Unveiling the spectrum: A cross-sectional exploration of hirsutism causes in women

Background and Objective: Hirsutism is a common endocrine disorder and its etiology varies from benign and idiopathic disorders to serious malignant diseases. Hirsutism creates negative impact on quality of life and considerable effects on fertility. Our objective was to determine the various causes of hirsutism in women presenting at two endocrine clinics. Method: This cross-sectional study was conducted at Baqai Institute of Diabetology and Endocrinology, Karachi and at Jinnah hospital, Lahore from August 2020 to December 2021 women between 12-45 years of age with complains of hirsutism were included in the study. Severity of Hirsutism was evaluated using modified Ferriman-Gallwey score (FG). Patients with modified FG score of 8 or more were considered having hirsutism. Results: The study had 113 patients with a mean age of 15.50+7.29 years with 89% having moderate hirsutism (FG score 16-25). Polycystic ovaries was the most common cause of hirsutism. Common sites for hirsutism included back (83%), arms (74%), buttocks (70%), and upper abdomen (47%). High BMI (p-value <0.01) and high Dehydroepiandrosterone levels were positively associated with the severity of hirsutism (p-value of 0.006.) Conclusion: The various causes of hirsutism identified were polycystic ovaries, followed by idiopathic, thyroid dysfunction, congenital adrenal hyperplasia, and hyperprolactinemia; therefore, all women presenting with hirsutism should be evaluated for potential serious and curable etiologies, before embarking on a treatment plan.


INTRODUCTION
Hirsutism is the term used to describe excess terminal hair growth in females in androgen-dependent areas of the body in a pattern identical to male, affecting up to 8% of women. 1 Characteristically, it is associated with hyperandrogenemia.Most common causes of hirsutism are polycystic ovarian syndrome (PCOS) 57.7%, followed by idiopathic hirsutism 22.6%.Other causes include late onset congenital adrenal hyperplasia (CAH) 9.9%, hyperprolactinemia and thyroid disorders 4.2%.Whereas, pituitary, ovarian, and adrenal tumors are rare causes of hirsutism. 2,3Hirsutism may also be associated with obesity, insulin resistance, diabetes, hypertension, infertility, and menstrual irregularities.In Pakistan, the frequency of hirsutism is reported in 30% sub fertile females. 4irsutism, in most cases, is a relatively benign condition. 2Regardless of etiology it causes considerable emotional and psychological distress. 5Identification of serious underlying disorders is the primary purpose of laboratory testing and should be individualized.About 95% of these patients have PCOS or idiopathic hirsutism. 6,7Idiopathic hirsutism, is a term used in eumenorrheic women, who have no other clinical evidence suggesting PCOS or other hyperandrogenic endocrine disorder and is responsible for 5% to 20% cases, although some may have polycystic ovary morphology on ultrasound. 8Adrenal and ovarian neoplasms are responsible for severe cases of hirsutism.
Hirsutism severity varies according to androgen levels, it may be affected by the sensitivity of hair follicles to androgens. 6In females, the key role of androgen is to act on the body's sex-specific areas and transform small, straight, fair vellus hairs into larger, curlier, and darker terminal hairs. 9The key factors involved in the growth and development of sexual hair include Androgens such as testosterone (T), dihydrotestosterone, and prohormones like dehydroepiandrosterone sulfate (DHEAS), and androstenedione. 10Hyperandrogenemia apart from hirsutism can also exhibit as acne, menstrual dysfunction, alopecia, or it could be asymptomatic. 6irsutism classification is based on the degree of growth and distribution of hair, the most used tool for this purpose is the Ferriman-Gallwey scale. 10Androgendependent growth areas affected include the upper lip, chin, chest, upper and lower abdomen, upper arms, thighs, upper and lower back.This may be associated with other signs of virilization, including temporal balding, masculine habitus, deepening voice, clitoral hypertrophy, and amenorrhea. 11irsutism negatively influences psychological well-being, especially in young women.Diagnosis of Hirsutism is made on clinical basis as the presence of hirsutism is a potential indication of an underlying hyperandrogenic disorder that may require specific treatment and may have distinct implications for fertility, and medical risks. 5irsutism is often perceived as a cosmetic concern rather than a medically significant condition with potential serious health consequences.The purpose is to shed light on the health implications linked to hirsutism, emphasizing the need to raise awareness among individuals at risk.Hence our study aimed to determine the various causes of hirsutism in patients attending endocrine clinics at two major hospitals in Karachi and Lahore.

METHODS
This cross-sectional study was conducted at Baqai Institute of Diabetology and Endocrinology (BIDE) Karachi and Jinnah Hospital, Lahore from August 2020 to December 2021.A written informed consent was taken from participants prior to data collection and all the information acquired was kept confidential.Ethical approval: It was obtained from BIDE prior to data collection with approval # BIDE/IRB/ RTANSARI/08/20/20/0239. Inclusion criteria consists of all women between the ages of 12 to 45 years, with hirsutism (as assessed by Ferriman & Gallway score) presenting at the endocrinology clinic, were recruited by using non-probability consecutive sampling.Pregnant, & postmenopausal females were excluded from the study.A sample size of 113 was calculated using open Epi.Taking 8% 12 prevalence of hirsutism with 95% confidence level with 0.05 margin of error.
Hirsutism severity was assessed by using modified Ferriman & Gallway score. 13A cutoff of 8 and more was set for the diagnosis of hirsutism, score 8 to 15 considered as mild, 16 to 25 as moderate and more than 25 score labelled as severe hirsutism.
Imaging included ultrasound pelvis for Polycystic ovaries as well as Computed tomography of abdomen where required.

Operational definitions:
PCOs, characterized by hyperandrogenism menstrual irregularities and polycystic ovarian morphology, diagnosed based on Revised Rotterdam Criteria.CAH, a group of genetic disorders affecting the adrenal glands, resulting in abnormal production of cortisol and/ or excess androgens.
Hyperprolactinemia, elevated levels of prolactin in blood more than normal.Thyroid Disorders: hypothyroidism or hyperthyroidism were determined by deviation from normal range of TSH and T 4.
Idiopathic, where no cause was determined.Statistical analysis: All the acquired data was analyzed by using SPSS version 20.Descriptive statistics were reported in the form of mean and standard deviation for quantitative, and frequencies and percentages for qualitative variables.Chi-square test was used to determine the association between biochemical parameter and severity of hirsutism, at p-value<0.05considered as significant.

RESULTS
A total of 113 women with a mean age of 15.50+7.29 years were included in the study.The mean age of menarche was found 12.77±1.07years.Irregular menstrual cycle was reported by 77% (n7), with 13.2% (n22) had experienced amenorrhea for more than six months, 56.6% (n64) had oligomenorrhea, and 13.2% (n15) had a history of both amenorrhea and oligomenorrhea.Furthermore, 4.9% (n5) had a family history of hirsutism.The details of demographic characteristics and clinical presentation of hirsutism patients are reported in Table-I.
Association of etiology with hirsutism severity showed no significant association (Table-II).Similarly, association of BMI with etiology of hirsutism showed that hirsutism most frequently affected obese patients of PCOs, CAH and Thyroid dysfunction.Etiology of hirsutism was found significant associated BMI categories with p-value <0.01.The hormonal profile varied with the underlying pathology.Association between biochemical parameters showed that high frequencies were reported within the normal ranges of biochemical parameters levels.However, irrespective of biochemical parameters levels majority of hirsutism severity frequencies were observed in moderate category.DHEA have also showed a strong association with the severity of hirsutism with p-value 0.006 (Table-III).

DISCUSSION
In the current study, we have attempted to ascertain the predominant causes of hirsutism presenting at the study sites.The demographic analysis reveals that hirsutism is more prevalent among adolescent (15.50+7.29 years) in our population, which is similar to the finding reported by Bangladesh. 12However, other southeast Asia studies has reported a relatively older population affected by hirsutism i.e., 24 years and above. 13,14n our study the most common cause of hirsutism was polycystic ovaries (PCOs), followed by idiopathic, thyroid dysfunction, CAH, and hyperprolactinemia.6][17][18] However, etiologies like non-classic congenital adrenal hyperplasia, androgensecreting tumors, medications, hyperprolactinemia, thyroid disorders, and Cushing syndrome varied among different population. 19,20ommon clinical findings of the study revealed that majority patients experienced irregular menstrual cycles, and dyslipidemia, which was present in more than half of the women.Weight gain was reported in the majority of patients, with half of the patients falling in either class-I, or class-II obesity and a strong association of hirsutism with the BMI was reported.Hirsutism was more common in patients with increased BMI.Similar findings of 51% were reported in a study from Saudi Arabia. 21n this study mostly women were moderately hirsute, having score between 16-25 on Ferriman-Gallwey scoring.Most common body area affected by hirsutism were back, arms, buttocks, and upper abdomen.However, prior studies reported mild to moderate hirsutism and the most affected areas were face, chin, and upper lips. 22Hirsutism is the most distressing dermatological manifestation of PCOS.
Rana Tabassum Ansari et al.Studies have shown that ethnic variations in the rate of hair growth should be considered in all patients of hirsutism. 23,24Association of etiology with severity of hirsutism showed no significant difference as most participants were moderately hirsute irrespective of the cause.A Previous study done in Karachi reported varying degree of hirsutism in 47.36% of patients. 4n our study, the examination of biochemical markers revealed that most of the biochemical markers were within normal range; except, testosterone progesterone, 17OHP, and prolactin which were elevated.Association of biochemical parameter with severity of hirsutism showed that DHEA has a significant association with severity of hirsutism as patients with higher level of DHEA manifest severe hirsutism. 24mitations: The main limitation of this study pertains to the relatively small sample size, because study was confined to only two endocrine centers in Pakistan.Furthermore, the exclusive enrollment of hospitalbased presenting patients introduces a potential source of bias, limiting the generalizability of our findings to the broader population.To enhance the robustness and external validity of future investigations, we advocate for an expansion in both the scale and scope of the study.

CONCLUSION
The various causes of hirsutism were polycystic ovaries, idiopathic, thyroid dysfunction, congenital adrenal hyperplasia, and hyperprolactinemia; with PCOs being the most common cause of hirsutism among the given population.

Recommendation:
We recommend that patients with hirsutism should be evaluated thoroughly for underlying potentially curable etiologies before initiating the treatment.

Table - I
: Demographic Characteristics of Participants.

Table -
III: The Biochemical Parameter in Women with Hirsutism