Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.
Humans ; Azoospermia/therapy* ; Male ; Testosterone/therapeutic use* ; Anabolic Agents/adverse effects* ; Clomiphene/therapeutic use* ; Chorionic Gonadotropin/therapeutic use* ; Follicle Stimulating Hormone/therapeutic use* ; Spermatogenesis/drug effects* ; Androgens/adverse effects*

PURPOSE: To characterize the population of hypogonadal men who presented to a tertiary academic urology clinic and evaluate risk factors for primary vs. secondary hypogonadism. MATERIALS AND METHODS: We evaluated all men with International Classification of Diseases-9 diagnosis codes R68.82 and 799.81 for low libido, 257.2 for testicular hypofunction, and E29.1 for other testicular hypofunction at a tertiary academic medical center from 2013 to 2017. We included men who had testosterone (T) and luteinizing hormone (LH) drawn on the same day. We classified men based on T and LH levels into eugonadal, primary, secondary, and compensated hypogonadism. Risk factors including age, body mass index (BMI) over 30 kg/m2, current smoking status, alcohol use greater than 5 days per week, and Charlson comorbidity index greater than or equal to 1 were investigated and measured in each group using the eugonadal group for reference. RESULTS: Among the 231 men who had both T and LH levels, 7.4%, 42.4%, and 7.4% were classified as primary, secondary, and compensated hypogonadism, respectively. Only elevated BMI was associated with secondary hypogonadism compared to eugonadal men (median BMI, 30.93 kg/m2 vs. 27.69 kg/m2, p=0.003). BMI, age, comorbidities, smoking, or alcohol use did not appear to predict diagnosis of secondary hypogonadism. CONCLUSIONS: Secondary hypogonadism appears to be the most common cause of hypogonadism among men complaining of low T and decreased libido at a tertiary academic medical center. Secondary hypogonadism is associated with elevated BMI and therefore obesity should be used as a marker to evaluate men for both T and LH levels.
Academic Medical Centers* ; Body Mass Index* ; Classification ; Clomiphene ; Comorbidity ; Diagnosis ; Humans ; Hypogonadism* ; Libido ; Luteinizing Hormone ; Male ; Obesity ; Risk Factors ; Smoke ; Smoking ; Tertiary Care Centers ; Testosterone ; Urology

BACKGROUND: Clomiphene citrate is used as the first line drug for anovulatory infertility treatment. When a woman fails to ovulate using clomiphene at maximum dose, letrozole is used as a second line drug.

OBJECTIVE: To determine association between a patient's age and body mass index (BMI) and their response to clomiphene citrate or letrozole in the treatment of anovulation-related infertility.

MATERIALS AND METHODS: The authors reviewed 147 patient records from January 2011 to August 2016 and investigated the age, BMI and response of patients when given clomiphene or letrozole for ovulation induction.

RESULTS: Ninety-nine (99) patients received clomiphene citrate while the other 118 patients received letrozole. Those who responded positively to clomiphene were at least 35 years old (72.2%) or had above normal BMI (61.5%). Patients who responded positively to letrozole were at least 35 years old (95%) and were categorized with above normal BMI (82.9%). The authors found that patients who are older than 35 years of age are more likely to respond to letrozole compared to younger patients.

CONCLUSION: This study found no significant association between BMI and response to either Letrozole or Clomiphene. Patients who are more than 35 years old are more likely to respond to letrozole, compared to younger patients. 

Human ; Clomiphene ; Body Mass Index

OBJECTIVE: To observe the effects of abdominal acupuncture and the periodic therapy of Chinese herbal medicine on follicular development and endometrial receptivity in the patients with infertility induced by ovulation failure and differentiated as kidney deficiency in TCM. METHODS: A total of 84 patients with infertility induced by ovulation failure and differentiated as kidney deficiency were randomized into a combined therapy group (27 cases), an abdominal acupuncture group (27 cases) and a western medication group (30 cases). In the combined therapy group, abdominal acupuncture and the periodic treatment of Chinese herbal medicine was provided. In the abdominal acupuncture group, the simple abdominal acupuncture therapy was used. In the western medication group, clomiphene citrate (CC) and human chorionic gonadotrophin (HCG) prescribed. The treatment for one menstrual cycle was taken as one session and 3 sessions of treatment were required except the pregnancy. The folicle development, endometrial thickness and morphology, menstrual condition and TCM symptom score were observed before and after treatment in the three groups, and the clinical efficacy was evaluated. RESULTS: After treatment, the ovulation was recovered to different degrees in the three groups. The ovulation rate was 59.3% (16/27) in the combined therapy group, 55.6% (15/27) in the abdominal acupuncture group and 53.3% (16/30) in the western medication group. The difference was not significant in comparison among the three groups (>0.05). After treatment, the endometrial thickness in the periovulatory period was increased as compared with the thickness before treatment in the combined therapy group and the abdominal acupuncture group (both <0.05). After treatment, the endometrial thickness in the combined therapy group was higher than the western medication group (<0.05). In comparison before and after treatment, the difference in the endometrial morphology was significant in the combined therapy group and the abdominal acupuncture group (both <0.05). In comparison between the combined therapy group and the western medication group, the difference in the endometrial morphology was significant after treatment (<0.05). After treatment, the menstrual condition and TCM symptom score in the combined therapy group and the abdominal acupuncture group were all improved as compared with those before treatment (all <0.05). The score of menstrual condition in the combined therapy group was higher than the western medication group (<0.05) and TCM symptom score in the combined therapy group and abdominal acupuncture group was higher than the western medication group after treatment (all <0.05). The total effective rate was 88.9% (24/27) in the combined therapy group and was 92.6% (25/29) in the abdominal acupuncture group, which was higher than 56.7% (17/30) in the western medication group (<0.01). There was no adverse reaction in the combined therapy group and the abdominal acupuncture group. CONCLUSION Abdominal acupuncture combined with the periodic therapy of Chinese herbal medicine improve the menstrual condition and relieve the clinical symptoms of infertility induced by ovulation failure of kidney deficiency in the patients and the therapeutic effects are better than the medication with CC + HCG. This combined therapy improves the ovulation rate and the endometrial receptivity at periovulatory stage to increase the pregnancy rate. There is no adverse reaction discovered in clinical practice.
Acupuncture Therapy ; Clomiphene ; Drugs, Chinese Herbal ; Female ; Humans ; Infertility, Female ; Ovulation ; Pregnancy

OBJECTIVETo compare the difference in the therapeutic effects on ovulation disorder in polycystic ovary syndrome (PCOS) between the combined therapy of electroacupuncture and clomiphene and the single medication of clomiphene and to explore the effect mechanism.

METHODSA total of 80 patients of PCOS were randomized into an acupuncture plus medication group (40 cases) and a medication group (40 cases). In the medication group, since the 5th day of menstruation or medicine-withdrawal bleeding, clomiphene was prescribed for oral administration, continuously for 5 days. In the acupuncture plus medication group, the medication was the same as the medication group. Additionally, 30 min electroacupuncture (continuous wave, 2 Hz) was applied to Qihai (CV 6), Guanyuan (CV 4), Zigong (EX-CA 1), Dahe (KI 12), Sanyinjiao (SP 6), Zhongji (CV 3), Diji (SP 8), Shenshu (BL 23), Sanjiaoshu (BL 22) and Ciliao (BL 32), etc. The treatment started on the 5th day of menstruation or medicine-withdrawal bleeding, once every two days, 3 times a week. One cycle of menstruation or 1 month was taken as one course. The treatment cycles were 3 months in the two groups. The level of estradiol (E) and progesterone (P) in the serum, the endometrial thickness and morphology, ovulation rate and clinical pregnancy rate, as well as the clinical therapeutic effects were compared after treatment in the two groups.

RESULTSTwo cases were dropped out because the herbal medicine was taken simultaneously in the acupuncture plus medication group. In the medication group, the medication was discontinued in 3 cases due to gastrointestinal adverse reactions. The total effective rate was 86.8% (33/38) in the acupuncture plus medication group, better than 64.9% (24/37) in the medication group (<0.05). The ovulation rate in the acupuncture plus medication group was higher than that in the medication group [(86.8%, 33/38) vs (64.9% 24/37), <0.05]. The pregnancy rate in the acupuncture plus medication group was higher than the medication group in tendency, without significant difference [21.1% (8/38) vs 16.2% (6/37), >0.05]. After treatment, the results of endometrial thickness and morphology (A-type rate) in the acupuncture plus medication group were better than those in the medication group (<0.01, <0.05). After treatment, regarding the levels of E and P in the serum in the window period of implantation, the results in the acupuncture plus medication group were higher remarkably than those in the medication group (both <0.01).

CONCLUSIONThe combined intervention of electroacupuncture and clomiphene achieves the definite effects of ovulation and pregnancy promotion in PCOS. It remarkably increases the levels of E and P in the serum, the endometrial thickness and A-type rate. The therapeutic effects of the combined intervention are remarkably better than those of the simple application of clomiphene. This combined intervention is safe and tolerable for the adverse reactions. The effect mechanisms may be related to the improvements of estrogen, progestin and endometrial receptivity.

Acupuncture Therapy ; Clomiphene ; therapeutic use ; Combined Modality Therapy ; Electroacupuncture ; Female ; Humans ; Infertility, Female ; therapy ; Ovulation ; Ovulation Induction ; Polycystic Ovary Syndrome ; therapy ; Pregnancy ; Pregnancy Rate

Heterotopic pregnancy or the coexistence of an intrauterine and an extrauterine pregnancy occurs in about 1 out of 30,000 pregnancies. Between assisted reproductive techniques and ovulation induction, it is said to occur more commonly with the former. The patient presented in this case is a 29 year old primigravid who underwent ovulation induction with clomiphene citrate and was later on diagnosed to have both an intrauterine and a non-viable extrauterine pregnancy. The management for this kind of pregnancy can be medical, surgical or expectant. The patient in this case was managed expectantly. This case study presents a review of literature on heterotopic pregnancy, and describes how this rare type of pregnancy developed in this index patient, how it is diagnosed and managed, and to showcase how expectant management can be a safe option for cases of heterotopic pregnancy.
Pregnancy, Heterotopic ; Pregnancy, Ectopic ; Clomiphene

CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations.
Adult ; Chromatography, High Pressure Liquid ; Clomiphene/blood/metabolism/*therapeutic use ; Cytochrome P-450 CYP2D6/*genetics ; Estrogen Antagonists/analysis/metabolism/therapeutic use ; Female ; Genotype ; Humans ; Infertility/*drug therapy/genetics ; Ovulation Induction ; Phenotype ; *Polymorphism, Genetic ; Republic of Korea ; Tandem Mass Spectrometry

OBJECTIVE: This study aimed to determine the threshold of anti-Müllerian hormone (AMH) as predictor of follicular growth failure in polycystic ovary syndrome (PCOS) patients treated with clomiphene citrate (CC). METHODS: Fifty female subjects with PCOS were recruited and divided into two groups based on successful and unsuccessful follicular growth. Related variables such as age, infertility duration, cigarette smoking, use of Moslem hijab, sunlight exposure, fiber intake, body mass index, waist circumference, AMH level, 25-hydroxy vitamin D level, and growth of dominant follicles were obtained, assessed, and statistically analyzed. RESULTS: The AMH levels of patients with successful follicular growth were significantly lower (p=0.001) than those with unsuccessful follicular growth (6.10±3.52 vs. 10.43±4.78 ng/mL). A higher volume of fiber intake was also observed in the successful follicular growth group compared to unsuccessful follicular growth group (p=0.001). Our study found the probability of successful follicle growth was a function of AMH level and the amount of fiber intake, expressed as Y=–2.35+(–0.312×AMH level)+(0.464×fiber intake) (area under the curve, 0.88; 95% confidence interval, 0.79–0.98; p<0.001). CONCLUSION: The optimal threshold of AMH level in predicting the failure of follicle growth in patients with PCOS treated with CC was 8.58 ng/mL.
Body Mass Index ; Clomiphene* ; Female ; Humans ; Infertility ; Ovarian Follicle ; Polycystic Ovary Syndrome* ; Smoking ; Sunlight ; Vitamin D ; Waist Circumference

OBJECTIVETo explore the best therapy for infertility caused by polycystic ovary syndrome (PCOS).

METHODSOne hundred and twenty patients were randomized into three groups, a clomi-phene group (group A), an acupuncture-moxibustion + Chinese medicine group (group B) and a clomiphene + acupuncture-moxibustion+ Chinese medicine group (group C), 40 cases in each one. In the group A, since the 5th day of menstruation, clomiphene was prescribed for oral administration. In the group B, on the 5th day of menstruation, warm needling therapy was applied at Zhongji (CV 3), Guanyuan (CV 4), Guilai (ST 29), etc. Additionally, the Chinese herbal medication for tonifying the kidney and activating blood circulation was provided. In the group C, the therapy as the group B was combined on the basis of the treatment as the group A. The treatment lasted continuously for 3 menstrual cycles. The endometrial thickness, endometrial type and cervical mucus score on human chorionic gon adotropin (HCG) day, and ovulatory cycle rate, clinical pregnancy rate and abortion rate after treatment were observed in the patients of the three groups.

RESULTS1) HCG day cervical mucus score, endometrial thickness and endometrial morphology (A type rate): the results in the group C were better than those in the group A (all P<0.01); the results in the group B were better than those in the group A (all P<0.05). The difference in the endometrial thickness was not significant in comparison between the group C and the group B (P>0.05). The cervical mucus score and endometrial morphology (A type rate) in the group C were better than those in the group B (both P<0.05). 2) The ovulatory cycle rates in the group A and group (C were higher than that in the group B (both P<0.05), the pregnancy rate in the group C was higher than that in the other groups (both P<0.05), and the early abortion rate in the group C was lower than that in the group A and group B (both P<0.01). 3) Follicle diameter from 18 mm to 20 mm and endometrial thickness: the differences were not significant between the normal pregnancy patients and the early abortion patients (both P>0.05). The endometrial morphology A type rate in the normal pregnancy patients was higher than that in the early abortion patients (P<0.05).

CONCLUSIONThe combined therapy of acupuncture, herbal medicine and clomiphene improves the pregnancy rate and reduces early abortion rate by effectively improving HCG day cervical mucus, endometrial thickness and morphology. The efficacy is apparently superior to the simple medication with clomiphene and the combined application of acupuncture and herbal medicine.

Acupuncture Therapy ; Administration, Oral ; Adult ; Chorionic Gonadotropin ; metabolism ; Clomiphene ; administration & dosage ; Combined Modality Therapy ; Female ; Fertility Agents, Female ; administration & dosage ; Humans ; Infertility, Female ; drug therapy ; etiology ; metabolism ; therapy ; Moxibustion ; Polycystic Ovary Syndrome ; Pregnancy ; Pregnancy Rate ; Young Adult

No abstract available.
Clomiphene ; Humans ; Infertility* ; Male* ; Sinus Thrombosis, Intracranial*