Hypogonadism in females is characterized by the insufficient function of the ovaries, which leads to reduced production of germ cells (eggs) and sex hormones (estrogen and progesterone).
Primary hypogonadism occurs when there is a direct problem with the ovaries, often referred to as primary ovarian insufficiency or hypergonadotropic hypogonadism.
Secondary hypogonadism happens when there is a dysfunction in the hypothalamus or the pituitary gland, known as hypogonadotropic hypogonadism.
Factors Leading to Hypogonadism in Females
Hypogonadism in females occurs due to disturbances in any part of the hypothalamic-pituitary-ovarian axis pathway. In a properly working pathway:
- The hypothalamus starts producing gonadotropin-releasing hormone (GnRH) at the onset of puberty.
- GnRH prompts the pituitary gland to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
- FSH and LH then stimulate the ovaries to produce the hormones estrogen and progesterone.
Who Is at Risk for Hypogonadism?
Primary ovarian insufficiency and secondary hypogonadism can be either congenital, meaning individuals are born with the condition, or acquired, meaning it develops later in life due to various factors.
Congenital primary ovarian insufficiency
This often has unclear causes in many cases. However, some instances are linked to:
- Chromosomal abnormalities like Turner syndrome (45,X karyotype), fragile X syndrome, and galactosemia (a condition where the body can’t process the sugar galactose).
- Ovarian dysgenesis (abnormal development of the organ) and agenesis (when the organ fails to develop during embryonic growth).
- Congenital adrenal hyperplasia (17α-hydroxylase deficiency).
Causes of Acquired Primary Ovarian Insufficiency
- Medications such as chlorambucil, cyclophosphamide, and other alkylating agents.
- Radiotherapy.
- Autoimmune diseases, including autoimmune polyglandular syndrome type 1.
- Viral infections, such as mumps oophoritis, tuberculosis (TB), malaria, varicella.
- Bacterial infections, for example, Shigella.
- Iatrogenic disease, which may occur after surgical procedures like an oophorectomy (removal of the ovaries).
Diagnosing Hypogonadism
If hypogonadism is suspected after a thorough medical history and examination, the following steps can be taken for diagnosis:
- The patient should be referred to a specialist for further evaluation.
- Initial tests may include:
- Human chorionic gonadotropin (hCG) to rule out pregnancy
- Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
- Estradiol
- Thyroid-stimulating hormone (TSH) to check for thyroid disorders, which can cause amenorrhea
- Serum prolactin levels
- A pelvic ultrasound scan, particularly important before puberty.
Results of Hypogonadism Tests
- A positive human chorionic gonadotropin (hCG) test usually indicates pregnancy.
- If the uterus is absent or if there are other anatomical anomalies present, a karyotype test should be conducted to investigate further.
- Low or low-to-normal levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) may suggest hypogonadotropic hypogonadism. In such cases, an MRI of the brain should be considered.
- Before puberty, high levels of FSH and LH might indicate primary ovarian insufficiency. It’s important to evaluate adrenal hormones and perform a karyotype test under these circumstances.
- An elevated prolactin level should lead to consideration of an MRI to examine the pituitary gland.
Female TRT in Managing Hypogonadism Symptoms
Female Testosterone Replacement Therapy (TRT) is an emerging area of treatment for women suffering from hypogonadism where testosterone levels are affected. While traditionally associated with men, TRT can also provide benefits for women by improving symptoms such as low libido and fatigue that are often seen in hypogonadism.
It is critical to approach female TRT with careful medical guidance to tailor the therapy to the specific needs of women, considering the hormonal balance necessary for overall health.
Implementing Female TRT: Considerations and Benefits
Integrating female TRT into the treatment plan for hypogonadism involves a nuanced understanding of hormone interactions in the female body. Health practitioners must monitor the effects closely and adjust treatments as necessary to avoid potential side effects.
When effectively managed, female TRT can significantly enhance the quality of life and address specific symptoms of hypogonadism that are not typically resolved with estrogen therapy alone. This approach provides a broader spectrum of treatment that may better suit the complex nature of hormonal deficiencies in women.
Final Thoughts
Treatment for hypogonadism in females focuses on addressing the underlying cause, aiding fertility if desired, and preventing the long-term complications associated with low estrogen levels, such as osteoporosis, increased cardiovascular disease, and urogenital atrophy.
As a general guideline, women of reproductive age suffering from low estrogen should receive hormone replacement therapy. However, it’s important to consult with a specialist due to the potential significant complications of hormone therapy. These include:
Endometrial hyperplasia and carcinoma, typically prevented by adding a progestin to estrogen therapy.
Increased risk of breast cancer, venous thromboembolism, stroke, and ischemic heart disease.
After menopause, hormone replacement therapy is recommended for managing significant symptoms. Additionally, in certain cases of hypogonadism where testosterone levels are also affected, testosterone replacement therapy may be considered to improve symptoms like low libido and fatigue, ensuring a comprehensive approach to treatment.
