Hormones and Thrombophilia Testing: When is it time to consider a more proactive approach to testing? 

Posted on: March 16, 2026

Elizabeth Mihal, Scientific Product Manager

Recently, it seems as if women of a certain age are inundated with ads for weighted vests and social media posts about balancing hormones. After decades of health research focusing on clinical trial data that have predominantly used male subjects, recent efforts to promote women’s health can be lauded. However, it brings with it complex issues particularly as women increasingly obtain health information online and through social media channels. These issues may be compounded further as online clinics offer easy appointments and even easier access to prescriptions, particularly for individuals who can pay out of pocket costs for prescription hormones.

The question is – when is it time to consider a more proactive approach to thrombophilia testing, particularly in women who are evaluating or re-evaluating their hormone options as they approach perimenopause and menopause?

Synthetic estrogen use has been linked to an increased incidence in thrombotic events, especially in individuals with preexisting thrombophilia risk factors. Despite this, the International Society on Thrombosis and Haemostasias (ISTH), along with other major groups like the American Society of Hematology (ASH), advise against universal thrombophilia testing before starting oral contraceptives1,2,3, but it leaves open a question as to if expanded testing might be warranted particularly as older women access estrogen to mitigate perimenopause symptoms? According to the Menopause Society, there are typically different treatment options for women in this phase. One can be oral birth control pills with an estrogen and a progestin. These have been around for a while and make use of synthetic estrogen in varying doses, which make them effective from a contraceptive standpoint but also affect blood clotting proteins in the liver.

Newer contraceptives with naturally occurring estrogens are now on the market and while early studies indicate this estrogen form should have less of an effect on coagulation proteins, there is ample opportunity for further research.

Alternatively, women can use a progestin-only birth control pill and supplement with menopause hormone therapy, a biosimilar “natural” estrogen that comes at a microdose of what is in oral birth control.4

Other options are available as well, but nearly all make use of estrogen in a population of women (i.e. age 40s+) where there exists little data on the risk of clotting events from long-term use of such therapy. Most providers advise caution in using such therapy if the patient has a history of blood clots or a condition that may increase the risk of clotting. Are there more women at risk who are unaware of their risk and if so, can a more proactive approach to thrombophilia testing be a benefit here? In some countries thrombophilia testing is routinely done in fertility clinics with all high-risk patients with the thought that, in some cases, certain treatment options can impact the likelihood of success. Perhaps this model could be used to thoroughly screen women for clot risk and provide information for shared decision-making about oral contraception and/or hormone therapy for women in their 40s and early 50s?

There will remain real questions about the utility of thrombophilia testing… assays are imperfect and even with positive test results, it may have limited impact on clinical decision making. Yet, particularly in an era of personalized medicine, are there benefits to taking a more proactive approach to testing women for thrombophilia?

A few of the common conditions that can be tested which may disproportionately affect women are proposed below. They can be defined as either hereditary or acquired conditions:

Acquired thrombophilia:

Antiphospholipid antibody panel

  • Purpose: This panel of blood tests detects three antibodies—lupus anticoagulant,anticardiolipin antibodies, and anti-beta-2-glycoprotein I antibodies—that are associatedwith antiphospholipid syndrome (APS).
  • APS is an autoimmune disorder disproportionately affecting women. A positive result usually requires confirmation with a second panel of tests at least 12 weeks later.5

Inherited thrombophilia:

Inherited thrombophilia is caused by genetic mutations that lead to deficiencies or abnormal activity of proteins involved in the clotting cascade.

Factor V Leiden (FVL) mutation –

  • Purpose: The mutation makes the Factor V protein resistant to activated protein C, which acts an inhibitor to Factor V. This can lead to a high clotting risk. Genetic testing can be performed, or many labs employ a screening assay for APC Resistance.

Prothrombin G20210A mutation –

  • Purpose: This genetic test screens for a variant in the prothrombin (Factor II) gene. If there is mutation, it leads to production of more prothrombin, which specifically increases the risk for venous thrombosis.

Protein S and C assays –

  • Purpose: Protein S and Protein C assays can be used to measure activity or antigen levelsof these proteins. These proteins work as inhibitors in the coagulation cascade to preventexcessive blood clotting. A deficiency or a defect in their function can lead to abnormal clotting.

Antithrombin III activity assay-

  • Purpose: This test assesses the activity of antithrombin III, a protein that acts as an inhibitor in the blood clotting cascade. A deficiency can be either inherited or acquired and may lead to a thrombophilic tendency.

References:

  1. Stevens, SM et. al. Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. JTH (2016) DOI 10.1007/s11239-015-1316-1
  2. Middeldorp, S et. al. American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing. Blood Adv (2023) 7 (22): 7101–7138. DOI 10.1182/bloodadvances.2023010177
  3. Blum, K. (2026, Jan) Does provoked VTE warrant thrombophilia testing? With only indirect evidence to draw on, experts offer a cautious answer: sometimes. CLN Article. https://myadlm.org/cln/articles/2026/januaryfebruary/does-provoked-vte-warrant-thrombophilia-testing
  4. Gunter, J (2025, Oct. 15) Is there a better birth control for perimenopause? A closer look at blood clots. Substack: the Vagenda. https://vajenda.substack.com/p/is-there-a-better-birth-control-pill
  5. Devreese, K MJ et. al. An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. JTH (2025) Volume 23, Issue 2, 731 – 744.
  6. Perry, DJ (2025, Jul 28) Thrombophilia Testing. Practical Hemostasis. https://practical-haemostasis.com/Thromobophilia/thrombophilia_testing_introduction.html

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