should be investigated for 17-OHD.

Identification and Characterization of Novel FSHR Copy Number Variations Causing Premature Ovarian Insufficiency.

Follicle stimulating hormone (FSH) is a key pituitary gonadotropic hormone implicated in human fertility and is crucial for folliculogenesis and recruitment of new antral follicles. Variations in its receptor, FSHR, can lead to diverse reproductive phenotypes including ovarian hyperstimulation syndrome (OHSS) and premature ovarian insufficiency (POI). This study reports a novel case of FSHR-related ovarian insufficiency in a patient with primary amenorrhea, subnormal AMH levels, and delayed puberty. Genetic exploration revealed two compound heterozygous intragenic deletions of FSHR. Specifically, the patient inherited a maternally derived deletion spanning exons 5-10 and a paternally derived deletion involving exons 3-6. Through chromosomal microarray analysis (CMA), exome sequencing, long-range PCR, and Sanger sequencing, we characterized the breakpoints and confirmed the compound heterozygous deletions. The findings reveal a complete loss of function of both FSHR alleles, contributing to the patient's POI phenotype. This case emphasizes the complexity of genotype-phenotype correlations in FSHR-related disorders and the role of CNVs in POI phenotypes. Although these events are rare, our results advocate for the inclusion of CNV detection in the diagnostic workup of POI to ensure accurate diagnosis and better patient management.

CASE REPORT: AUTOIMMUNE HEPATITIS IN A 29-YEAR-OLD FEMALE WITH RECURRENT PREGNANCY LOSS

Autoimmune hepatitis (AIH) is a rare chronic liver disease characterized by a wide spectrum of symptoms ranging from asymptomatic to jaundice, which can be confusing in diagnosis because of their non-specificity and the presence of laboratory changes. This case report presents a 29-year-old woman with AIH and past history of repetitive pregnancy losses. She has been diagnosed with various problems such as two rounds of failed in vitro fertilization, five miscarriages and secondary amenorrhea. A liver biopsy proved AIH, and appropriate prednisolone and azathioprine therapy resulted in a positive change in her liver status. Early diagnosis and right management of AIHresulted in significant clinicalimprovement and normalization of liver function tests.

Imperforate Hymen: Rare Types

When the hymen, a thin membrane of stratified squamous epithelium circumscribing the vaginal introitus, does not spontaneously rupture during neonatal development, it is referred to as an imperforate hymen. An imperforate hymen is a rare cause of primary amenorrhea and can present with obstructive symptoms of the female genital and urinary tracts during the perinatal, pediatric, or adolescent years. Timely diagnosis and prompt treatment are critical. Specific pediatric and gynecologic knowledge and skills are necessary to provide comprehensive, patient-centered care. In addition to the anatomical and physiological aspects of imperforate hymen, its clinical presentation, and potential complications, the psychological impact on affected individuals must be understood. Best practices will ultimately improve patients’ quality of life and reproductive health outcomes. This activity reviews the evaluation and treatment of imperforate hymen and highlights the role of the interprofessional team in improving care for patients with this condition.

Risk factors for a decrease in bone mineral density in patients with Hodgkin's lymphoma.

BACKGROUND: Osteoporosis is characterized by a discharge of bone mass, which contributes to the development of pathological fractures. Hodgkin's lymphoma can cause a violation of bone microarchitectonics. The development of Hodgkin's lymphoma is characteristic of young people, on average from 16 to 35 years old. Early diagnosis of osteoporosis in young patients with Hodgkin's lymphoma is an urgent issue due to a prolonged asymptomatic decrease in bone mineral density, with the development of pathological fractures. AIMS: to study the risk factors for a decrease in bone mineral density in patients with Hodgkin's lymphoma who received pathogenetic therapy. MATERIALS AND METHODS: the study included 63 patients with Hodgkin's lymphoma and 30 volunteers from the control group. All patients answered the questionnaire questions in order to identify risk factors for osteoporosis. Common risk factors included: gender, age, body mass index; fractures in the history of the patient and his immediate family; taking hormone replacement therapy, proton pump inhibitors, glucocorticosteroids; the presence of concomitant diseases; the presence of amenorrhea in women; physical activity level and calcium intake. Specific factors include the use of chemotherapy drugs for the treatment of Hodgkin's lymphoma. The data obtained were subjected to statistical analysis in order to identify the most significant risk factors. RESULTS: osteopenia and osteoporosis are a serious complication of antitumor therapy of Hodgkin's lymphoma in young people. Unfortunately, today a small number of researchers are engaged in the problem of identifying predictors of osteoporosis in young patients with Hodgkin's lymphoma. Because of this study, the most significant risk factors for the development of osteoporosis were identified, namely low physical activity, taking proton pump inhibitors and glucocorticosteroids, as well as the development of secondary postcytostatic amenorrhea in women. CONCLUSIONS: timely diagnosis and prevention of osteoporosis in young patients will prevent a decrease in bone mineral density and reduce the risks of early disability in this category of patients.

Functional hypothalamic amenorrhoea and polycystic ovarian morphology: a narrative review about an intriguing association.

Functional hypothalamic amenorrhoea (FHA) is responsible for 20-35% of all cases of secondary amenorrhoea and, thus, is the second most common cause of secondary amenorrhoea after polycystic ovary syndrome (PCOS). A high number of patients with FHA reveal polycystic ovarian morphology (PCOM) on ultrasound. The combination of amenorrhoea and PCOM can lead to confusion. First, amenorrhoeic women with PCOM fulfil the revised Rotterdam criteria and, thus, can easily be misdiagnosed with PCOS. Moreover, it has been claimed that some women with FHA and concomitant PCOM differ from those without PCOM in terms of endocrine regulation and metabolic traits. The main focus of this article was on studies about FHA, which differentiated between patients with or without PCOM. The aim was to estimate the prevalence of PCOM and to look if it has an impact on pathophysiologic, diagnostic and therapeutic issues as well as on long-term consequences. Peer review original and review articles were selected from PubMed searches for this review. Searches were performed using the search terms 'polycystic AND functional hypothalamic amenorrhoea'. The reference lists of publications found were searched for relevant additional studies. The inclusion criteria for publications were: English language, patients' age ≥ 18 years, year of publication >1980, original studies, validated diagnosis of FHA, and validated diagnosis of PCOM using transvaginal ultrasound. The prevalence of PCOM in women with FHA varied from 41.9% to 46.7%, which is higher than in healthy non-PCOS controls. Hypothetically, the high prevalence might be due to a mixture of silent PCOM, as in the general population, and pre-existing PCOS. Several differences in metabolic and hormonal parameters were found between FHA-PCOM and FHA-non-PCOM patients. While oestrogen deficiency is common to both groups of patients, FHA-PCOM patients have a higher BMI, higher levels of anti-Müllerian hormone (AMH) and testosterone, a higher increase in LH in the course of a GnRH test, and lower sex hormone binding globulin (SHBG) levels than FHA-non-PCOM patients. The differential diagnosis between FHA-PCOM and PCOS, especially PCOS phenotype D (PCOM and oligo-/anovulation without hyperandrogenism), can be challenging. Several parameters have been suggested, which are helpful though not absolutely reliable. They include the typical causes for FHA (excessive exercise, energy deficit, and/or psychological stress), the serum levels of LH, testosterone, and SHBG, as well as the progestin challenge test. Whether FHA-PCOM has a different risk profile for long-term consequences concerning patients' metabolic and cardiovascular situation as well as their bone mass, is unclear. Concerning therapeutic aspects, there are only few data about FHA-PCOM compared to FHA-non-PCOM. To treat anovulation, the use of pulsatile GnRH treatment seems to be equally effective in both groups. Similar to FHA-non-PCOM patients, pulsatile GnRH therapy would be more efficient than exogenous gonadotropins in FHA-PCOM patients. Women with FHA-PCOM present a special sub-population of FHA patients. The diagnostic pitfall of FHA-PCOM should be emphasized in clinical guidelines about FHA and PCOS. The fact that almost half of the women with FHA have an ovarian follicle excess (i.e. PCOM) in face of low gonadotropin serum levels suggests that the intra-ovarian regulation of folliculogenesis is subject to individual variations, for unknown reasons, either genetic or epigenetic. Further studies are needed to investigate this hypothesis. Not applicable.

7407 Normosmic Idiopathic Hypogonadotropic Hypogonadism in Women: A Case Report and Comprehensive Review

Abstract Disclosure: E.G. Bustamante: None. M. Sulehri: None. I. Patoli: None. A. Karunakaran: None. Normosmic Idiopathic Hypogonadotropic Hypogonadism (nIHH) in Women: A Case Report and Literature ReviewIntroduction: IHH is a rare genetic disorder affecting gonadotropic-releasing hormone (GnRH) production and/or action, resulting in diminished sex steroid levels. Characterized by the absence of spontaneous pubertal development. In women, it manifests with normal adrenarche but absent thelarche and menarche. Our case highlight a late diagnosis of IHH in a 34-year-old woman with primary amenorrhea. Case report: A 34 year old lady with a history of primary amenorrhea sought evaluation. At age 16, she underwent assessment for short stature and primary amenorrhea, denying anosmia, headache, visual disturbances. Evaluation revealed bone age concordant with chronological age and normal MRI Brain. Pelvic ultrasound (US) showed small premenarchal uterus and ovaries. She initiated oral contraceptive pills (OCP) and experienced regular menses. Seeking fertility assistance at age 24, a normal Hysterosalpingogram was followed by successful delivery of twins after ovarian stimulation. Post-delivery menses did not resume and OCP was not restarted. Family history revealed a sister with irregular periods requiring OCP.Subsequently workup at age 30 showed Estradiol 22 pg/ml, FSH/LH 4.1/2.3 mUI/mL; normal PRL, TFT, DHEAS, 17OHP. Repeat Pelvic US showed normal uterus, endometrial stripe normal at 0.24 cm and non-visualized ovaries. PCOS testing negative for hyperandrogenism. Progesterone challenge resulted in no withdrawal bleeding. Brain MRI demonstrated a 2.2 x 1.3 mm hypoenhancing ovoid mass in the pars Intermedia of the pituitary gland suggestive of pituitary microadenoma. Pituitary axis hormonal testing was normal. Karyotype revealed 46 XX (normal female). Genetic evaluation identified a pathogenic variant (p.R35C) in GNRH1 gene. Her final diagnosis: nIHH. Discussion HH is diagnosed in 5% of all women with primary amenorrhea and is divided into 2 major categories: Kallmann syndrome and nIHH. The majority of known causes of HH can be attributed to mutations in KAL1, FGFR1, or GNRHR. The p.R35C variant has been associated with autosomal dominant nIHH. Diagnosis involves clinical suspicious, low LH/FSH and sex steroid levels, normal hypothalamic–pituitary imaging, and exclusion of differentials.Treatment goal for female focus on regular breast and uterine development, as well as the capability to conceive. Use of hormonal replacement therapy and/or gonadotropins or pulsatile GnRH for ovarian stimulation are essential. ConclusionWhile IHH predominantly affects men, limited literature explores its manifestation in women and its impact on fertility. The identification of a GNRH1-related nIHH variant highlights the role of genetic testing in specific HH diagnoses. Failure to diagnose in adolescence may compromise women overall well-being Presentation: 6/1/2024

8764 A Unique Case of Infertility in a Patient with NCCAH

Abstract Disclosure: M. Paravastu: None. R. Patel: None. Background: Non-Classic Congenital Adrenal Hyperplasia (NCCAH) in women often presents with hirsutism, acne, menstrual dysfunction, or infertility. Subfertility in patients with NCCAH can be attributed to menstrual disorders including oligomenorrhea or secondary amenorrhea. We report a unique case in which a patient with NCCAH with consistently normal menstrual cycles is experiencing infertility. Case Description: A 31 y/o female with no PMH was referred to our Endocrinology Clinic for evaluation of Infertility and elevated 17-Hydroxyprogesterone levels (17OHP). Patient has been having trouble conceiving for the past 2 years, no prior successful pregnancies. She started menstrual cycles at age 17, she reports having regular menstrual cycles. Prior to our evaluation, she was seen in Reproductive Endocrinology who completed hormonal and imaging evaluation. Elevated 17OHP: 286ng/dL. Rest of hormonal workup within normal range. Normal Pelvic Ultrasound. Hormonal workup was repeated in our clinic. 17OHP is elevated at 617.01ng/dL. Rest of lab work returned normal with DHEAS:218.9mcg/dL, TSH: 2.826mcUnits/mL, Free Testosterone: 5.4pg/mL, Prolactin:11.7ng/mL, Beta HCG: negative, LH: 13.5mUnits/mL, FSH: 5.3mUnits/mL, Estradiol 79pg/mL. Cosyntropin stimulation test was completed. Baseline AM 17OHP:469.78ng/dL, Baseline Cortisol: 17.9mcg/dL. 17OHP 30 minutes-post:1216.4ng/dL, Cortisol 30 minutes-post: 18.5mcg/dL. 17OHP 60 min-post: 1051ng/dL, Cortisol 60 minutes post:16.4 mcg/dL. Given Inconclusive Cosyntropin stimulation test results, Genetic Testing was recommended. Genetic testing returned positive for NCCAH, patient’s husband is not a carrier of this gene. She was started on Hydrocortisone therapy for treatment of infertility. Shortly after she started on hydrocortisone therapy, patient did successfully conceive, however the pregnancy later resulted in a miscarriage. Conclusion: Subfertility in patients in NCCAH is thought to be due to menstrual irregularities including oligomenorrhea or secondary amenorrhea. We report the first case of a woman with diagnosis of NCCAH who is experiencing infertility despite having normal menstrual cycles. Presentation: 6/1/2024

7521 Unmasking of PCOS after Microprolactinoma Treatment

Abstract Disclosure: F. Erenler: None. B. Aydogan Mathyk: None. Background: PCOS and prolactinomas are two of the leading causes of secondary amenorrhea. Hirsutism is a common finding for both diagnosis and can be the presenting symptom. We are presenting a case of secondary amenorrhea, initially diagnosed with microprolactinoma without signs of hyperandrogenism, which progressed to overt PCOS after prolactinoma treatment. Case: A 22-year-old female with history of Hashimoto’s hypothyroidism presented with secondary amenorrhea. Patient was on combined oral contraception pills (COC) for menstrual regulation and discontinued them with a desire of natural cycles. After the discontinuation of COC, her menstrual cycles did not return for four months and patient was subsequently found to have a microprolactinoma with prolactin (PRL) level 70.6 ng/mL - high (nl: 2.8-29.2 ng/mL), LH 6.1 mIU/mL (follicular phase: 1.9-12.5 mIU/mL), FSH 2.4 mIU/mL - low (follicular phase: 2.5-10.2 mIU/mL), androstenedione 132 ng/mL (follicular phase: 51-213 ng/mL), testosterone 36 ng/mL (nl: 2-45 ng/mL), AMH 33 ng/mL - high (nl: 1.02-14.63 ng/mL), DHEA-S 241 mcg/dL (nl: 44-286 mcg/dL), HCG neg. MR Sella showed a 0.5 cm hypoenchancing pituitary lesion, confirming the diagnosis of prolactinoma. Patient was started treatment with cabergoline 0.25 mg twice a week and PRL level trended down to 3.9 ng/mL. With normalization of PRL, patient started complaining of new onset hirsutism without return of her menses. Ferriman Gallway score was 8. Further workup showed elevated androgen markers: LH 25.7 mIU/mL - high (follicular phase: 1.9-12.5 mIU/mL), FSH 5.0 mIU/mL (follicular phase: 2.5-10.2 mIU/mL), PRL 4.7 ng/mL -low (nl: 4.8-23.2 ng/mL), androstenedione 341 ng/mL -high (41-262 ng/mL), E2 63.4 pg/mL (nl: 12.5-160 pg/mL), AMH 22.3 ng/mL – high (nl: 1.23-11.61 ng/mL), testosterone 94.7 ng/mL - high (nl: 10-55 ng/mL), DHEA-S 261 mcg/dL (nl:110-431.7 mcg/dL). ACTH stimulation test pursued to rule out NCAH and17-OH progesterone levels were within normal range after stimulation. Pelvis US obtained due to high suspicion for PCOS and was consistent with polycystic ovaries. The diagnosis of PCOS confirmed by Rotterdam criteria. Patient has phenotype A PCOS by the definition of NIH 2012 consensus. Conclusion: Hyperprolactinemia and pituitary adenomas can cause secondary amenorrhea. In our case, the treatment of hyperprolactinemia with cabergoline unmasked the underlying PCOS. The clinical and biochemical manifestation of PCOS became apparent following the removal of prolactin’s suppressive effect on GnRH. Presentation: 6/2/2024

12413 Reversal Of Congenital Hypogonadotropic Hypogonadism (CHH) In A Woman With A Heterozygous Inactivating Variant In GnRHR Gene

Abstract Disclosure: S.W. Nyunt: None. M. Phylactou: None. K. Koysombat: None. J. Tsoutsouki: None. A.C. Yeung: None. M. Young: None. A. Newman: None. A.N. Comninos: None. Y. Mamoojee: None. N. Pitteloud: None. R. Quinton: None. W.S. Dhillo: None. A. Abbara: None. Introduction: Congenital Hypogonadotropic Hypogonadism (CHH) is a rare genetic condition with central hypogonadism and pubertal failure affecting both sexes. Reversal of CHH is far less commonly reported in women in the literature. We presented a case of reversal of CHH in a woman with heterozygous GnRHR mutation and the use of kisspeptin in interrogating hypothalamic function. Case history: Our patient presented with primary amenorrhea and incomplete puberty aged 15 yrs. Based on high BMI from early adolescence, clinical hyperandrogenism, family history of polycystic ovary syndrome (PCOS) and insulin resistance, she was diagnosed with PCOS and commenced on a combined oral contraceptive (COC), achieving breast development.Aged 21yrs, she was reassessed for amenorrhea off COC. Biochemical assessment revealed hypogonadotropic hypogonadism (HH): LH 0.2 IU/L, FSH 0.3 IU/L, estradiol &amp;lt;92 pmol/L. She had a normal sense of smell and Tanner 4 breasts; MRI demonstrated normal olfactory bulbs and pituitary. The diagnosis was therefore revised to CHH and COC was restarted, later changed to HRT due to hypertension. A 22-gene CHH panel (R148) identified a heterozygous pathogenic variant c.3171&amp;gt;Gp in GNRHR.At reassessment off HRT aged 32yrs, she remained amenorrheic. Ultrasound showed normal ovarian morphology, antral follicle counts 17 and endometrial thickness 5.8mm; hormonal assays: LH 5.0 IU/L, FSH 8.3 U/L, estradiol 162 pmol/L, AMH 12.2 pmol/L, testosterone 1.6 nmol/L (RR &amp;lt;2.0), SHBG 35 nmol/L (RR 30-100 nmol/L).She then achieved 20kg weight loss (BMI 41.8 to 35.2 kg/m2) on GLP-1 agonist. GnRH test (Gonadorelin 100mcg) incremented LH from 5.16 to 44.46 IU/L and FSH from 6.47 to 15.27 IU/L at 60 mins. After an intravenous kisspeptin (9.6nmol/kg) bolus, LH rose from 5.05 to 29.99 IU/L, FSH from 6.68 to 13.91 IU/L. Off HRT, she began having regular cycles (estradiol 800 pmol/L). Discussion: CHH was diagnosed based on primary amenorrhea, HH and pathogenic GnRHR variant that would not, however, be expected to result in a productive phenotype in the absence of a second deleterious allele (oligogenicity occurs in 20% of CHH), so whole exome sequencing is awaited. Kisspeptin is a potent stimulator of hypothalamic GnRH neurons and can be used to interrogate hypothalamic function. Typically, gonadotrophin responses to kisspeptin are minimal in CHH. Thus, her kisspeptin response was not consistent with CHH at time of assessment, indicating reversal of CHH (seen in 20% of CHH, particularly with GnRHR variants). Notably, her kisspeptin response was higher than in healthy women, consistent with decreased hypothalamic function and potentially a ‘Female Obesity-Related Hypogonadism’. Our case highlights the value of interrogating hypothalamic function using kisspeptin, both for the diagnosis of CHH, and to identify alternate pathology, as well as to identify recovery of reproductive function in CHH reversal. Presentation: 6/1/2024

12413 Reversal Of Congenital Hypogonadotropic Hypogonadism (CHH) In A Woman With A Heterozygous Inactivating Variant In GnRHR Gene

Abstract Disclosure: S.W. Nyunt: None. M. Phylactou: None. K. Koysombat: None. J. Tsoutsouki: None. A.C. Yeung: None. M. Young: None. A. Newman: None. A.N. Comninos: None. Y. Mamoojee: None. N. Pitteloud: None. R. Quinton: None. W.S. Dhillo: None. A. Abbara: None. Introduction: Congenital Hypogonadotropic Hypogonadism (CHH) is a rare genetic condition with central hypogonadism and pubertal failure affecting both sexes. Reversal of CHH is far less commonly reported in women in the literature. We presented a case of reversal of CHH in a woman with heterozygous GnRHR mutation and the use of kisspeptin in interrogating hypothalamic function. Case history: Our patient presented with primary amenorrhea and incomplete puberty aged 15 yrs. Based on high BMI from early adolescence, clinical hyperandrogenism, family history of polycystic ovary syndrome (PCOS) and insulin resistance, she was diagnosed with PCOS and commenced on a combined oral contraceptive (COC), achieving breast development.Aged 21yrs, she was reassessed for amenorrhea off COC. Biochemical assessment revealed hypogonadotropic hypogonadism (HH): LH 0.2 IU/L, FSH 0.3 IU/L, estradiol &amp;lt;92 pmol/L. She had a normal sense of smell and Tanner 4 breasts; MRI demonstrated normal olfactory bulbs and pituitary. The diagnosis was therefore revised to CHH and COC was restarted, later changed to HRT due to hypertension. A 22-gene CHH panel (R148) identified a heterozygous pathogenic variant c.3171&amp;gt;Gp in GNRHR.At reassessment off HRT aged 32yrs, she remained amenorrheic. Ultrasound showed normal ovarian morphology, antral follicle counts 17 and endometrial thickness 5.8mm; hormonal assays: LH 5.0 IU/L, FSH 8.3 U/L, estradiol 162 pmol/L, AMH 12.2 pmol/L, testosterone 1.6 nmol/L (RR &amp;lt;2.0), SHBG 35 nmol/L (RR 30-100 nmol/L).She then achieved 20kg weight loss (BMI 41.8 to 35.2 kg/m2) on GLP-1 agonist. GnRH test (Gonadorelin 100mcg) incremented LH from 5.16 to 44.46 IU/L and FSH from 6.47 to 15.27 IU/L at 60 mins. After an intravenous kisspeptin (9.6nmol/kg) bolus, LH rose from 5.05 to 29.99 IU/L, FSH from 6.68 to 13.91 IU/L. Off HRT, she began having regular cycles (estradiol 800 pmol/L). Discussion: CHH was diagnosed based on primary amenorrhea, HH and pathogenic GnRHR variant that would not, however, be expected to result in a productive phenotype in the absence of a second deleterious allele (oligogenicity occurs in 20% of CHH), so whole exome sequencing is awaited. Kisspeptin is a potent stimulator of hypothalamic GnRH neurons and can be used to interrogate hypothalamic function. Typically, gonadotrophin responses to kisspeptin are minimal in CHH. Thus, her kisspeptin response was not consistent with CHH at time of assessment, indicating reversal of CHH (seen in 20% of CHH, particularly with GnRHR variants). Notably, her kisspeptin response was higher than in healthy women, consistent with decreased hypothalamic function and potentially a ‘Female Obesity-Related Hypogonadism’. Our case highlights the value of interrogating hypothalamic function using kisspeptin, both for the diagnosis of CHH, and to identify alternate pathology, as well as to identify recovery of reproductive function in CHH reversal. Presentation: 6/1/2024

7696 Ovarian Steroid Cell Tumor Presenting as Non-classical Adrenal Hyperplasia

Abstract Disclosure: V. Reddy: None. A. Gowda: None. V. Vattipally: None. D. Kunduru: None. IntroductionSteroid cell tumors(SCT) of the ovary make up less than 0.1% of all ovarian tumors. The three subtypes are stromal luteoma, Leydig cell tumor, and steroid cell tumor-not otherwise specified (NOS) which is the commonest subtype. Androgen excess is seen in 75% tumors and presents with virilization. Tumors are usually benign but maybe malignant in 25-43% cases. Factors predicting malignancy include size &amp;gt;7 cm, mitotic activity, necrosis, hemorrhage, and nuclear atypia. Case ReportA 29 y/o Caucasian female presented with secondary amenorrhea and hirsutism. History includes DM2,hypothyroidism,depression and morbid obesity. She reported early pubarche by age 8,menarche at age 13 and developed hirsutism and irregular menstrual cycles from age 15. No workup due to poor follow up until she saw PCP at age 21.She was diagnosed with PCOS and started on Metformin. Eventually referred to endocrinology at age 27, since amenorrhea and hirsutism persisted. On exam she had significant male pattern hair loss and hirsutism over face and body.She reported three first trimester miscarriages.Labs showed testosterone 370 ng/dl, 17 OHP 808 ng/dl, DHEAS 47 ng/dl, Estradiol 117 pg/ml, FSH 2.2 mIU/ml, LH 2.5 mIU/ml, androstenedione 319 ng/dl.Transvaginal US was unremarkable. She was diagnosed with non classical adrenal hyperplasia (NCAH) and started on treatment with prednisone 5 mg daily, drospirenone and spironolactone 100 mg daily.3 months later, labs showed 50% lowering of testosterone to 199 ng/dl and 17 OHP to 407 ng/dl.There was continued biochemical and clinical improvement at the next visit with 17 OHP 73 ng/dl and testosterone 55 ng/dl. Labs done 21 months after initial presentation, showed sudden dramatic rise in 17 OHP to 1148 ng/dl and testosterone to 639 ng/dl. Normal AFP, HCG, CEA, CA125, CA19-9, Inhibin A. CT showed 10.4 cm solid right ovarian mass and underwent right salpingo-oophorectomy. Pathology showed steroid cell tumor, NOS. Labs 1 month postoperatively showed complete normalization of testosterone to &amp;lt;3 ng/dl, 17 OHP to 11 ng/dl and DHEAS 0.66 ng/dl. Steroid therapy was tapered and discontinued. DiscussionWe present the case of a patient with ovarian SCT presenting as NCAH.SCTs are very rare accounting for only 0.1% of all ovarian tumors. Since they commonly secrete androgens, they present similarly to CAH or PCOS and may rarely even co-exist with CAH. Differentiating between NCAH and SCT is difficult especially when there is initial response to steroid therapy and imaging is unremarkable as with our patient. It is important to consider SCT in patients with hyperandrogenism even in the setting of elevated 17 OHP levels. Care should be taken to follow up both clinical and metabolic metrics closely and investigate if any change is noticed. Early diagnosis can prevent irreversible symptoms of hyperandrogenism. Presentation: 6/1/2024

6640 Utility of bilateral inferior petrosal sinus sampling for diagnosis and management of Cushing's disease in children ; a case report

Abstract Disclosure: V. leal: None. L. Socha: None. S.S. Awadalla: None. The causes of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) are Cushing's disease (CD) and ectopic ACTH syndrome (EAS). The differential diagnosis of CS and the localization of lesions in CD and EAS are often challenging. The utility of bilateral inferior petrosal sinus sampling (BIPSS), an important test in adults, is less defined in children.A 16-year-old girl was referred for evaluation and treatment of Cushing syndrome she experienced weight gain, secondary amenorrhea, and back pain. 24-hour urinary free cortisol and low-dose dexamethasone suppression tests suggested Cushing syndrome. Adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance reported a microadenoma. To rule ectopic ACTH syndrome, and localize the pituitary tumor, bilateral inferior petrosal sinus sampling (BIPSS) was performed with desmopressin to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to right ACTH-secreting pituitary microadenoma and underwent endoscopic endo-nasal transsphenoidal surgery.In conclusion , BIPSS can be a valuable tool not only for discriminating between pituitary origin and ectopic ACTH-secreting Cushing syndrome, but also for providing precise localization of pituitary adenomas, thereby facilitating appropriate treatment. Presentation: 6/1/2024

7696 Ovarian Steroid Cell Tumor Presenting As Non-classical Adrenal Hyperplasia

Abstract Disclosure: V. Reddy: None. A. Gowda: None. V. Vattipally: None. D. Kunduru: None. Ovarian Steroid Cell Tumor Presenting as Non-classical Adrenal Hyperplasia IntroductionSteroid cell tumors(SCT) of the ovary make up less than 0.1% of all ovarian tumors. The three subtypes are stromal luteoma, Leydig cell tumor, and steroid cell tumor-not otherwise specified (NOS) which is the commonest subtype. Androgen excess is seen in 75% tumors and presents with virilization. Tumors are usually benign but maybe malignant in 25-43% cases. Factors predicting malignancy include size &amp;gt;7 cm, mitotic activity, necrosis, hemorrhage, and nuclear atypia. Case ReportA 29 y/o Caucasian female presented with secondary amenorrhea and hirsutism. History includes DM2,hypothyroidism,depression and morbid obesity. She reported early pubarche by age 8,menarche at age 13 and developed hirsutism and irregular menstrual cycles from age 15. No workup due to poor follow up until she saw PCP at age 21.She was diagnosed with PCOS and started on Metformin. Eventually referred to endocrinology at age 27, since amenorrhea and hirsutism persisted. On exam she had significant male pattern hair loss and hirsutism over face and body.She reported three first trimester miscarriages.Labs showed testosterone 370 ng/dl, 17 OHP 808 ng/dl, DHEAS 47 ng/dl, Estradiol 117 pg/ml, FSH 2.2 mIU/ml, LH 2.5 mIU/ml, androstenedione 319 ng/dl.Transvaginal US was unremarkable. She was diagnosed with non classical adrenal hyperplasia (NCAH) and started on treatment with prednisone 5 mg daily, drospirenone and spironolactone 100 mg daily.3 months later, labs showed 50% lowering of testosterone to 199 ng/dl and 17 OHP to 407 ng/dl.There was continued biochemical and clinical improvement at the next visit with 17 OHP 73 ng/dl and testosterone 55 ng/dl. Labs done 21 months after initial presentation, showed sudden dramatic rise in 17 OHP to 1148 ng/dl and testosterone to 639 ng/dl. Normal AFP, HCG, CEA, CA125, CA19-9, Inhibin A. CT showed 10.4 cm solid right ovarian mass and underwent right salpingo-oophorectomy. Pathology showed steroid cell tumor, NOS. Labs 1 month postoperatively showed complete normalization of testosterone to &amp;lt;3 ng/dl, 17 OHP to 11 ng/dl and DHEAS 0.66 ng/dl. Steroid therapy was tapered and discontinued. DiscussionWe present the case of a patient with ovarian SCT presenting as NCAH.SCTs are very rare accounting for only 0.1% of all ovarian tumors. Since they commonly secrete androgens, they present similarly to CAH or PCOS and may rarely even co-exist with CAH. Differentiating between NCAH and SCT is difficult especially when there is initial response to steroid therapy and imaging is unremarkable as with our patient. It is important to consider SCT in patients with hyperandrogenism even in the setting of elevated 17 OHP levels. Care should be taken to follow up both clinical and metabolic metrics closely and investigate if any change is noticed. Early diagnosis can prevent irreversible symptoms of hyperandrogenism. Presentation: 6/1/2024

6942 Should there be a consensus statement about managing Inguinal Hernia In females? A Case of Delayed Diagnosis in Complete Androgen Insensitivity Syndrome (CAIS)

Abstract Disclosure: S. Echetebu: None. Introduction: Androgen Insensitivity Syndrome is usually due to a missense mutation that encodes part of the androgen receptor. More than 50% of females with CAIS present with inguinal hernias (4:1 female to male ratio). Previous CAIS studies have estimated the incidence of CAIS to be 0.8% to 2.4% in girls with inguinal hernias. 90% of the girls with CAIS will undergo inguinal hernia repair during childhood. The prevalence of germ cell tumors is estimated as 0.8% therefore, post-pubertal gonadectomy is now the recommended therapy for individuals with CAIS. Clinical Case: We present a case of a 15-year-old patient with primary amenorrhea who underwent bilateral inguinal hernia repair at the age of 5 weeks and was raised as a female. Initial ultrasound imaging at the age of 14 years revealed an absent uterus and complex hemorrhagic cysts of the ovaries. Further laboratory results revealed 46 XY chromosomal analysis, confirming her diagnosis of CAIS. Her laboratory values are: FSH 6.0 mIU/ml (1.0 to 18.6), Prolactin 15.6 ng/mL (&amp;lt;25), 17OHProgesterone 49 ng/dl (&amp;lt;265), Estradiol 30 pg/ml (&amp;lt;47), LH 17 mIU/ml (0.4 -11.7), Anti Mullerian Hormone 368 ng/ml (&amp;lt;13), Testosterone 629 ng/dl (&amp;lt;55 ). Upon our review of her past medical records from a different hospital, the operation note reports that her gonads resembled testes. Gonads were relocated in the abdomen without follow-up or consultation with an endocrinologist. Upon receiving her new diagnosis, the patient experienced significant emotional distress. As a result, both the patient and her family received psychological counseling and were referred to a genetic counselor to assess any potential risks for her younger sister. There is currently no consensus on the management of females with inguinal hernias in the available literature. It is widely accepted to perform gonadectomy. Currently, researchers at NIH are conducting an observational study on the benefits of additional delays in gonadectomy. Although most surgeons are familiar with this condition, it would be beneficial for families and patients to have an early diagnosis and provide appropriate education regarding future sexual encounters and fertility concerns. Conclusion: We propose to initiate a consensus statement for pediatricians, surgeons, and endocrinologists to perform systematic genetic testing in females with inguinal hernia. Such testing may include either a buccal mucosal smear, karyotype, or skin biopsy in all females with inguinal hernias. If the family chooses to delay orchiectomy, it is recommended that during hernioplasty, the testes should be repositioned in a location that allows for easy monitoring using annual imaging. By adopting this methodology, we can increase awareness about the effects of diagnosis and foster discussions among healthcare professionals regarding suitable management options. Presentation: 6/3/2024

6934 Nutritional Factors and Endothelial Dysfunction in Women with Functional Hypothalamic Amenorrhea

Abstract Disclosure: E.R. Uddenberg: None. N. Safwan: None. G. Cook-Wiens: None. O. Obrutu: None. M. Saadedine: None. M.D. Hurtado: None. S. Faubion: None. M.D. Pisarska: None. S.L. Berga: None. J.E. Manson: None. C.N. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) occurs in women of reproductive age and is a common form of secondary amenorrhea that results in hypoestrogenemia and hypercortisolemia. The underlying cause of FHA is due to a mismatch between energetic intake and expenditure that often manifests as disordered eating, excessive exercise, and psychosocial stress. Previous research identified that 1 in 3 women with FHA had endothelial dysfunction, a preclinical marker for cardiovascular disease. We sought to evaluate the nutrition content in young women with FHA compared to eumenorrheic controls and further assess the relationship to endothelial dysfunction. Methods: We enrolled 30 women with FHA and 29 eumenorrheic controls, not on hormones. FHA was defined as ≥3 consecutive months of amenorrhea, estradiol &amp;lt;50 pg/mL, FSH&amp;lt;10 mIU/L, and LH&amp;lt;10 mIU/L, and exclusion of polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction, and pregnancy. Eumenorrheic controls had monthly menses with ovulation (progesterone ≥4 ng/mL). Vascular function was measured using EndoPAT 2000 (Itamar® Medical Ltd) to calculate the reactive hyperemic index (RHI). An RHI ≤1.67 indicates endothelial dysfunction. Nutritional intake was collected using a 3-day food diary and analyzed using ESHA Research Food Processor® Nutrition Analysis. Percent (%) recommendation values for nutrition content comparison were calculated based on height, weight, and age. Statistical analysis included Analysis of Variance and Kruskal Wallis test with nonparametric variables reported as median [IQR]. Results: The mean age and BMI of FHA and controls were 26.4 ± 6.2 yrs and 30.3 ± 3.7 yrs (p=0.008), and 21.6 ± 6.2 and 21.8 ± 2.0 kg/m2 (p=0.16), respectively. The median months of FHA amenorrhea was 12 months [5.0, 34.0]. After adjusting for age, there was no difference in caloric intakes in women with FHA compared to controls (1783.9 [1465, 2011] kcal vs. 1731.9 [1578, 1982] kcal, p=0.73); however FHA has higher intake of grams of protein (84.2 [74, 112] g vs. 74 [59, 92] g, p=0.0036), and higher grams of dietary fiber (30.1 [22, 43] g vs. 17.3 [15, 23] g, p=0.0037), respectively. In women with FHA, endothelial dysfunction was associated with a higher % recommended calories (p=0.0098), calories from fat (p=0.02), grams of saturated fat (p=0.03), and grams of carbohydrates (p=0.049). Conclusions: Our results demonstrate that women with FHA consumed similar daily calories, although more grams of protein and dietary fiber than controls. In women with FHA, higher calories, calories from fat, grams of saturated fat and carbohydrates were associated with endothelial dysfunction. Future studies should aim to identify other factors related to endothelial dysfunction among women with FHA and whether some FHA phenotypes are associated with more endothelial dysfunction than others. Presentation: 6/1/2024

6934 Nutritional Factors and Endothelial Dysfunction in Women with Functional Hypothalamic Amenorrhea

Abstract Disclosure: E.R. Uddenberg: None. N. Safwan: None. G. Cook-Wiens: None. O. Obrutu: None. M. Saadedine: None. M.D. Hurtado: None. S. Faubion: None. M.D. Pisarska: None. S.L. Berga: None. J.E. Manson: None. C.N. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) occurs in women of reproductive age and is a common form of secondary amenorrhea that results in hypoestrogenemia and hypercortisolemia. The underlying cause of FHA is due to a mismatch between energetic intake and expenditure that often manifests as disordered eating, excessive exercise, and psychosocial stress. Previous research identified that 1 in 3 women with FHA had endothelial dysfunction, a preclinical marker for cardiovascular disease. We sought to evaluate the nutrition content in young women with FHA compared to eumenorrheic controls and further assess the relationship to endothelial dysfunction. Methods: We enrolled 30 women with FHA and 29 eumenorrheic controls, not on hormones. FHA was defined as ≥3 consecutive months of amenorrhea, estradiol &amp;lt;50 pg/mL, FSH&amp;lt;10 mIU/L, and LH&amp;lt;10 mIU/L, and exclusion of polycystic ovary syndrome, hyperprolactinemia, thyroid dysfunction, and pregnancy. Eumenorrheic controls had monthly menses with ovulation (progesterone ≥4 ng/mL). Vascular function was measured using EndoPAT 2000 (Itamar® Medical Ltd) to calculate the reactive hyperemic index (RHI). An RHI ≤1.67 indicates endothelial dysfunction. Nutritional intake was collected using a 3-day food diary and analyzed using ESHA Research Food Processor® Nutrition Analysis. Percent (%) recommendation values for nutrition content comparison were calculated based on height, weight, and age. Statistical analysis included Analysis of Variance and Kruskal Wallis test with nonparametric variables reported as median [IQR]. Results: The mean age and BMI of FHA and controls were 26.4 ± 6.2 yrs and 30.3 ± 3.7 yrs (p=0.008), and 21.6 ± 6.2 and 21.8 ± 2.0 kg/m2 (p=0.16), respectively. The median months of FHA amenorrhea was 12 months [5.0, 34.0]. After adjusting for age, there was no difference in caloric intakes in women with FHA compared to controls (1783.9 [1465, 2011] kcal vs. 1731.9 [1578, 1982] kcal, p=0.73); however FHA has higher intake of grams of protein (84.2 [74, 112] g vs. 74 [59, 92] g, p=0.0036), and higher grams of dietary fiber (30.1 [22, 43] g vs. 17.3 [15, 23] g, p=0.0037), respectively. In women with FHA, endothelial dysfunction was associated with a higher % recommended calories (p=0.0098), calories from fat (p=0.02), grams of saturated fat (p=0.03), and grams of carbohydrates (p=0.049). Conclusions: Our results demonstrate that women with FHA consumed similar daily calories, although more grams of protein and dietary fiber than controls. In women with FHA, higher calories, calories from fat, grams of saturated fat and carbohydrates were associated with endothelial dysfunction. Future studies should aim to identify other factors related to endothelial dysfunction among women with FHA and whether some FHA phenotypes are associated with more endothelial dysfunction than others. Presentation: 6/1/2024

7277 Diabetic Ketoacidosis As The First Manifestation Of Ectopic Cushing’s Syndrome

Abstract Disclosure: R.S. Medeiros: None. Introduction: Ectopic Cushing’s Syndrome (ECS) represents 10-20% of all ACTH-dependent CS, and the majority of cases arise from lung carcinoids. These indolent lesions usually evolve clinically over 6-24 months, whereas carcinomas are associated with faster onset of ECS. Diabetic Ketoacidosis (DKA) as a presenting manifestation of Cushing’s Syndrome (CS) is very rare, with the few cases published to date related to Cushing’s disease. Clinical Case: A 42-year-old woman was admitted in the emergency room with DKA and COVID-19. During stabilization, florid CS was clinically suspected. She reported a 6-month history of secondary amenorrhea, lack of concentration and memory, easy bruising, proximal myopathy with frequent falls evolving to daily life dependency from relatives. She also reported a 2-month diagnosis of dyslipidemia, Diabetes and hypertension, and a diagnosis of atypical pneumonia 6 months ago. Physical exam showed typical cushingoid appearance, especially for marked limb sarcopenia and proximal myopathy. An overnight dexamethasone suppression test (morning cortisol: 25.7 ug/dL), 24h urinary free cortisol (UFC; 1072.5 ug/dL; reference: &amp;lt;176) and serum cortisol at 23h00 (25.5 ug/dL) confirmed CS. ACTH-dependent CS was diagnosed. She had non-suppressible serum cortisol in high dose dexamethasone suppression test, and CRH stimulation test was suggestive of Cushing’s disease only by a 20% rise of cortisol at 30 minutes. Pituitary MRI was normal. Inferior Petrosal Sinus sampling was postponed for several months due to healthcare strikes. The patient started 750 mg of metyrapone in three divided doses but rapidly decreased the dose and stopped it due to clinical resolution of CS, a dramatic improvement of all glucocorticoid-related comorbidities leading to discontinuation of statin, insulin, main oral anti-hyperglycemic and antihypertensive medications, and normal midnight salivary cortisol and 24h UFC. She remained in this eucortisolemic state for 12 months. Thoracic CT scan revealed thymic hyperplasia and a 25x15 mm well-defined nodule in the lingula. A 68Ga-DOTANOC PET/CT showed a single uptake in the same lung region. The patient underwent lingulectomy plus excisional biopsy of interlobar lymph nodes, and pathology revealed a low-grade neuroendocrine tumor (Ki67&amp;lt;2%, &amp;lt;2 mitosis) without involved lymph nodes. The patient is weaning off from physiologic doses of hydrocortisone. Conclusion: DKA can rarely be the presenting manifestation of severe CS, including ECS. Clinicians should suspect on this etiology of DKA based on clinical signs and cumulative morbidity not typical of a young patient. This hint would lead to the expedite implementation of targeted therapies for initial stabilization of the CS patient, and the timely institution of a proper diagnostic approach and definitive treatment of this challenging patients. Presentation: 6/2/2024

7590 Bone Mineral Content In Women With Functional Hypothalamic Amenorrhea Compared To Eumenorrheic Controls And Recently Menopausal Women

Abstract Disclosure: N. Safwan: None. E.R. Uddenberg: None. M.D. Hurtado: None. M. Saadedine: None. S.S. Faubion: None. O. Obrutu: None. S.L. Berga: None. M.D. Pisarska: None. C. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) accounts for 30% of secondary amenorrhea due to suppression of GnRH associated hypercortisolemia resulting in chronic hypoestrogenemia. FHA occurs as a result of varying combinations of psychosocial stress, excessive exercise, and/or disordered eating. FHA is associated with decreased bone mineralization; however, it is unknown how bone health compares to older, menopausal women who also experience bone loss. We compared dual-energy x-ray absorptiometry (DXA) bone health parameters among women with FHA, eumenorrheic controls, and recently menopausal women and evaluated if previous oral contraceptive (OC) use among FHA women has an impact on bone mineral density (BMD). Methods: This cross-sectional study included 20 women with FHA, 9 eumenorrheic controls, and 12 recently menopausal women who underwent hip and spine DXA. All participants were not on hormone therapy. FHA was defined as amenorrhea &amp;gt;3 consecutive months, estradiol &amp;lt;50 pg/ml, FSH &amp;lt;10 mIU/L, and LH &amp;lt;10 mIU/L, excluding other etiologies including PCOS, prolactinoma, thyroid dysfunction, and pregnancy. Eumenorrheic controls had self-reported monthly menses confirmed with day 22-24 progesterone &amp;gt;3 ng/ml. Recently menopausal women had natural menopause &amp;lt;3 years of final menstrual period, and FSH &amp;gt;30 mIU/L. DXA bone health parameters were measured using Lunar iDXA (GE) including BMD from the lumbar spine (L1-L4) and hip. Statistical analysis included nonparametric testing with pairwise Wilcoxon rank sum and Kruskal Wallis, reported as median [interquartile ranges]. Results: By design, the mean age of FHA was 28 ± 6 yr, 29 ± 3 yr for controls, and 54 ± 2 yr for recently menopausal women (p&amp;lt;0.0001). There were no differences in weight or BMI among the groups (p=0.27, p=0.30, respectively). BMD L1-L4 differed among the three groups with 1.10 g/cm2 [1.00, 1.24] for FHA, 1.18 [1.15, 1.29] for eumenorrheic controls, and 1.02 [0.96, 1.08] for menopausal women (p=0.002). Pairwise analysis revealed a significant difference in BMD L1-L4 between FHA and controls (p=0.04) and menopausal women and controls (p=0.009, age-adjusted). However, there was no difference in BMD L1-L4 between FHA and menopausal women (p=0.08, age-adjusted). In FHA women with previous OC use, BMD L1-L4 was not different from eumenorrheic controls (p=0.20), while BMD L1-L4 differed from that of recently menopausal women (p=0.004). These differences were not observed at the hip. Conclusion: Compared to eumenorrheic controls, lumbar spine BMD in young women with FHA (mean age 28 yr) was similar to recently menopausal women (mean age 54 yr) emphasizing the profound bone impact of FHA. Previous OC use seems to mitigate FHA bone mineralization changes. Future studies should investigate if bone health differs among women with FHA based on underlying cause and if previous OC use plays a role in maintaining bone health. Presentation: 6/3/2024