Prevalence of Hyperprolactinemia and Its Association with Menstrual Abnormalities and Hypothyroidism among Infertile Women: A Cross-Sectional Study from Saudi Arabia

Summary

Objectives:

To determine the prevalence of hyperprolactinemia among infertile women and assess its association with menstrual irregularities and hypothyroidism in a tertiary-care setting in Riyadh, Saudi Arabia.

Methods:

A cross-sectional study was conducted between September 2022 and August 2023 at the Reproductive Endocrinology and IVF Unit, King Abdulaziz Medical City, Riyadh. Electronic medical records of 480 infertile women who met the inclusion criteria were reviewed. Data on demographic characteristics, infertility type, thyroid status, and serum prolactin levels were collected and analyzed using SAS version 9.4. Statistical significance was set at p < 0.05.

Results:

Hyperprolactinemia was identified in 27.7% of infertile women, most commonly in the age group 31–40 years (p = 0.006). Hypothyroidism was present in 17.5% of the study population, with hyperprolactinemia observed in 22.6% of these patients (p = 0.33). Although prolactin levels significantly differed between women with regular and irregular cycles (p = 0.03), the frequency of hyperprolactinemia was similar (p = 0.44). Menstrual irregularity was more closely linked with higher BMI and LH levels.

Conclusion:

Hyperprolactinemia is a common finding among infertile women in Saudi Arabia. However, no significant association was observed between hyperprolactinemia and hypothyroidism or menstrual irregularities. Routine screening for serum prolactin levels in infertility evaluations is recommended to ensure timely diagnosis and management.

Introduction

Hyperprolactinemia remains among the most prevalent endocrine abnormalities associated with female infertility. Prolactin, secreted by the anterior pituitary, plays a pivotal role in reproductive regulation and lactation. Elevated serum prolactin disrupts the hypothalamic–pituitary–ovarian axis, leading to impaired gonadotropin release, anovulation, and infertility [1]. Clinically, hyperprolactinemia may present with menstrual irregularities, galactorrhea, or recurrent pregnancy loss, although many women remain asymptomatic [1,2].

The etiologies of hyperprolactinemia are diverse, encompassing prolactin-secreting pituitary adenomas, hypothyroidism, certain pharmacologic agents, and physiological states such as stress, sleep, or pregnancy [3,4]. The pathophysiology involves inhibition of gonadotropin-releasing hormone (GnRH), which leads to decreased secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and consequently reduced ovarian estrogen production and ovulatory dysfunction [4,5].

Recent studies continue to report variable global prevalence rates of hyperprolactinemia among infertile women, typically ranging between 10% and 35%, depending on population characteristics and diagnostic criteria [2,6]. Several recent studies have reaffirmed the coexistence of hyperprolactinemia and thyroid dysfunction, particularly subclinical hypothyroidism, suggesting shared hypothalamic–pituitary regulatory pathways [7]. Furthermore, menstrual irregularities and amenorrhea have been widely reported in women with hyperprolactinemia, reflecting its impact on gonadal function [8]. However, these findings have been inconsistent across populations and geographic regions.

Despite robust international literature, few studies have examined hyperprolactinemia among infertile women in Saudi Arabia. Characterizing its local prevalence and clinical correlates is essential for optimizing reproductive endocrinology practice in the region.

Therefore, this study aimed to determine the prevalence of hyperprolactinemia among infertile women attending a tertiary hospital in Riyadh, Saudi Arabia, and to evaluate its association with menstrual abnormalities and hypothyroidism.

Methods

This cross-sectional, record-based study was conducted between September 2022 and August 2023 at the Reproductive Endocrinology and IVF Unit, Women's Health Hospital, King Abdulaziz Medical City, Riyadh, Saudi Arabia. The ethical approval was obtained from the King Abdullah International Medical Research Center Institutional Review Board (KAIMRC-IRB No. SP22R/089/05). The study used anonymized retrospective data; therefore, informed consent was waived. All data were de-identified, stored in a password-protected file, and accessed only by the research team. The study investigated the prevalence of hyperprolactinemia among infertile women and its association with menstrual irregularities and hypothyroidism. All eligible women presenting to the infertility clinic during the study period were consecutively included using a non-probability (purposive) sampling method. Inclusion criteria were women <40 years of age, body-mass index (BMI) <40 kg/m², parity ≤ 3, and normal day-2 serum FSH levels. While the exclusion criteria were women >40 years of age, BMI ≥40 kg/m², abnormal FSH levels, parity >3, or those undergoing assisted reproductive therapy for indications other than infertility.

The sample size was estimated using Raosoft® software with a 95% confidence level, 5% margin of error, and an assumed prevalence of 50% (no prior Saudi data available). The required sample size was 385 patients; data from 480 eligible women were included, providing adequate statistical power.

Data were extracted from the hospital's BESTCare electronic health record system using a standardized chart review form developed by the research team: i) Demographic variables: age, BMI, parity. ii) Clinical variables: type and duration of infertility (primary/secondary), menstrual-cycle regularity, and ovulation status. iiI) Laboratory parameters: serum prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol levels, and thyroid-stimulating hormone (TSH). Serum-prolactin concentrations were categorized as hypoprolactinemia (<2 ng/mL), normal (2–25 ng/mL), or hyperprolactinemia (>25 ng/mL).

The primary outcome was the prevalence of hyperprolactinemia among infertile women.

Secondary outcomes included the association of hyperprolactinemia with menstrual-cycle regularity and with thyroid-function status (hypothyroidism or hyperthyroidism).

Statistical analysis

All statistical analyses were performed using SAS software, version 9.4 (SAS Institute Inc., Cary, NC, USA). Descriptive statistics were used to summarize the data: categorical variables were presented as frequencies and percentages, and continuous variables as mean ± standard deviation (SD) or median (interquartile range) where appropriate. Normality of continuous data was assessed using the Shapiro–Wilk test. Assumptions of normality and homogeneity of variance were verified using the Shapiro–Wilk and Levene's tests.

Differences between groups were examined using the chi-square or Fisher's exact test for categorical variables and the independent Student's t-test for continuous variables. Variables with a p-value < 0.10 in univariate analysis were entered into a multivariate logistic regression model using stepwise backward elimination to identify independent predictors of hyperprolactinemia. Results were reported as adjusted odds ratios (ORs) with 95% confidence intervals (CIs).

All p-values were 2-tailed, and a p-value <0.05 was considered statistically significant. The study was reported in accordance with the STROBE statement for cross-sectional studies.

Results

Participant characteristics

All 480 infertile women were included in the final analysis with no missing data. The mean age was 32.6 ± 4.5 years (range = 22–40 years). Most participants were aged 31–40 years (67.9%) and had either overweight or obesity (73.6%). Primary and secondary infertility were nearly equal in frequency (50.4% and 49.6%, respectively). Regular menstrual cycles were reported by 80.4% of women, and ovulation was confirmed in 76.5%. Hyperprolactinemia was detected in 27.7% of participants, hypoprolactinemia in 3.8%, and normal prolactin levels in 68.5%. Regarding thyroid status, 17.5% were hypothyroid, 2.9% hyperthyroid, and 79.6% euthyroid (Table 1).

Table 1.

Baseline characteristics of infertile women (N = 480).

Variable	n (%)
Age ≤30 years	154 (32.1%)
Age 31–40 years	326 (67.9%)
BMI (kg/m2), mean±SD	28.7 ± 5.2
Underweight	11 (2.3%)
Normal weight	116 (24.2%)
Overweight	159 (33.1%)
Obese	194 (40.4%)
Infertility type: Primary	242 (50.4%)
Infertility type: Secondary	238 (49.6%)
Menstrual regularity: Regular	386 (80.4%)
Menstrual regularity: Irregular	94 (19.6%)
Ovulation confirmed	367 (76.5%)
Hyperprolactinemia	133 (27.7%)
Hypoprolactinemia	18 (3.8%)
Normal prolactin	329 (68.5%)
Hypothyroidism	84 (17.5%)
Hyperthyroidism	14 (2.9%)
Euthyroid	382 (79.6%)

Sd: standard deviation.

Prevalence and clinical correlates of hyperprolactinemia

Among the 480 infertile women, 133 (27.7%) had hyperprolactinemia. It occurred most frequently in the 31–40-year (61.7%) age group compared with women aged ≤ 30 (38.3%) years, showing a statistically significant difference (p = 0.006). No significant associations were found between prolactin status and BMI (p = 0.17), ovulation (p = 0.66), or thyroid function (p = 0.28). Mean prolactin concentration was markedly higher in the hyperprolactinemic group (777.4 ± 394.8 ng/mL) than in women with normal prolactin levels (326.4 ± 108.6 ng/mL, p < 0.001). Infertility type was significantly related to prolactin status, with primary infertility observed more often in hyperprolactinemic women (61.7% vs 45.6%, p = 0.006) (Table 2).

Table 2.

Association between prolactin status and clinical variables.

Variable	Hyperprolactinemia (n = 133)	Normal (n = 329)	Hypoprolactinemia (n = 18)	P-value
Age ≤30 years	38.3%	29.8%	27.8%	0.006
Age 31–40 years	61.7%	70.2%	72.2%
BMI (kg/m2)	29.0 ± 5.0	28.5 ± 5.3	28.7 ± 5.1	0.17
Primary infertility	61.7%	45.6%	55.6%	0.006
Secondary infertility	38.3%	54.4%	44.4%
Menstrual irregularity	15.8%	21.0%	22.2%	0.44
Regular cycle	84.2%	79.0%	77.8%
Mean prolactin (ng/mL)	777.4 ± 394.8	326.4 ± 108.6	42.7 ± 31.2	<0.001

Association between hypothyroidism and clinical variables

Hypothyroidism was identified in 84 women (17.5%). The mean prolactin level among hypothyroid participants (412.5 ± 278.5 ng/mL) did not differ significantly from that of euthyroid (445.4 ± 320.5 ng/mL) or hyperthyroid women (480.8 ± 280.6 ng/mL, p = 0.33). However, the mean duration of infertility was significantly longer among hypothyroid women (76.8 ± 52.2 months) compared with euthyroid women (56.8 ± 40.3 months, p = 0.004). Thyroid status was strongly associated with TSH concentrations (p < 0.001) (Table 3).

Table 3.

Association between thyroid status, menstrual regularity, and selected hormones.

Variable	Hypothyroidism (n = 84)	Euthyroid (n = 382)	Hyperthyroidism (n = 14)	p-value
Infertility duration (months)	76.8 ± 52.2	56.8 ± 40.3	48.3 ± 32.5	0.004
Prolactin (ng/mL)	412.5 ± 278.5	445.4 ± 320.5	480.8 ± 280.6	0.33
TSH (mIU/L)	3.35 ± 2.54	2.31 ± 1.16	7.01 ± 7.71	<0.001
BMI (kg/m2)	29.1 ± 5.1	28.5 ± 5.3	29.3 ± 5.4	0.30
Menstrual irregularity (%)	27.4%	17.3%	35.7%	0.03
LH (IU/L)	4.57 ± 2.98	4.63 ± 3.21	4.86 ± 2.61	0.003

BMI: body mass index, TSH: thyroid-stimulating hormone.

Association between menstrual regularity and hormonal parameters

Menstrual irregularities were reported in 94 (19.6%) women. Women with irregular cycles had significantly higher BMI values (p = 0.002) and elevated serum LH concentrations (p = 0.003) compared with those with regular cycles. Mean prolactin levels differed significantly between the 2 groups (393.9 ± 266.7 ng/mL vs 452.1 ± 321.6 ng/mL, p = 0.03); however, the frequency of hyperprolactinemia was not significantly different (22.3% vs 29%, p = 0.44). These findings indicate that menstrual irregularities are more strongly associated with BMI and LH variations than with prolactin status (Table 3).

Discussion

This study evaluated the prevalence of hyperprolactinemia among infertile women and explored its association with menstrual irregularities and thyroid dysfunction in a tertiary hospital in Riyadh, Saudi Arabia. Hyperprolactinemia was detected in 27.7% of the study population, with the highest frequency observed among women aged 31–40 years and those presenting with primary infertility. However, no statistically significant associations were observed between hyperprolactinemia and either hypothyroidism or menstrual-cycle irregularities.

Prevalence of hyperprolactinemia

The prevalence identified in this cohort aligns with recent international findings, where hyperprolactinemia among infertile women has been reported in 20–35% of cases [2,5,6]. Differences across studies likely reflect variations in population characteristics, diagnostic thresholds, and prolactin assay techniques. Comparable rates have been documented in recent studies from Mexico and India, which similarly emphasized hyperprolactinemia as a frequent cause of anovulatory infertility [5,6]. Our finding that the condition was most common among women aged 31–40 years may be attributed to delayed fertility consultation or cumulative environmental, psychological, and metabolic stressors affecting pituitary function. This age-related distribution is consistent with evidence suggesting that prolonged exposure to physiological or pharmacologic factors can influence prolactin secretion and reproductive outcomes [1,3,4].

Association with hypothyroidism

Although hypothyroidism is a recognized secondary cause of hyperprolactinemia due to thyrotropin-releasing hormone (TRH) stimulation of prolactin secretion, our results did not demonstrate a significant relationship between these 2 conditions. Recent studies also report inconsistent associations, with several showing no significant correlation between serum TSH and prolactin levels after correction for confounding factors [7]. This lack of association may reflect early diagnosis and adequate management of thyroid disorders in our population, leading to normalization of prolactin levels before infertility evaluation. Additionally, subclinical hypothyroidism may exert only minimal influence on prolactin secretion, as supported by van der Ham et al. [7], who demonstrated that mild thyroid dysfunction in reproductive-age women often does not translate into clinically meaningful hyperprolactinemia. This is also supported by a 2025 meta-analysis which describes subclinical hypothyroidism as the most reported thyroid disorder in hyperprolactinemia [9].

Association with menstrual irregularities

In our study, mean prolactin levels differed significantly between women with regular and irregular menstrual cycles (p = 0.03), yet the overall frequency of hyperprolactinemia did not vary between the 2 groups. This suggests that mild prolactin elevations may not always manifest as menstrual disturbances and that other hormonal imbalances may modulate cycle regularity. Recent research indicates that the relationship between prolactin and menstrual abnormalities is nonlinear and may depend on both the degree and duration of prolactin elevation as well as coexisting conditions such as polycystic ovary syndrome [1,2,6]. These findings support the view that reproductive dysfunction in hyperprolactinemic women arises from multifactorial mechanisms involving not only prolactin excess but also alterations in gonadotropin and thyroid signaling pathways [1,4]. Interestingly, women with irregular cycles also exhibited higher BMI and LH levels, suggesting that metabolic and gonadotropic factors may contribute to menstrual disturbances independent of prolactin levels.

Clinical implications

Given that more than one-quarter of infertile women in our cohort exhibited hyperprolactinemia, the inclusion of serum prolactin testing in routine infertility evaluation remains essential in Saudi Arabia. Early detection and treatment with dopamine agonists can restore ovulation and significantly improve pregnancy rates [1,4]. Moreover, simultaneous assessment of thyroid function is warranted to exclude secondary causes and to ensure comprehensive endocrine evaluation. Although our study did not find a significant association between hyperprolactinemia and hypothyroidism, screening for both conditions enables timely identification of overlapping endocrine disorders that may impair fertility. Additionally, recognizing the influence of body weight and LH variability on menstrual regularity may guide more individualized management strategies for infertile women.

Study strengths and limitations

This study has several strengths, including a relatively large sample size (n = 480) and the use of validated electronic medical records, which enhance data completeness, reliability, and internal validity within a tertiary care setting. However, some limitations should be taken into consideration. First, the ability to determine the casual inference between hyperprolactinemia and infertility outcome is limited by the cross-sectional nature of the study. Second, the study was conducted in a single center setting, which might limit the generalizability to a broader population. Third, the retrospective design restricted control of potential confounders. Finally, pituitary imaging was not routinely available, preventing differentiation between functional and structural causes of hyperprolactinemia. Future multicenter prospective studies incorporating repeated hormonal measurements and neuroimaging are warranted.

The study was approved by the King Abdullah International Medical Research Center Institutional Review Board (KAIMRC-IRB No. SP22R/089/05). The study used anonymized retrospective data; therefore, informed consent was waived. All collected data were kept confidential and accessed only by the research team.

In conclusion, approximately one in 4 infertile women in this Saudi cohort exhibited hyperprolactinemia, most commonly among those aged 31–40 years and with primary infertility. No significant associations were observed between hyperprolactinemia and hypothyroidism or menstrual irregularities. Routine prolactin screening should be incorporated into infertility workups to facilitate early diagnosis and management, alongside comprehensive endocrine evaluation.

Further prospective multicenter studies are needed to explore the underlying mechanisms and long-term reproductive outcomes associated with hyperprolactinemia in Saudi women.

Acknowledgement

The authors would like to thank LANGVARA Translation and Proofreading Services (langvara.com) for English language editing and proofreading of the manuscript.

Disclosure

The authors declare no conflict of interest. The study received no external funding and was not supported by any drug company. The authors declare that no artificial intelligence tools were used in the writing of the manuscript, the creation of figures or images, or the collection and analysis of data. The authors declare that this work has not been presented at any conference, and no abstract from this study has been published in conference proceedings or journal supplements.